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New definitions of hypertension reveal new preeclampsia risks
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
according to results from a large retrospective cohort study.
In a 2017 guideline, the American College of Cardiology and American Heart Association changed clinical definitions of hypertension in adults. People previously deemed to have prehypertension were classed as having elevated blood pressure (systolic BP 120-129 mm Hg and diastolic BP >80 mm Hg) or stage 1 hypertension (systolic 130-139 mm Hg or diastolic 80-89 mm Hg).
And while hypertension as earlier defined (at or above systolic 140 mm Hg or at or above diastolic 90 mm Hg; now called stage 2 hypertension) has been long associated with adverse maternal and fetal effects, it was unclear whether lesser elevations in blood pressure also are linked to the same.
For their research published in Obstetrics & Gynecology, Elizabeth F. Sutton, PhD, of the University of Pittsburgh and colleagues looked at records from 18,162 women who had given birth to a single baby and had two or more prenatal appointments before week 20 of pregnancy. The women in the study were seen at the same institution over a 3-year period ending in 2018. Three-quarters of the cohort had normal blood pressure, while 14% had elevated blood pressure and 5% had stage 1 hypertension before 20 weeks. Another 6% of the cohort had stage 2 hypertension.
The authors found preeclampsia risk increased with increasing blood pressure elevation. Among women with normal blood pressure before 20 weeks’ gestation, 5% had preeclampsia, while 7% of those with elevated blood pressure did, as did with 12% of women with stage 1 hypertension and 30% of women with stage 2 hypertension. The increase in risk of preeclampsia was because of preterm preeclampsia in the women with elevated blood pressure. Both term and preterm preeclampsia were factors in women with stage 1 and stage 2 hypertension, but preterm preeclampsia was associated with a higher risk. Although black race was associated with a higher risk of preeclampsia, the pattern of increasing risk with higher blood pressure category was similar in both black and white women.
Researchers also looked at gestational diabetes, severe maternal morbidity, neonatal morbidity, and placental abruption as secondary outcomes. They found the risk of gestational diabetes increased in a stepwise fashion as blood pressure increased, compared with normotensive women. Higher risk of severe maternal and neonatal morbidities was seen only in women with stage 2 hypertension. Placental abruption was rare in this cohort and the odds were not increased in any group.
The findings “highlight the importance of early pregnancy BP elevations, which may reflect prepregnancy BP status,” and suggest that the new guidelines “can identify women early in pregnancy who may benefit from increased surveillance,” Dr. Sutton and colleagues wrote.
Although randomized trials will be needed to identify the best prevention and management strategies for this patient group, they added, some clinicians may want to consider low-dose aspirin – an intervention shown to safely reduce preeclampsia risk among women with stage 2 hypertension – for women with elevated BP or stage 1 hypertension.
Dr. Sutton and colleagues acknowledged that its retrospective design is among the limitations of their study, and that use of antihypertensive medications could not be captured in their study.
Preeclampsia researcher Mark Santillan, MD, PhD, of the University of Iowa in Iowa City, said in an interview that the results “open the door to considering these new blood pressure categories as a prognosticator” for preeclampsia. “This paper furthers the field by applying these new categories to hypertensive diseases in pregnancy which are not well studied” in comparison to nonpregnant hypertensive states.
“Are these seemingly normal blood pressures associated with poor outcomes, maternal or neonatal? I think that this paper strongly tells us yes,” Dr. Santillan added. “But does that mean we have to do more aggressive blood pressure monitoring, seeing your doctor every month or so? Maybe we should change the way we’re treating people early on in gestation.”
The question of whether aspirin helps reduce preeclampsia risk in women with elevated blood pressure or stage 1 hypertension needs to be resolved in studies, Dr. Santillan said. But because of its favorable risk profile, “if I consider that if a patient has significant risk factors for developing preeclampsia, baby aspirin is fine.”
Postpregnancy blood pressure management is something that should also be reconsidered in light of the findings, Dr. Santillan said. Half of women with preeclampsia will have chronic hypertension after they deliver, increasing their risk of adverse cardiovascular outcomes later in life. But because most are young and otherwise healthy, they often are lost to follow-up.
“I think this paper has helped open up that conversation, that there is probably a link between what we’re doing in pregnancy to what we should be doing in the postpartum period,” he said.
Dr. Sutton and colleagues’ study received funding from the Richard King Mellon Foundation, the American Heart Association; and the National Institutes of Health. None of its authors had relevant disclosures. Dr. Santillan disclosed holding U.S. and international patents for preeclampsia prediction, diagnosis, and treatment.
SOURCE: Sutton et al. Obstet Gynecol. 2020;136:129-39.
FROM OBSTETRICS & GYNECOLOGY
Dairy doesn’t do a body good in midlife women
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Disparate study results on elective labor costs fuel debate
Cost concerns have circulated regarding elective induction of labor, a method that’s become increasingly popular in the United States. Two studies in Obstetrics & Gynecology, however, offer no consensus on the cost burden of this method.
A retrospective analysis of a large cohort in California reported higher costs for induction, compared with spontaneous labor, after accounting for variables such as parity, mode of delivery, and gestational age. A prospective study of five Utah hospitals found no significant cost differences between induction and expectant management.
The ARRIVE trial (A Randomized Trial of Induction versus Expectant Management), a multicenter study that compared elective labor induction at 39 weeks of gestation with spontaneous labor in low-risk nulliparous women, suggests that induction may have some benefits. While its researchers found no differences in perinatal outcomes, induction cases had fewer cesareans, fewer hypertensive disorders, and fewer newborns requiring respiratory support.
One key question that remains following ARRIVE is whether this practice should be implemented universally, Alyssa R. Hersh, MD, MPH, lead author of the California study, said in an interview. Quantifying the costs associated with elective labor is important because “health care in the United States is already much more expensive than in other countries, and [elective labor] could have a dramatic impact on annual health care costs.”
In a retrospective analysis, Dr. Hersh, of the Oregon Health & Science University, Portland, and her colleagues examined data from more than 1.2 million women in California with singleton, nonanomalous births. They excluded for multiple factors such as medically indicated induction of labor, placenta previa, breech presentation, or planned cesarean delivery.
Estimating cost differences between elective induction and spontaneous labor for mothers and neonates, they stratified results by vaginal or cesarean delivery, parity, gestational age at delivery, and geographic location. Elective induced labor represented 15% of the overall cohort of 1.2 million women.
Among vaginal deliveries, median maternal hospitalization costs were $10,175 in the induction group and $9,462 in the spontaneous labor group. For cesarean deliveries, the median costs were $20,294 with induction of labor and $18,812 with spontaneous labor.
Costs of maternal hospitalization with elective induction of labor were significantly higher than that of spontaneous labor, regardless of parity, mode of delivery, and gestational age at delivery, the authors reported. Comparing costs at rural and urban areas, the induction group saw higher maternal hospitalization costs and longer lengths of stay regardless of scenario.
Neonatal care was the one metric that incurred lower costs and lengths of stay in the induction group. Fewer adverse outcomes in this group could explain this outlier. “However, because this is observational data, we cannot elucidate what exactly contributed to these decreased costs,” Dr. Hersh and colleagues noted.
Timeliness was another limitation. “It is important to note that our study was conducted between 2007 and 2011, and the patients undergoing elective induction of labor during those years may differ from women undergoing elective induction of labor currently,” the authors acknowledged.
Another study by Brett D. Einerson, MD, MPH, of the University of Utah Health, Salt Lake City, and associates evaluated the actual hospital costs of patients undergoing elective induction and expectant management in a subset of patients from the ARRIVE trial.
“If, medically speaking, induction is equal to expectant management or has some benefit, as the larger ARRIVE trial suggests, we wanted to know: At what cost?” Dr. Einerson said in an interview.
Study participants hailed from five Utah hospitals within two health systems: the University of Utah Health and Intermountain Healthcare. Taking available data for 1,231 enrollees, investigators randomized 608 to labor induction and 623 to spontaneous labor. They measured actual hospital costs using advanced value-based analytics platforms at the Utah hospitals, comparing cost means and reporting the relative difference between induction and expectant management.
Overall, they found no significant differences between the mean total cost of elective induction and expectant management (adjusted mean difference, +4.7%). This was the case for other metrics: Costs did not vary among the five health systems or in most phases of care, including maternal inpatient postpartum care, maternal outpatient care after discharge, neonatal hospital care, and neonatal care after discharge.
The induction group did incur higher maternal inpatient intrapartum and delivery care costs (17%). However, these were offset by savings achieved during outpatient antenatal care (–47%). The assumption was additional costs of time spent on the labor ward might overwhelm cost savings elsewhere (reduced cesarean deliveries, fewer prenatal appointments and tests). “But this was not the case,” Dr. Einerson said.
Ultimately, the study was not large enough to find smaller differences in cost, he noted. It was only large enough to say that cost didn’t differentiate between arms with a margin of +/–7%. “A cost increase (or cost savings) with induction of 7% is meaningful over time and on a national scale,” Dr. Einerson explained.
Taken together, the two studies show that cost is not an insurmountable barrier to elective induced labor, Jeffrey L. Ecker, MD, and Mark A. Clapp, MD, MPH, wrote in an accompanying editorial (Obstet Gynecol. 2020;136[1]:6-7).
“This will be especially true if we are innovative and creatively adapt our facilities and spaces, thinking about where and how some of the required care can be appropriately and more economically offered,” they noted.
“Specifically, strategies to safely reduce labor and delivery time for inductions of labor, including considering and studying outpatient cervical ripening, may make elective induction of labor at 39 weeks of gestation even less costly and even more feasible to offer to all women,” suggested Dr. Ecker and Dr. Clapp, both at Massachusetts General Hospital and Harvard Medical School, both in Boston.
Dr. Hersh and coauthors had no relevant financial disclosures, and there was no external funding for their study. Dr. Einerson and most coauthors reported no relevant financial disclosures; one coauthor reported receiving funds from GestVision as a consultant, and another coauthor reported funds paid to her or her institution from some pharmaceutical companies when she was primary investigator on various trials or a consultant. This study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Neither Dr. Ecker nor Dr Clapp had any relevant financial disclosures or received any funding.
SOURCES: Hersh AR et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003865; Einerson BD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003930.
Cost concerns have circulated regarding elective induction of labor, a method that’s become increasingly popular in the United States. Two studies in Obstetrics & Gynecology, however, offer no consensus on the cost burden of this method.
A retrospective analysis of a large cohort in California reported higher costs for induction, compared with spontaneous labor, after accounting for variables such as parity, mode of delivery, and gestational age. A prospective study of five Utah hospitals found no significant cost differences between induction and expectant management.
The ARRIVE trial (A Randomized Trial of Induction versus Expectant Management), a multicenter study that compared elective labor induction at 39 weeks of gestation with spontaneous labor in low-risk nulliparous women, suggests that induction may have some benefits. While its researchers found no differences in perinatal outcomes, induction cases had fewer cesareans, fewer hypertensive disorders, and fewer newborns requiring respiratory support.
One key question that remains following ARRIVE is whether this practice should be implemented universally, Alyssa R. Hersh, MD, MPH, lead author of the California study, said in an interview. Quantifying the costs associated with elective labor is important because “health care in the United States is already much more expensive than in other countries, and [elective labor] could have a dramatic impact on annual health care costs.”
In a retrospective analysis, Dr. Hersh, of the Oregon Health & Science University, Portland, and her colleagues examined data from more than 1.2 million women in California with singleton, nonanomalous births. They excluded for multiple factors such as medically indicated induction of labor, placenta previa, breech presentation, or planned cesarean delivery.
Estimating cost differences between elective induction and spontaneous labor for mothers and neonates, they stratified results by vaginal or cesarean delivery, parity, gestational age at delivery, and geographic location. Elective induced labor represented 15% of the overall cohort of 1.2 million women.
Among vaginal deliveries, median maternal hospitalization costs were $10,175 in the induction group and $9,462 in the spontaneous labor group. For cesarean deliveries, the median costs were $20,294 with induction of labor and $18,812 with spontaneous labor.
Costs of maternal hospitalization with elective induction of labor were significantly higher than that of spontaneous labor, regardless of parity, mode of delivery, and gestational age at delivery, the authors reported. Comparing costs at rural and urban areas, the induction group saw higher maternal hospitalization costs and longer lengths of stay regardless of scenario.
Neonatal care was the one metric that incurred lower costs and lengths of stay in the induction group. Fewer adverse outcomes in this group could explain this outlier. “However, because this is observational data, we cannot elucidate what exactly contributed to these decreased costs,” Dr. Hersh and colleagues noted.
Timeliness was another limitation. “It is important to note that our study was conducted between 2007 and 2011, and the patients undergoing elective induction of labor during those years may differ from women undergoing elective induction of labor currently,” the authors acknowledged.
Another study by Brett D. Einerson, MD, MPH, of the University of Utah Health, Salt Lake City, and associates evaluated the actual hospital costs of patients undergoing elective induction and expectant management in a subset of patients from the ARRIVE trial.
“If, medically speaking, induction is equal to expectant management or has some benefit, as the larger ARRIVE trial suggests, we wanted to know: At what cost?” Dr. Einerson said in an interview.
Study participants hailed from five Utah hospitals within two health systems: the University of Utah Health and Intermountain Healthcare. Taking available data for 1,231 enrollees, investigators randomized 608 to labor induction and 623 to spontaneous labor. They measured actual hospital costs using advanced value-based analytics platforms at the Utah hospitals, comparing cost means and reporting the relative difference between induction and expectant management.
Overall, they found no significant differences between the mean total cost of elective induction and expectant management (adjusted mean difference, +4.7%). This was the case for other metrics: Costs did not vary among the five health systems or in most phases of care, including maternal inpatient postpartum care, maternal outpatient care after discharge, neonatal hospital care, and neonatal care after discharge.
The induction group did incur higher maternal inpatient intrapartum and delivery care costs (17%). However, these were offset by savings achieved during outpatient antenatal care (–47%). The assumption was additional costs of time spent on the labor ward might overwhelm cost savings elsewhere (reduced cesarean deliveries, fewer prenatal appointments and tests). “But this was not the case,” Dr. Einerson said.
Ultimately, the study was not large enough to find smaller differences in cost, he noted. It was only large enough to say that cost didn’t differentiate between arms with a margin of +/–7%. “A cost increase (or cost savings) with induction of 7% is meaningful over time and on a national scale,” Dr. Einerson explained.
Taken together, the two studies show that cost is not an insurmountable barrier to elective induced labor, Jeffrey L. Ecker, MD, and Mark A. Clapp, MD, MPH, wrote in an accompanying editorial (Obstet Gynecol. 2020;136[1]:6-7).
“This will be especially true if we are innovative and creatively adapt our facilities and spaces, thinking about where and how some of the required care can be appropriately and more economically offered,” they noted.
“Specifically, strategies to safely reduce labor and delivery time for inductions of labor, including considering and studying outpatient cervical ripening, may make elective induction of labor at 39 weeks of gestation even less costly and even more feasible to offer to all women,” suggested Dr. Ecker and Dr. Clapp, both at Massachusetts General Hospital and Harvard Medical School, both in Boston.
Dr. Hersh and coauthors had no relevant financial disclosures, and there was no external funding for their study. Dr. Einerson and most coauthors reported no relevant financial disclosures; one coauthor reported receiving funds from GestVision as a consultant, and another coauthor reported funds paid to her or her institution from some pharmaceutical companies when she was primary investigator on various trials or a consultant. This study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Neither Dr. Ecker nor Dr Clapp had any relevant financial disclosures or received any funding.
SOURCES: Hersh AR et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003865; Einerson BD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003930.
Cost concerns have circulated regarding elective induction of labor, a method that’s become increasingly popular in the United States. Two studies in Obstetrics & Gynecology, however, offer no consensus on the cost burden of this method.
A retrospective analysis of a large cohort in California reported higher costs for induction, compared with spontaneous labor, after accounting for variables such as parity, mode of delivery, and gestational age. A prospective study of five Utah hospitals found no significant cost differences between induction and expectant management.
The ARRIVE trial (A Randomized Trial of Induction versus Expectant Management), a multicenter study that compared elective labor induction at 39 weeks of gestation with spontaneous labor in low-risk nulliparous women, suggests that induction may have some benefits. While its researchers found no differences in perinatal outcomes, induction cases had fewer cesareans, fewer hypertensive disorders, and fewer newborns requiring respiratory support.
One key question that remains following ARRIVE is whether this practice should be implemented universally, Alyssa R. Hersh, MD, MPH, lead author of the California study, said in an interview. Quantifying the costs associated with elective labor is important because “health care in the United States is already much more expensive than in other countries, and [elective labor] could have a dramatic impact on annual health care costs.”
In a retrospective analysis, Dr. Hersh, of the Oregon Health & Science University, Portland, and her colleagues examined data from more than 1.2 million women in California with singleton, nonanomalous births. They excluded for multiple factors such as medically indicated induction of labor, placenta previa, breech presentation, or planned cesarean delivery.
Estimating cost differences between elective induction and spontaneous labor for mothers and neonates, they stratified results by vaginal or cesarean delivery, parity, gestational age at delivery, and geographic location. Elective induced labor represented 15% of the overall cohort of 1.2 million women.
Among vaginal deliveries, median maternal hospitalization costs were $10,175 in the induction group and $9,462 in the spontaneous labor group. For cesarean deliveries, the median costs were $20,294 with induction of labor and $18,812 with spontaneous labor.
Costs of maternal hospitalization with elective induction of labor were significantly higher than that of spontaneous labor, regardless of parity, mode of delivery, and gestational age at delivery, the authors reported. Comparing costs at rural and urban areas, the induction group saw higher maternal hospitalization costs and longer lengths of stay regardless of scenario.
Neonatal care was the one metric that incurred lower costs and lengths of stay in the induction group. Fewer adverse outcomes in this group could explain this outlier. “However, because this is observational data, we cannot elucidate what exactly contributed to these decreased costs,” Dr. Hersh and colleagues noted.
Timeliness was another limitation. “It is important to note that our study was conducted between 2007 and 2011, and the patients undergoing elective induction of labor during those years may differ from women undergoing elective induction of labor currently,” the authors acknowledged.
Another study by Brett D. Einerson, MD, MPH, of the University of Utah Health, Salt Lake City, and associates evaluated the actual hospital costs of patients undergoing elective induction and expectant management in a subset of patients from the ARRIVE trial.
“If, medically speaking, induction is equal to expectant management or has some benefit, as the larger ARRIVE trial suggests, we wanted to know: At what cost?” Dr. Einerson said in an interview.
Study participants hailed from five Utah hospitals within two health systems: the University of Utah Health and Intermountain Healthcare. Taking available data for 1,231 enrollees, investigators randomized 608 to labor induction and 623 to spontaneous labor. They measured actual hospital costs using advanced value-based analytics platforms at the Utah hospitals, comparing cost means and reporting the relative difference between induction and expectant management.
Overall, they found no significant differences between the mean total cost of elective induction and expectant management (adjusted mean difference, +4.7%). This was the case for other metrics: Costs did not vary among the five health systems or in most phases of care, including maternal inpatient postpartum care, maternal outpatient care after discharge, neonatal hospital care, and neonatal care after discharge.
The induction group did incur higher maternal inpatient intrapartum and delivery care costs (17%). However, these were offset by savings achieved during outpatient antenatal care (–47%). The assumption was additional costs of time spent on the labor ward might overwhelm cost savings elsewhere (reduced cesarean deliveries, fewer prenatal appointments and tests). “But this was not the case,” Dr. Einerson said.
Ultimately, the study was not large enough to find smaller differences in cost, he noted. It was only large enough to say that cost didn’t differentiate between arms with a margin of +/–7%. “A cost increase (or cost savings) with induction of 7% is meaningful over time and on a national scale,” Dr. Einerson explained.
Taken together, the two studies show that cost is not an insurmountable barrier to elective induced labor, Jeffrey L. Ecker, MD, and Mark A. Clapp, MD, MPH, wrote in an accompanying editorial (Obstet Gynecol. 2020;136[1]:6-7).
“This will be especially true if we are innovative and creatively adapt our facilities and spaces, thinking about where and how some of the required care can be appropriately and more economically offered,” they noted.
“Specifically, strategies to safely reduce labor and delivery time for inductions of labor, including considering and studying outpatient cervical ripening, may make elective induction of labor at 39 weeks of gestation even less costly and even more feasible to offer to all women,” suggested Dr. Ecker and Dr. Clapp, both at Massachusetts General Hospital and Harvard Medical School, both in Boston.
Dr. Hersh and coauthors had no relevant financial disclosures, and there was no external funding for their study. Dr. Einerson and most coauthors reported no relevant financial disclosures; one coauthor reported receiving funds from GestVision as a consultant, and another coauthor reported funds paid to her or her institution from some pharmaceutical companies when she was primary investigator on various trials or a consultant. This study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Neither Dr. Ecker nor Dr Clapp had any relevant financial disclosures or received any funding.
SOURCES: Hersh AR et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003865; Einerson BD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003930.
Liposomal bupivacaine excreted in breast milk, but levels appear safe
based on a prospective cohort study.
Over the course of 4 days, relative neonatal dosages of bupivacaine were less than 1%, remaining below the 10% threshold of concern, reported Hiba J. Mustafa, MD, of the University of Minnesota, Minneapolis, and colleagues.
Liposomal bupivacaine can achieve up to 4 days of postcesarean pain control, which is significantly longer than the 8 hours provided by standard bupivacaine, the investigators wrote in Obstetrics & Gynecology. But usage of the liposomal formulation has not been widespread, they noted, partly because of a lack of clinical studies evaluating breast milk transfer and neonatal safety.
To address this knowledge gap, Dr. Mustafa and colleagues enrolled 30 healthy pregnant women scheduled to undergo cesarean birth at full term. All patients were aged 18-40 years, with an American Society of Anesthesiologists physical status of I or II. Exclusion criteria included a number of maternal and neonatal health concerns, such as sensitivity to local anesthetics, metabolic disorders, fetal anomaly, fetal growth restriction, and others.
The day of surgery, before the procedure, maternal blood samples were collected and used for baseline measurements.
Each woman received a spinal anesthetic including 150 mcg of morphine, 15 mcg of intrathecal fentanyl, and 1.4-1.6 mL of 0.75% hyperbaric bupivacaine hydrochloride. Within 30 minutes after birth, a bilateral transversus abdominus plane block was performed using 266 mg of 1.3% liposomal bupivacaine and 52 mg of 0.25% bupivacaine hydrochloride.
Using the block as time point zero, maternal blood and breast milk samples were collected at hour 2, 6, 12, 24, 48, 72, and 96. Sparse sampling was employed, such that participants were randomly assigned in a 1:1 ratio to provide paired blood and milk samples at hour 2, 12, and 48; or hour 6, 24, 72, and 96. Bupivacaine was quantified in samples by liquid chromatography–tandem mass spectrometry.
Using these data, the investigators determined bupivacaine concentrations in plasma and milk, milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage. In addition, adverse events in both mothers and neonates were recorded for 2 weeks post partum.
Mean bupivacaine concentrations peaked in breast milk at 6 hours, at 58 ng/mL. This peak was followed by a steady reduction to an “almost undetectable” level of 5.2 ng/mL at 96 hours. Maternal plasma levels peaked first at hour 6 (155.9 ng/mL), then again at hour 48 (225.8 ng/mL), followed by a steady decline until hour 96, when the level reached 80.6 ng/mL.
Relative mean concentrations of milk to plasma were 44%, 36%, 28%, and 18% at hour 2, 6, 12, and 24, respectively. AUC ratios were used to represent exposure across various time intervals. For instance, the AUC ratio for milk/plasma from hour 0 to hour 2 was 0.45. The AUC findings declined steadily until the final ratio, which spanned hour 0 to hour 96, at 0.15.
These AUC ratios allowed for calculation of neonatal dosage and relative neonatal dosage using an average daily milk intake of 150 mL/kg per day. For the longest range, spanning from hour 0 to hour 96, the neonatal dosage was 15,155.4 ng/kg, which translated to a relative neonatal dosage of 0.396%.
No mothers or neonates experienced adverse events.
“Bupivacaine was transferred into mother’s milk such that an exclusively breastfeeding neonate would ingest less than 1% (relative neonatal dosage) of the maternal dose,” the investigators wrote, noting that this falls safely below the acceptable threshold of 10%.
“Because bupivacaine is metabolized primarily in the liver, a neonate’s absorption will likely be even lower [than modeled] given the first-pass effect,” they added.
Based on these findings, Dr. Mustafa and colleagues concluded that “the level of bupivacaine ingested by the sucking neonate is acceptable and compatible with breastfeeding.”
Michael G. Ross MD, MPH, Distinguished Professor of Obstetrics and Gynecology and Public Health at Geffen School of Medicine at the University of California, Los Angeles, commented that, this study adds to the literature of drug excretion into breast milk. “For the vast majority of drugs with passive transfer from maternal plasma to breast milk, the effective dosages of exclusive breastfeeding neonates are approximately 5% of the maternal (oral) dose. In the present study, the authors demonstrated a relative neonatal dosage of less than 1%. This low value results from consequences of minimal maternal plasma absorption (in the present case from transversus abdominis injection), maternal volume of distribution, transfer into breast milk, and the volume of milk ingestion. These results should provide reassurance for the safety of breastfeeding term infants under the conditions of the study.
“There are a number of study concerns, including the inability to differentiate absorption of the spinal bupivacaine from the liposomal bupivacaine, the lack of paired maternal plasma and breast milk sample, and the lack of detail as to how much milk was expressed for each sample. Importantly, breast milk composition varies from foremilk to hindmilk. Thus, a single sample may not accurately reflect the composition ingested by the infant. The suggestion of two peaks in maternal plasma concentration was not demonstrated statistically and may be an artifact of the timing of spinal and liposomal injections, or the fact that different patients were studied at each time period.
“Most importantly, despite the demonstrated safety, the authors acknowledge conflicting results of clinical benefits of liposomal bupivacaine injection. As such, I recommend that postcesarean transversus abdominis blocks be performed only under institutional review board-approved study protocols,” said Dr. Ross, codirector of the Institute for Women’ and Children’s Health at the Lundquist Institute, Torrance, Calif.*
The study was funded by the Thrasher Research Fund. The investigators reported no conflicts of interest. Dr. Ross had no relevant financial disclosures.
SOURCE: Mustafa et al. Obstet Gynecol. 2020 Jun 6. doi: 10.1097/AOG.0000000000003886.
*This article was updated 6/16/2020.
based on a prospective cohort study.
Over the course of 4 days, relative neonatal dosages of bupivacaine were less than 1%, remaining below the 10% threshold of concern, reported Hiba J. Mustafa, MD, of the University of Minnesota, Minneapolis, and colleagues.
Liposomal bupivacaine can achieve up to 4 days of postcesarean pain control, which is significantly longer than the 8 hours provided by standard bupivacaine, the investigators wrote in Obstetrics & Gynecology. But usage of the liposomal formulation has not been widespread, they noted, partly because of a lack of clinical studies evaluating breast milk transfer and neonatal safety.
To address this knowledge gap, Dr. Mustafa and colleagues enrolled 30 healthy pregnant women scheduled to undergo cesarean birth at full term. All patients were aged 18-40 years, with an American Society of Anesthesiologists physical status of I or II. Exclusion criteria included a number of maternal and neonatal health concerns, such as sensitivity to local anesthetics, metabolic disorders, fetal anomaly, fetal growth restriction, and others.
The day of surgery, before the procedure, maternal blood samples were collected and used for baseline measurements.
Each woman received a spinal anesthetic including 150 mcg of morphine, 15 mcg of intrathecal fentanyl, and 1.4-1.6 mL of 0.75% hyperbaric bupivacaine hydrochloride. Within 30 minutes after birth, a bilateral transversus abdominus plane block was performed using 266 mg of 1.3% liposomal bupivacaine and 52 mg of 0.25% bupivacaine hydrochloride.
Using the block as time point zero, maternal blood and breast milk samples were collected at hour 2, 6, 12, 24, 48, 72, and 96. Sparse sampling was employed, such that participants were randomly assigned in a 1:1 ratio to provide paired blood and milk samples at hour 2, 12, and 48; or hour 6, 24, 72, and 96. Bupivacaine was quantified in samples by liquid chromatography–tandem mass spectrometry.
Using these data, the investigators determined bupivacaine concentrations in plasma and milk, milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage. In addition, adverse events in both mothers and neonates were recorded for 2 weeks post partum.
Mean bupivacaine concentrations peaked in breast milk at 6 hours, at 58 ng/mL. This peak was followed by a steady reduction to an “almost undetectable” level of 5.2 ng/mL at 96 hours. Maternal plasma levels peaked first at hour 6 (155.9 ng/mL), then again at hour 48 (225.8 ng/mL), followed by a steady decline until hour 96, when the level reached 80.6 ng/mL.
Relative mean concentrations of milk to plasma were 44%, 36%, 28%, and 18% at hour 2, 6, 12, and 24, respectively. AUC ratios were used to represent exposure across various time intervals. For instance, the AUC ratio for milk/plasma from hour 0 to hour 2 was 0.45. The AUC findings declined steadily until the final ratio, which spanned hour 0 to hour 96, at 0.15.
These AUC ratios allowed for calculation of neonatal dosage and relative neonatal dosage using an average daily milk intake of 150 mL/kg per day. For the longest range, spanning from hour 0 to hour 96, the neonatal dosage was 15,155.4 ng/kg, which translated to a relative neonatal dosage of 0.396%.
No mothers or neonates experienced adverse events.
“Bupivacaine was transferred into mother’s milk such that an exclusively breastfeeding neonate would ingest less than 1% (relative neonatal dosage) of the maternal dose,” the investigators wrote, noting that this falls safely below the acceptable threshold of 10%.
“Because bupivacaine is metabolized primarily in the liver, a neonate’s absorption will likely be even lower [than modeled] given the first-pass effect,” they added.
Based on these findings, Dr. Mustafa and colleagues concluded that “the level of bupivacaine ingested by the sucking neonate is acceptable and compatible with breastfeeding.”
Michael G. Ross MD, MPH, Distinguished Professor of Obstetrics and Gynecology and Public Health at Geffen School of Medicine at the University of California, Los Angeles, commented that, this study adds to the literature of drug excretion into breast milk. “For the vast majority of drugs with passive transfer from maternal plasma to breast milk, the effective dosages of exclusive breastfeeding neonates are approximately 5% of the maternal (oral) dose. In the present study, the authors demonstrated a relative neonatal dosage of less than 1%. This low value results from consequences of minimal maternal plasma absorption (in the present case from transversus abdominis injection), maternal volume of distribution, transfer into breast milk, and the volume of milk ingestion. These results should provide reassurance for the safety of breastfeeding term infants under the conditions of the study.
“There are a number of study concerns, including the inability to differentiate absorption of the spinal bupivacaine from the liposomal bupivacaine, the lack of paired maternal plasma and breast milk sample, and the lack of detail as to how much milk was expressed for each sample. Importantly, breast milk composition varies from foremilk to hindmilk. Thus, a single sample may not accurately reflect the composition ingested by the infant. The suggestion of two peaks in maternal plasma concentration was not demonstrated statistically and may be an artifact of the timing of spinal and liposomal injections, or the fact that different patients were studied at each time period.
“Most importantly, despite the demonstrated safety, the authors acknowledge conflicting results of clinical benefits of liposomal bupivacaine injection. As such, I recommend that postcesarean transversus abdominis blocks be performed only under institutional review board-approved study protocols,” said Dr. Ross, codirector of the Institute for Women’ and Children’s Health at the Lundquist Institute, Torrance, Calif.*
The study was funded by the Thrasher Research Fund. The investigators reported no conflicts of interest. Dr. Ross had no relevant financial disclosures.
SOURCE: Mustafa et al. Obstet Gynecol. 2020 Jun 6. doi: 10.1097/AOG.0000000000003886.
*This article was updated 6/16/2020.
based on a prospective cohort study.
Over the course of 4 days, relative neonatal dosages of bupivacaine were less than 1%, remaining below the 10% threshold of concern, reported Hiba J. Mustafa, MD, of the University of Minnesota, Minneapolis, and colleagues.
Liposomal bupivacaine can achieve up to 4 days of postcesarean pain control, which is significantly longer than the 8 hours provided by standard bupivacaine, the investigators wrote in Obstetrics & Gynecology. But usage of the liposomal formulation has not been widespread, they noted, partly because of a lack of clinical studies evaluating breast milk transfer and neonatal safety.
To address this knowledge gap, Dr. Mustafa and colleagues enrolled 30 healthy pregnant women scheduled to undergo cesarean birth at full term. All patients were aged 18-40 years, with an American Society of Anesthesiologists physical status of I or II. Exclusion criteria included a number of maternal and neonatal health concerns, such as sensitivity to local anesthetics, metabolic disorders, fetal anomaly, fetal growth restriction, and others.
The day of surgery, before the procedure, maternal blood samples were collected and used for baseline measurements.
Each woman received a spinal anesthetic including 150 mcg of morphine, 15 mcg of intrathecal fentanyl, and 1.4-1.6 mL of 0.75% hyperbaric bupivacaine hydrochloride. Within 30 minutes after birth, a bilateral transversus abdominus plane block was performed using 266 mg of 1.3% liposomal bupivacaine and 52 mg of 0.25% bupivacaine hydrochloride.
Using the block as time point zero, maternal blood and breast milk samples were collected at hour 2, 6, 12, 24, 48, 72, and 96. Sparse sampling was employed, such that participants were randomly assigned in a 1:1 ratio to provide paired blood and milk samples at hour 2, 12, and 48; or hour 6, 24, 72, and 96. Bupivacaine was quantified in samples by liquid chromatography–tandem mass spectrometry.
Using these data, the investigators determined bupivacaine concentrations in plasma and milk, milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage. In addition, adverse events in both mothers and neonates were recorded for 2 weeks post partum.
Mean bupivacaine concentrations peaked in breast milk at 6 hours, at 58 ng/mL. This peak was followed by a steady reduction to an “almost undetectable” level of 5.2 ng/mL at 96 hours. Maternal plasma levels peaked first at hour 6 (155.9 ng/mL), then again at hour 48 (225.8 ng/mL), followed by a steady decline until hour 96, when the level reached 80.6 ng/mL.
Relative mean concentrations of milk to plasma were 44%, 36%, 28%, and 18% at hour 2, 6, 12, and 24, respectively. AUC ratios were used to represent exposure across various time intervals. For instance, the AUC ratio for milk/plasma from hour 0 to hour 2 was 0.45. The AUC findings declined steadily until the final ratio, which spanned hour 0 to hour 96, at 0.15.
These AUC ratios allowed for calculation of neonatal dosage and relative neonatal dosage using an average daily milk intake of 150 mL/kg per day. For the longest range, spanning from hour 0 to hour 96, the neonatal dosage was 15,155.4 ng/kg, which translated to a relative neonatal dosage of 0.396%.
No mothers or neonates experienced adverse events.
“Bupivacaine was transferred into mother’s milk such that an exclusively breastfeeding neonate would ingest less than 1% (relative neonatal dosage) of the maternal dose,” the investigators wrote, noting that this falls safely below the acceptable threshold of 10%.
“Because bupivacaine is metabolized primarily in the liver, a neonate’s absorption will likely be even lower [than modeled] given the first-pass effect,” they added.
Based on these findings, Dr. Mustafa and colleagues concluded that “the level of bupivacaine ingested by the sucking neonate is acceptable and compatible with breastfeeding.”
Michael G. Ross MD, MPH, Distinguished Professor of Obstetrics and Gynecology and Public Health at Geffen School of Medicine at the University of California, Los Angeles, commented that, this study adds to the literature of drug excretion into breast milk. “For the vast majority of drugs with passive transfer from maternal plasma to breast milk, the effective dosages of exclusive breastfeeding neonates are approximately 5% of the maternal (oral) dose. In the present study, the authors demonstrated a relative neonatal dosage of less than 1%. This low value results from consequences of minimal maternal plasma absorption (in the present case from transversus abdominis injection), maternal volume of distribution, transfer into breast milk, and the volume of milk ingestion. These results should provide reassurance for the safety of breastfeeding term infants under the conditions of the study.
“There are a number of study concerns, including the inability to differentiate absorption of the spinal bupivacaine from the liposomal bupivacaine, the lack of paired maternal plasma and breast milk sample, and the lack of detail as to how much milk was expressed for each sample. Importantly, breast milk composition varies from foremilk to hindmilk. Thus, a single sample may not accurately reflect the composition ingested by the infant. The suggestion of two peaks in maternal plasma concentration was not demonstrated statistically and may be an artifact of the timing of spinal and liposomal injections, or the fact that different patients were studied at each time period.
“Most importantly, despite the demonstrated safety, the authors acknowledge conflicting results of clinical benefits of liposomal bupivacaine injection. As such, I recommend that postcesarean transversus abdominis blocks be performed only under institutional review board-approved study protocols,” said Dr. Ross, codirector of the Institute for Women’ and Children’s Health at the Lundquist Institute, Torrance, Calif.*
The study was funded by the Thrasher Research Fund. The investigators reported no conflicts of interest. Dr. Ross had no relevant financial disclosures.
SOURCE: Mustafa et al. Obstet Gynecol. 2020 Jun 6. doi: 10.1097/AOG.0000000000003886.
*This article was updated 6/16/2020.
FROM OBSTETRICS & GYNECOLOGY
Food deserts linked to greater pregnancy morbidity
according to a retrospective observational study published in Obstetrics & Gynecology.
Previous research has linked so-called “food deserts” to higher systolic blood pressure and an increased risk of cardiovascular events in people with coronary artery disease, the authors note.
“Research on populations in the United States confirm that increased access to supermarkets is associated with lower prevalence of overweight and obesity, and improved fruit and vegetable consumption,” said Matthew J. Tipton, MD, of Loyola University Medical Center in Chicago, and colleagues.
“With our study showing an association between living in a food desert and increased pregnancy morbidity, it is our hope that with future work, an unhealthy food environment could prove to be a modifiable factor that does contribute to disparities in pregnancy morbidity,” the authors said. “Perhaps then, one could question whether greater access to healthier foods could reduce unexplained pregnancy morbidity for this population of patients,” paving the way toward developing interventions that can then improve vulnerable women’s health.
The researchers reviewed the electronic medical records of all the pregnant patients who delivered at Loyola University Medical Center in 2014. To determine who lived in a food desert, the authors relied on data about grocery food availability within Census tracts from the U.S. Department of Agriculture Food Access Research Atlas.
Dr. Tipton and associates defined living in a food desert as living in a low-income Census tract “where at least 33% of the population is more than half a mile from the nearest large grocery store for an urban area or more than 10 miles for a rural area.” Low-income Census tracts are those where “at least 20% of the population has a median family income at or below 80% of the metropolitan area or state median income.”
The authors compared women’s residence within a food desert (or not) with six different pregnancy morbidities: preeclampsia, gestational hypertension, gestational diabetes, prelabor rupture of membranes, preterm labor, and intrauterine growth restriction.
Among 1,001 deliveries, about 1 in 5 women (20%) lived in a food desert. These women tended to be slightly younger than those not living in a food desert (28 vs. 30 years old), and a higher proportion of women in food deserts were black (44%) rather than white (32%). They also had a lower average income ($44,694) than those not living in food deserts ($67,005).
After adjustment for age, race, and medical insurance type (private, Medicaid, other), the researchers found that women who lived in a food desert had 1.6 times greater odds of pregnancy comorbidity than if they did not (odds ratio, 1.64; P = .004). Nearly half the women living in food deserts had any type of comorbidity (47%), compared with just over a third of women who did not (36%).
Among the six comorbidities studied, preterm rupture of membranes was significantly different before adjustment between those who lived in food deserts (16%) and those who did not (10%) (P = .015). An association with preeclampsia had borderline significance before adjustment: 13% of women in food deserts had preeclampsia, compared with 9% of women not (P = .049). After adjustment for age, race, and medical insurance, however, neither of these associations retained statistically significant differences.
The study was limited by leaving out consideration of other factors besides local food access that might influence pregnancy health, including “quality of patient-doctor communication, implicit bias, structural racism, and stress owing to concern for neighborhood safety,” Dr. Tipton and associates said.
“An additional, albeit less obvious factor that may be unique to patients suffering disproportionately from obstetric morbidity is exposure to toxic elements,” the researchers add. “It has been shown in a previous study that low-income, predominately black communities of pregnant women may suffer disproportionately from lead or arsenic exposure.”
The study did not note external funding, and the authors reported no relevant financial disclosures.
SOURCE: Tipton MJ et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003868.
according to a retrospective observational study published in Obstetrics & Gynecology.
Previous research has linked so-called “food deserts” to higher systolic blood pressure and an increased risk of cardiovascular events in people with coronary artery disease, the authors note.
“Research on populations in the United States confirm that increased access to supermarkets is associated with lower prevalence of overweight and obesity, and improved fruit and vegetable consumption,” said Matthew J. Tipton, MD, of Loyola University Medical Center in Chicago, and colleagues.
“With our study showing an association between living in a food desert and increased pregnancy morbidity, it is our hope that with future work, an unhealthy food environment could prove to be a modifiable factor that does contribute to disparities in pregnancy morbidity,” the authors said. “Perhaps then, one could question whether greater access to healthier foods could reduce unexplained pregnancy morbidity for this population of patients,” paving the way toward developing interventions that can then improve vulnerable women’s health.
The researchers reviewed the electronic medical records of all the pregnant patients who delivered at Loyola University Medical Center in 2014. To determine who lived in a food desert, the authors relied on data about grocery food availability within Census tracts from the U.S. Department of Agriculture Food Access Research Atlas.
Dr. Tipton and associates defined living in a food desert as living in a low-income Census tract “where at least 33% of the population is more than half a mile from the nearest large grocery store for an urban area or more than 10 miles for a rural area.” Low-income Census tracts are those where “at least 20% of the population has a median family income at or below 80% of the metropolitan area or state median income.”
The authors compared women’s residence within a food desert (or not) with six different pregnancy morbidities: preeclampsia, gestational hypertension, gestational diabetes, prelabor rupture of membranes, preterm labor, and intrauterine growth restriction.
Among 1,001 deliveries, about 1 in 5 women (20%) lived in a food desert. These women tended to be slightly younger than those not living in a food desert (28 vs. 30 years old), and a higher proportion of women in food deserts were black (44%) rather than white (32%). They also had a lower average income ($44,694) than those not living in food deserts ($67,005).
After adjustment for age, race, and medical insurance type (private, Medicaid, other), the researchers found that women who lived in a food desert had 1.6 times greater odds of pregnancy comorbidity than if they did not (odds ratio, 1.64; P = .004). Nearly half the women living in food deserts had any type of comorbidity (47%), compared with just over a third of women who did not (36%).
Among the six comorbidities studied, preterm rupture of membranes was significantly different before adjustment between those who lived in food deserts (16%) and those who did not (10%) (P = .015). An association with preeclampsia had borderline significance before adjustment: 13% of women in food deserts had preeclampsia, compared with 9% of women not (P = .049). After adjustment for age, race, and medical insurance, however, neither of these associations retained statistically significant differences.
The study was limited by leaving out consideration of other factors besides local food access that might influence pregnancy health, including “quality of patient-doctor communication, implicit bias, structural racism, and stress owing to concern for neighborhood safety,” Dr. Tipton and associates said.
“An additional, albeit less obvious factor that may be unique to patients suffering disproportionately from obstetric morbidity is exposure to toxic elements,” the researchers add. “It has been shown in a previous study that low-income, predominately black communities of pregnant women may suffer disproportionately from lead or arsenic exposure.”
The study did not note external funding, and the authors reported no relevant financial disclosures.
SOURCE: Tipton MJ et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003868.
according to a retrospective observational study published in Obstetrics & Gynecology.
Previous research has linked so-called “food deserts” to higher systolic blood pressure and an increased risk of cardiovascular events in people with coronary artery disease, the authors note.
“Research on populations in the United States confirm that increased access to supermarkets is associated with lower prevalence of overweight and obesity, and improved fruit and vegetable consumption,” said Matthew J. Tipton, MD, of Loyola University Medical Center in Chicago, and colleagues.
“With our study showing an association between living in a food desert and increased pregnancy morbidity, it is our hope that with future work, an unhealthy food environment could prove to be a modifiable factor that does contribute to disparities in pregnancy morbidity,” the authors said. “Perhaps then, one could question whether greater access to healthier foods could reduce unexplained pregnancy morbidity for this population of patients,” paving the way toward developing interventions that can then improve vulnerable women’s health.
The researchers reviewed the electronic medical records of all the pregnant patients who delivered at Loyola University Medical Center in 2014. To determine who lived in a food desert, the authors relied on data about grocery food availability within Census tracts from the U.S. Department of Agriculture Food Access Research Atlas.
Dr. Tipton and associates defined living in a food desert as living in a low-income Census tract “where at least 33% of the population is more than half a mile from the nearest large grocery store for an urban area or more than 10 miles for a rural area.” Low-income Census tracts are those where “at least 20% of the population has a median family income at or below 80% of the metropolitan area or state median income.”
The authors compared women’s residence within a food desert (or not) with six different pregnancy morbidities: preeclampsia, gestational hypertension, gestational diabetes, prelabor rupture of membranes, preterm labor, and intrauterine growth restriction.
Among 1,001 deliveries, about 1 in 5 women (20%) lived in a food desert. These women tended to be slightly younger than those not living in a food desert (28 vs. 30 years old), and a higher proportion of women in food deserts were black (44%) rather than white (32%). They also had a lower average income ($44,694) than those not living in food deserts ($67,005).
After adjustment for age, race, and medical insurance type (private, Medicaid, other), the researchers found that women who lived in a food desert had 1.6 times greater odds of pregnancy comorbidity than if they did not (odds ratio, 1.64; P = .004). Nearly half the women living in food deserts had any type of comorbidity (47%), compared with just over a third of women who did not (36%).
Among the six comorbidities studied, preterm rupture of membranes was significantly different before adjustment between those who lived in food deserts (16%) and those who did not (10%) (P = .015). An association with preeclampsia had borderline significance before adjustment: 13% of women in food deserts had preeclampsia, compared with 9% of women not (P = .049). After adjustment for age, race, and medical insurance, however, neither of these associations retained statistically significant differences.
The study was limited by leaving out consideration of other factors besides local food access that might influence pregnancy health, including “quality of patient-doctor communication, implicit bias, structural racism, and stress owing to concern for neighborhood safety,” Dr. Tipton and associates said.
“An additional, albeit less obvious factor that may be unique to patients suffering disproportionately from obstetric morbidity is exposure to toxic elements,” the researchers add. “It has been shown in a previous study that low-income, predominately black communities of pregnant women may suffer disproportionately from lead or arsenic exposure.”
The study did not note external funding, and the authors reported no relevant financial disclosures.
SOURCE: Tipton MJ et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000003868.
FROM OBSTETRICS & GYNECOLOGY
Does cultural tailoring of sexual health programs lead to safer behavior?
including abstinence, condom use, and number of sex partners, a meta-analysis of 12 studies suggests.
Furthermore, cultural tailoring may contribute to a program’s success, the data indicate.
“It is important that culturally tailored sexual health programs be available to Hispanic communities across the United States,” the study authors stated in Pediatrics.
To examine the effects of sexual health interventions on behavioral outcomes among Hispanic adolescents and factors that may influence the success of an intervention, Reina Evans, a doctoral student in the department of psychology at North Carolina State University in Raleigh, and colleagues systemically reviewed published studies that included Hispanic adolescents in the United States. Included studies evaluated a sexual health intervention using an experimental or quasiexperimental design and assessed a behavioral outcome.
The researchers synthesized effect sizes from 12 studies that included 4,673 Hispanic adolescents. “As the indicator of effect size, the standardized mean difference, Cohen’s d, was used,” they said. Effect size was interpreted as small at 0.20, medium at 0.50, and large at 0.80.
Sexual health interventions improved abstinence (d = 0.15), condom use (d = 0.44), number of sex partners (d = –0.19), and sexual health knowledge (d = 0.40), compared with control conditions.
Eight of the 12 interventions incorporated Hispanic-specific practices and values such as familialism into the intervention materials. Culturally tailored interventions produced greater change in condom use, compared with interventions that were not culturally tailored. One intervention with a large effect on condom use was developed by researchers in collaboration with community members, the authors said. Another program with a large effect on condom use was designed for Hispanic families.
Ten of the 12 studies included males and females, and two included only females. Intervention dose ranged from less than 10 hours of program content to more than 20 hours of content.
Definitions of abstinence and time frames for reporting recent condom use varied across studies, the researchers noted. Data about patient characteristics, such as the percentage of participants born in the United States, and pregnancy outcomes were limited. These domains could be areas of future research.
“Latinx adolescents are disproportionately burdened with unplanned pregnancy and STIs [sexually transmitted infections]. In this meta-analysis, it is shown that sexual health interventions can play a role in combating these health disparities,” Ms. Evans and associates said.
Among Hispanic adolescents, persistent disparities in sexual and reproductive health “remain a national public health priority,” and “strengthening the effects of future ... interventions for Hispanic adolescents is needed,” said Vincent Guilamo-Ramos, PhD, MPH, and colleagues in an accompanying editorial. Dr. Guilamo-Ramos is a professor of social work and director and founder of the Center for Latino Adolescent and Family Health at New York University.
“Evans et al. highlighted that reporting on the foreign-born participant proportions was incomplete across studies, thereby excluding this clinical heterogeneity domain from formal moderation analyses,” said Dr. Guilamo-Ramos and colleagues. People who develop Hispanic sexual and reproductive health interventions may consider whether this domain or other domains moderate intervention effectiveness.
Although sensitivity analyses focused on several potential sources of bias, “other domains of potential methodologic heterogeneity, such as refusal bias, differential attrition, or information bias, remained unaccounted for,” they said.
“Attention to clinical, methodologic, and statistical heterogeneity across studies can yield insights into factors associated with bolstering intervention effectiveness. Cultural tailoring to increase the effectiveness of condom interventions for Hispanic adolescents is one such intervention effect modifier,” Dr. Guilamo-Ramos and associates concluded.
The study authors had no relevant financial disclosures. The research was supported by the Doug Kirby Adolescent Sexual Health Research Grant from the Rural Center for AIDS and Sexually Transmitted Disease Prevention, Indiana University School of Public Health–Bloomington, and the Center for Family and Community Engagement, North Carolina State University. The editorialists are supported by the William T. Grant Foundation and the National Institutes of Health. In addition, Dr. Guilamo-Ramos has received grants and personal fees from ViiV Healthcare outside the submitted work and serves as a member of the U.S. Presidential Advisory Council on HIV/AIDS and as the vice chair of the board of directors of the Latino Commission on AIDS. His coauthors had no relevant financial disclosures.
SOURCES: Evans R et al. Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2019-3572; Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2020-1406.
including abstinence, condom use, and number of sex partners, a meta-analysis of 12 studies suggests.
Furthermore, cultural tailoring may contribute to a program’s success, the data indicate.
“It is important that culturally tailored sexual health programs be available to Hispanic communities across the United States,” the study authors stated in Pediatrics.
To examine the effects of sexual health interventions on behavioral outcomes among Hispanic adolescents and factors that may influence the success of an intervention, Reina Evans, a doctoral student in the department of psychology at North Carolina State University in Raleigh, and colleagues systemically reviewed published studies that included Hispanic adolescents in the United States. Included studies evaluated a sexual health intervention using an experimental or quasiexperimental design and assessed a behavioral outcome.
The researchers synthesized effect sizes from 12 studies that included 4,673 Hispanic adolescents. “As the indicator of effect size, the standardized mean difference, Cohen’s d, was used,” they said. Effect size was interpreted as small at 0.20, medium at 0.50, and large at 0.80.
Sexual health interventions improved abstinence (d = 0.15), condom use (d = 0.44), number of sex partners (d = –0.19), and sexual health knowledge (d = 0.40), compared with control conditions.
Eight of the 12 interventions incorporated Hispanic-specific practices and values such as familialism into the intervention materials. Culturally tailored interventions produced greater change in condom use, compared with interventions that were not culturally tailored. One intervention with a large effect on condom use was developed by researchers in collaboration with community members, the authors said. Another program with a large effect on condom use was designed for Hispanic families.
Ten of the 12 studies included males and females, and two included only females. Intervention dose ranged from less than 10 hours of program content to more than 20 hours of content.
Definitions of abstinence and time frames for reporting recent condom use varied across studies, the researchers noted. Data about patient characteristics, such as the percentage of participants born in the United States, and pregnancy outcomes were limited. These domains could be areas of future research.
“Latinx adolescents are disproportionately burdened with unplanned pregnancy and STIs [sexually transmitted infections]. In this meta-analysis, it is shown that sexual health interventions can play a role in combating these health disparities,” Ms. Evans and associates said.
Among Hispanic adolescents, persistent disparities in sexual and reproductive health “remain a national public health priority,” and “strengthening the effects of future ... interventions for Hispanic adolescents is needed,” said Vincent Guilamo-Ramos, PhD, MPH, and colleagues in an accompanying editorial. Dr. Guilamo-Ramos is a professor of social work and director and founder of the Center for Latino Adolescent and Family Health at New York University.
“Evans et al. highlighted that reporting on the foreign-born participant proportions was incomplete across studies, thereby excluding this clinical heterogeneity domain from formal moderation analyses,” said Dr. Guilamo-Ramos and colleagues. People who develop Hispanic sexual and reproductive health interventions may consider whether this domain or other domains moderate intervention effectiveness.
Although sensitivity analyses focused on several potential sources of bias, “other domains of potential methodologic heterogeneity, such as refusal bias, differential attrition, or information bias, remained unaccounted for,” they said.
“Attention to clinical, methodologic, and statistical heterogeneity across studies can yield insights into factors associated with bolstering intervention effectiveness. Cultural tailoring to increase the effectiveness of condom interventions for Hispanic adolescents is one such intervention effect modifier,” Dr. Guilamo-Ramos and associates concluded.
The study authors had no relevant financial disclosures. The research was supported by the Doug Kirby Adolescent Sexual Health Research Grant from the Rural Center for AIDS and Sexually Transmitted Disease Prevention, Indiana University School of Public Health–Bloomington, and the Center for Family and Community Engagement, North Carolina State University. The editorialists are supported by the William T. Grant Foundation and the National Institutes of Health. In addition, Dr. Guilamo-Ramos has received grants and personal fees from ViiV Healthcare outside the submitted work and serves as a member of the U.S. Presidential Advisory Council on HIV/AIDS and as the vice chair of the board of directors of the Latino Commission on AIDS. His coauthors had no relevant financial disclosures.
SOURCES: Evans R et al. Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2019-3572; Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2020-1406.
including abstinence, condom use, and number of sex partners, a meta-analysis of 12 studies suggests.
Furthermore, cultural tailoring may contribute to a program’s success, the data indicate.
“It is important that culturally tailored sexual health programs be available to Hispanic communities across the United States,” the study authors stated in Pediatrics.
To examine the effects of sexual health interventions on behavioral outcomes among Hispanic adolescents and factors that may influence the success of an intervention, Reina Evans, a doctoral student in the department of psychology at North Carolina State University in Raleigh, and colleagues systemically reviewed published studies that included Hispanic adolescents in the United States. Included studies evaluated a sexual health intervention using an experimental or quasiexperimental design and assessed a behavioral outcome.
The researchers synthesized effect sizes from 12 studies that included 4,673 Hispanic adolescents. “As the indicator of effect size, the standardized mean difference, Cohen’s d, was used,” they said. Effect size was interpreted as small at 0.20, medium at 0.50, and large at 0.80.
Sexual health interventions improved abstinence (d = 0.15), condom use (d = 0.44), number of sex partners (d = –0.19), and sexual health knowledge (d = 0.40), compared with control conditions.
Eight of the 12 interventions incorporated Hispanic-specific practices and values such as familialism into the intervention materials. Culturally tailored interventions produced greater change in condom use, compared with interventions that were not culturally tailored. One intervention with a large effect on condom use was developed by researchers in collaboration with community members, the authors said. Another program with a large effect on condom use was designed for Hispanic families.
Ten of the 12 studies included males and females, and two included only females. Intervention dose ranged from less than 10 hours of program content to more than 20 hours of content.
Definitions of abstinence and time frames for reporting recent condom use varied across studies, the researchers noted. Data about patient characteristics, such as the percentage of participants born in the United States, and pregnancy outcomes were limited. These domains could be areas of future research.
“Latinx adolescents are disproportionately burdened with unplanned pregnancy and STIs [sexually transmitted infections]. In this meta-analysis, it is shown that sexual health interventions can play a role in combating these health disparities,” Ms. Evans and associates said.
Among Hispanic adolescents, persistent disparities in sexual and reproductive health “remain a national public health priority,” and “strengthening the effects of future ... interventions for Hispanic adolescents is needed,” said Vincent Guilamo-Ramos, PhD, MPH, and colleagues in an accompanying editorial. Dr. Guilamo-Ramos is a professor of social work and director and founder of the Center for Latino Adolescent and Family Health at New York University.
“Evans et al. highlighted that reporting on the foreign-born participant proportions was incomplete across studies, thereby excluding this clinical heterogeneity domain from formal moderation analyses,” said Dr. Guilamo-Ramos and colleagues. People who develop Hispanic sexual and reproductive health interventions may consider whether this domain or other domains moderate intervention effectiveness.
Although sensitivity analyses focused on several potential sources of bias, “other domains of potential methodologic heterogeneity, such as refusal bias, differential attrition, or information bias, remained unaccounted for,” they said.
“Attention to clinical, methodologic, and statistical heterogeneity across studies can yield insights into factors associated with bolstering intervention effectiveness. Cultural tailoring to increase the effectiveness of condom interventions for Hispanic adolescents is one such intervention effect modifier,” Dr. Guilamo-Ramos and associates concluded.
The study authors had no relevant financial disclosures. The research was supported by the Doug Kirby Adolescent Sexual Health Research Grant from the Rural Center for AIDS and Sexually Transmitted Disease Prevention, Indiana University School of Public Health–Bloomington, and the Center for Family and Community Engagement, North Carolina State University. The editorialists are supported by the William T. Grant Foundation and the National Institutes of Health. In addition, Dr. Guilamo-Ramos has received grants and personal fees from ViiV Healthcare outside the submitted work and serves as a member of the U.S. Presidential Advisory Council on HIV/AIDS and as the vice chair of the board of directors of the Latino Commission on AIDS. His coauthors had no relevant financial disclosures.
SOURCES: Evans R et al. Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2019-3572; Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2020-1406.
FROM PEDIATRICS
Key clinical point: Among Hispanic adolescents, sexual health interventions have a small but significant effect on improving safe sexual behavior. Cultural tailoring may contribute to a program’s success.
Major finding: Sexual health interventions improved abstinence (d = 0.15), condom use (d = 0.44), number of sex partners (d = –0.19), and sexual health knowledge (d = 0.40), compared with control conditions.
Study details: A meta-analysis of 12 studies with 4,673 participants.
Disclosures: The study authors had no relevant financial disclosures. The research was supported by the Doug Kirby Adolescent Sexual Health Research Grant from the Rural Center for AIDS and Sexually Transmitted Disease Prevention, Indiana University School of Public Health–Bloomington, and the Center for Family and Community Engagement, North Carolina State University.
Source: Evans R et al. Pediatrics. 2020 Jun 10. doi: 10.1542/peds.2019-3572.
Large study finds no link between gluten, IBD risk
Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.
The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.®
“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”
Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.
To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.
Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.
After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”
She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”
Dr. Lopes reported having no conflicts of interest.
SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.
Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.
The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.®
“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”
Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.
To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.
Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.
After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”
She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”
Dr. Lopes reported having no conflicts of interest.
SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.
Among women without celiac disease, dietary gluten intake was not associated with the risk of developing either Crohn’s disease or ulcerative colitis, investigators reported.
The findings spanned subgroups stratified by age, body mass index, smoking status, and whether individuals primarily consumed refined or whole grains, said Emily Walsh Lopes, MD, gastroenterology clinical and research fellow at Massachusetts General Hospital in Boston. She and associates reported the combined analysis of the prospective Nurses’ Health Study and Nurses’ Health Study II in an abstract released as part of the annual Digestive Disease Week.®
“Avoidance of dietary gluten is common, and many patients attribute gastrointestinal symptoms to gluten intake,” Dr. Lopes said in an interview. “Though our findings warrant further study, the results suggest to patients and providers that eating gluten does not increase a person’s chance of getting diagnosed with inflammatory bowel disease.”
Prior studies have found that many individuals with inflammatory bowel disease avoid gluten and report subsequent improvements in gastrointestinal symptoms, even if they do not have celiac disease. However, it remains unclear whether dietary gluten is a risk factor for new-onset inflammatory bowel disease.
To address this question, Dr. Lopes and associates analyzed data collected from 165,327 women who took part in the Nurses’ Health Study (1986 to 2016) or the Nurses’ Health Study II (1991 through 2017). None of the women had a preexisting diagnosis of celiac disease or inflammatory bowel disease. Dietary gluten intake was estimated based on food frequency questionnaires completed by the women at baseline and every 4 years. The researchers also reviewed medical records to confirm self-reported cases of new-onset ulcerative colitis and Crohn’s disease.
Over 4.02 million person-years of follow-up, 277 women developed Crohn’s disease and 359 developed ulcerative colitis. Gluten intake was not associated with the risk of either type of inflammatory bowel disease, even after the researchers controlled for multiple demographic and clinical risk factors.
After submitting their abstract, Dr. Lopes and coinvestigators expanded the dataset to include a large cohort of men from the prospective Health Professionals Follow-up Study. The final pooled cohort included more than 208,000 women and men followed for more than 20 years. Through the end of follow-up, the researchers documented 337 cases of Crohn’s disease and 446 cases of ulcerative colitis. “Inclusion of the male cohort in the pooled analysis did not materially change our estimates,” Dr. Lopes told MDedge. “That is, no association was seen between gluten intake and risk of either Crohn’s disease or ulcerative colitis in the final cohort.”
She noted that the findings cannot be extrapolated to individuals who are already diagnosed with inflammatory bowel disease. “It is possible that different mechanisms exist to explain how gluten intake impacts those already diagnosed with IBD, and this topic warrants further study,” she said. Also, because the three cohort studies were observational, they are subject to bias. “While we tried to account for this in our analyses, residual bias may still exist.”
Dr. Lopes reported having no conflicts of interest.
SOURCE: Walsh Lopes E et al. DDW 2020, abstract 847.
FROM DDW 2020
High ‘forever chemicals’ in blood linked to earlier menopause
In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.
That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).
“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.
“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.
PFAS don’t break down in the body, build up with time
PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.
These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.
“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”
Environmental exposure and accelerated ovarian aging
Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.
PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.
A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).
But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).
There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.
In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).
The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.
The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).
Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.
Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.
Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.
Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.
Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.
Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.
“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.
SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.
That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).
“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.
“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.
PFAS don’t break down in the body, build up with time
PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.
These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.
“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”
Environmental exposure and accelerated ovarian aging
Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.
PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.
A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).
But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).
There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.
In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).
The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.
The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).
Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.
Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.
Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.
Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.
Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.
Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.
“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.
SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a national sample of U.S. women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.
That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1,100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study, which excluded women with premature menopause (before age 40) or early menopause (before age 45).
“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan, Ann Arbor, and colleagues concluded in their article, published online June 3 in the Journal of Clinical Endocrinology & Metabolism.
“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” senior author Sung Kyun Park, ScD, MPH, from the same institution, added in a statement.
PFAS don’t break down in the body, build up with time
PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explained.
These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.
“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Dr. Ding. “Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals.”
Environmental exposure and accelerated ovarian aging
Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors wrote.
PFAS, especially the most studied types – perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) – are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.
A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).
But in research based on National Health and Nutrition Survey Examination data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).
There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.
In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).
The current analysis examined data from 1,120 premenopausal women who were aged 45-56 years from 1999 to 2000.
The women were seen at five sites (Boston; Detroit; Los Angeles; Oakland, Calif.; and Pittsburgh) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).
Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry. The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews.
Of the 1,120 women and 5,466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis. The remaining 542 women were excluded mainly because their date of final menstruation was unknown because of hormone therapy (451) or they had a hysterectomy, or did not enter menopause during the study.
Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26%-27% greater risk of incident menopause – after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.
Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.
Compared with women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% confidence interval, 1.08-2.45), equivalent to having menopause a median of 2 years earlier.
Although production and use of some types of PFAS in the United States are declining, Dr. Ding and colleagues wrote, exposure continues, along with associated potential hazards to human reproductive health.
“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they concluded.
SWAN was supported by the National Institutes of Health, Department of Health & Human Services through the National Institute on Aging, National Institute of Nursing Research, NIH Office of Research on Women’s Health, and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Managing a woman with BRCA mutations? Shared decision-making is key
CASE
Sara T* recently moved back to the area to be closer to her family. The 34-year-old patient visited our office to discuss the benefits and potential risks of genetic counseling. She explained that her aunt had just died at age 64 of ovarian cancer. Also, her maternal cousin had been diagnosed at age 42 with breast cancer, and her maternal grandmother had died at age 45 of an unknown “female cancer.” She was scared to find out if she had high-risk genes because she felt it would change her life forever. However, if she ignored the issue, she thought she might worry too much.
We discussed the implications of a positive result, such as having to live with the knowledge and to make decisions about potential screening and risk-reducing surgery. On the other hand, not knowing could allow for the undetected growth of cancer that might otherwise be mitigated to some degree if she knew her risk status and pursued an aggressive screening program.
We worked with Ms. T to map out her next steps.
*The patient’s name has been changed to protect her identity.
Breast cancer is the most commonly diagnosed cancer in women worldwide, representing nearly one-quarter of all female cancer diagnoses in 2018.1 It is the second-leading cause of cancer death in women in developed nations and the leading cause of cancer death in women in developing nations.1 In the United States, 1 in 8 women will develop breast cancer in her lifetime.2 By comparison, the rate of ovarian cancer is much lower, with a lifetime prevalence of 1 in 70 to 80 women.3,4 Although ovarian cancer is less common than breast cancer, its associated mortality is high, and most cases are discovered at advanced stages.
The outsized threat of BRCA mutations. It is estimated that 5% to 10% of all breast cancers are hereditary, with 80% of these attributable to BRCA1 (45%) and BRCA2 (35%).5 These autosomal dominant mutations occur at the germline level, within the egg or sperm, and are therefore incorporated into the DNA of every cell and passed from one generation to the next. Families with BRCA mutations have much higher lifetime rates of cancer. The lifetime risk of breast cancer due to BRCA mutations is estimated at > 80% (BRCA1) and 45% (BRCA2).5BRCA mutations account for between
Male BRCA carriers have a lifetime breast cancer risk of 1% to 5% with BRCA1 and 5% to 10% with BRCA2,7,8 compared with about 1:1000 lifetime incidence in the unselected male population. Male carriers are also at risk for more aggressive prostate cancers.7,8
Continue to: Certain populatiosn carry undue burden of BRCA-related disease
Certain populations carry undue burden of BRCA-related disease due to specific founder mutations. While the estimated global prevalence of BRCA mutations is 0.2% to 1%, for those of Ashkenazi Jewish descent the range is 2% to 3%, representing a relative risk up to 15 times that of the general population.9 Hispanic Americans also appear to have higher rates of BRCA-related cancers.10 Ongoing genetics research continues to identify founder mutations worldwide,10 which may inform future screening guidelines.
In addition to BRCA mutations, there are other, less common mutations (TABLE 15) known to cause hereditary breast and ovarian cancer.
Identifying BRCA genes enables treatment planning. Compared with sporadic cancers, BRCA-related breast cancers
Similarly, BRCA-related ovarian cancer is more likely to be high-grade and endometrioid or serous subtype.14
Shared decision-making helps give clarity to the way forward
Shared decision-making is a process of communication whereby the clinician and the patient identify a decision to be made, review data relevant to clinical options, discuss patient perspectives and preferences regarding each option, and arrive at the decision together.17 Shared decision-making is important when treating women with BRCA mutations because there is no single correct plan. Individual values and competing medical issues may strongly guide each woman’s decisions about screening and cancer prevention treatment decisions.
Continue to: Shared decision-making in this situation...
Shared decision-making in this situation is a strategy to use the evidence of risk along with patient preferences around fertility issues to help come to a decision that is the right one for the patient. Primary care clinicians aware of the general risks and benefits of each available option can refer women at high risk for breast or ovarian cancer to a specialist multidisciplinary clinic that can provide tailored risk assessment and risk reduction counseling as needed.18-20
Genetic screening recommendations
Screening is recommended for women who have any 1 of several family risk factors (TABLE 221). A number of risk assessment tools are available for primary care clinicians to determine which patients are at high enough risk for a hereditary breast or ovarian cancer to warrant referral to a genetic counselor.22-25 If screening suggests high risk, the US Preventive Services Task Force (USPSTF) recommends (Grade B) referral for genetic counseling.21
Explain to patients who are candidates for further investigation that a genetic counselor will review their family history and recommend testing for the specific mutations that increase cancer risk. Discuss potential benefits and harms of genetic testing. A benefit of genetic testing is that aggressive screening may suggest preventive procedures to reduce the risk of future cancer. Most tests come back definitively positive or negative, but an indeterminate result may cause harm. A small minority of results may indicate a genetic variant of unknown significance. The ramifications of this variant may not be known. Some women will experience anxiety about nonspecific test results and will be afraid to share them with family members. There is also some concern about privacy issues, potential insurance bias, and coverage of any preventive strategies.26
CASE
Based on Ms. T’s family history and her desire to know more, we referred her to a genetic counselor and she decided to undergo genetic testing. She screened positive for BRCA1. Ms. T was in a serious relationship and thought she would like to have children at some point. She returned to our office after receiving the positive genetic test results, wondering about screening for breast and ovarian cancer.
Breast cancer screening and risk-reduction strategies
Screening. Because the risk of breast cancer is high in women with BRCA mutations, and because cancer in these women is more likely to be advanced at diagnosis, starting a screening program at an early age is prudent. Observational studies suggest that breastfeeding reduces the risk of breast and ovarian cancer in women with BRCA mutations, as it does for women in the general population.27 Women should return for a clinical breast exam every 6 to 12 months starting at age 25; they should start radiologic screening with magnetic resonance imaging at age 25 and mammography at age 30 (TABLE 327,28).
Continue to: Risk-reduction strategies
Risk-reduction strategies. There is weak evidence to support the use of tamoxifen or other synthetic estrogen reuptake modulators (SERMs) to reduce breast cancer risk in women with BRCA mutations. Many of these cancers do not express estrogen receptors, which may explain the lack of efficacy in certain cases. Several observational studies have shown that tamoxifen can reduce the risk of contralateral breast cancer in women with BRCA mutations who have already been diagnosed with cancer in the other breast.29-31 However, tamoxifen does not reduce a patient’s risk of ovarian cancer, and it may increase her risk of uterine cancer.
Prophylactic bilateral mastectomy is the mainstay of breast cancer prevention in this population. Data from a systematic review suggest that this surgery may prevent the incidence of breast cancer in women with BRCA mutations by 90% to 95%.32 However, this review did not demonstrate a reduction in mortality from breast cancer, likely due to poor data quality.32 The National Comprehensive Cancer Network (NCCN) recommends discussing prophylactic mastectomy with all women who have BRCA mutations.28 Further conversations are important to review the risk of tissue left behind and quality-of-life issues, including the inability to breastfeed if the woman wants more children and the cosmetic changes with reconstruction.
Ovarian cancer screening and risk-reduction strategies
Screening. No effective screening strategy has been endorsed for ovarian cancer, as most previous studies have shown screening to be ineffective.26,33 Recently, studies both in the United Kingdom and the United States have investigated a screening strategy using the risk-of-ovarian-cancer algorithm (ROCA), which calculates an individual’s risk based on serum levels of cancer antigen 125 (CA-125).34,35 These studies measured CA-125 levels every 3 to 4 months followed by transvaginal ultrasound if CA-125 increased substantially (as determined by ROCA). Absent an abnormal increase in CA-125, transvaginal ultrasound was performed annually. These screening strategies showed improved specificity over annual screening programs, and the cancers detected were more likely to be diagnosed at an early stage (stage II vs stage III) and had higher rates of zero residual disease after surgery compared with those detected 1 year after screening ended.34,35 However, survival data are not yet available. More research is needed to determine if more frequent screening approaches could improve survival in high-risk women.
NCCN and the American College of Obstetricians and Gynecologists (ACOG) do not endorse routine screening with transvaginal ultrasound and serum CA-125 for high-risk women, as the benefits are uncertain. However, they do advise that these screens may be considered as a short-term strategy for women ages 30 to 35 who defer risk-reducing surgery.26,36 The USPSTF does not make a recommendation regarding ovarian cancer screening in high-risk women.37
Risk-reduction strategies. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only recommended technique for reducing the risk of ovarian cancer in women at high risk.26,33,36 Meta-analyses have shown an 80% reduction in ovarian cancer risk16 and 68% reduction in all-cause mortality with this approach.38 The NCCN recommends RRSO for women with a known BRCA1 mutation between the ages of 35 and 40 who have completed childbearing.36 Since the onset of ovarian cancer tends to be later in women with BRCA2 mutations, it is reasonable to delay RRSO until age 40 to 45 in this population if they have taken other steps to maximize breast cancer prevention (ie, bilateral mastectomy).36
Continue to: Adverse effects of RRSO...
Adverse effects of RRSO include surgery complications (wound infection, small bowel obstruction, bladder perforation) and effects of early menopause (vasomotor symptoms, decreased sexual functioning, and increased risk of osteoporosis, cardiovascular disease, and all-cause mortality).39-41 In the absence of contraindications, ACOG recommends using hormone therapy in women undergoing RRSO until the natural age of menopause,42 particularly if their breast tissue has been removed.
Salpingectomy as an alternative. In an attempt to reduce these adverse effects of early menopause, and because a large proportion of high-grade serous tumors originate in the fallopian tube,43 interest has increased in the use of risk-reducing salpingectomy (removal of fallopian tubes) and delayed oophorectomy in women at high risk of ovarian cancer.42 Studies have shown this may be a cost-effective approach and an acceptable alternative in BRCA mutation carriers who are unwilling to undergo RRSO.44,45 A clinical trial investigating this approach in women with BRCA mutations is currently underway in the United States.46 Many centers offer salpingectomy to high-risk patients < 40 years old, understanding that ovary removal is an eventuality for these patients.
When oral contraceptive pills might be beneficial. In younger women with BRCA mutations, there may also be a role for oral contraceptive pills (OCPs) as a risk-reducing strategy. Meta-analyses have shown an approximately 50% reduction in the risk of ovarian cancer among women with BRCA mutations who use OCPs.47-49
ACOG advises that it is appropriate for women with BRCA mutations to use oral contraceptives if indicated (for pregnancy prevention or menstrual cycle regulation), and that it is reasonable to use them for cancer prevention.26 NCCN does not make a formal recommendation, although it does state OCPs may reduce the risk of ovarian cancer in women with a BRCA mutation.36 Case-control studies have produced conflicting data on the association between OCP use and breast cancer risk in BRCA mutation carriers,50-53 although 2 meta-analyses found no significant association in this population.47,48
Decision aids for women with BRCA mutations
Decision aids are visual displays of risk that help patients work through complex decisions. Most decision aids are in print or digital format and include information about the decision to be made as well as pictorial examples of possible outcomes. Pictographs are especially helpful in communicating information. Some decision aids for women with BRCA mutations can be complicated with multiple outcomes (ie, breast cancer and ovarian cancer) and multiple potential interventions (risk-reducing surgery, enhanced screening options).54
Continue to: A Cochrane review...
A Cochrane review found that decision aids increased patients’ knowledge, helped patients clarify their values, and may improve value-concordant decisions.55 Two papers describing the use of decision aids for women with BRCA mutations56,57 documented decreased decisional conflict and increased satisfaction.
CASE
Ms. T underwent the recommended mammogram and MRI screening for breast cancer, as well as testing with serum CA-125 and ultrasound examinations for ovarian cancer. Her initial mammogram and MRI revealed early stage, triple-negative right breast cancer. She chose to undergo bilateral mastectomy and reconstruction. She has now completed treatment and continues to work closely with her oncology team for appropriate breast follow-up.
One year after her initial diagnosis, at the age of 35, she returned to discuss fertility. She was recently married, and she and her husband wanted to start having children. She was concerned about a safe timeline for her to pursue pregnancy, saying she felt “like a ticking time-bomb” given her prior cancer and carrier status. She wanted to discuss the risks and benefits of pregnancy and when she should consider prophylactic oophorectomy. She had a few options. She could have a baby and then undergo an RRSO, or she could talk to her gynecologist about having a salpingectomy to reduce her risk now and use assisted reproductive technology to get pregnant. She could also freeze eggs or embryos, have an RRSO, and then use a surrogate to get pregnant. We informed her that pregnancy would not affect her risk of ovarian cancer and discussed the options for pre-implantation genetic testing to assure that her children would not carry the genetic mutation.58
We provided Ms. T and her husband with a decision aid to help them navigate the decision. They are currently evaluating the options and said they would let us know when they made a decision.
CORRESPONDENCE
Sarina Schrager, MD, MS, Northeast Family Medicine Center, 3209 Dryden Drive, Madison, WI, 53704; [email protected].
1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941-1953.
2. SEER Cancer Statistics Review, 1975-2016. Cancer of the female breast. [Table 4.1] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_04_breast.pdf. Accessed May 27, 2020.
3. SEER Cancer Statistics Review, 1975-2016. Cancer of the ovary. [Table 21.10] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_21_ovary.pdf. Accessed May 22, 2020.
4. Torre LA, Trabert B, DeSantis C, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284-296.
5. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4:665-676.
6. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807-2816.
7. Tai YC, Domchek S, Parmigiani G, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99:1811-1814.
8. Evans DG, Susnerwala I, Dawson J, et al. Risk of breast cancer in male BRCA2 carriers. J Med Genet. 2010;47:710-711.
9. CDC. Jewish women and BRCA gene mutations. www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/jewish_women_brca.htm. Accessed May 22, 2020.
10. Rebbeck TR, Friebel TM, Friedman E, et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018;39:593-620.
11. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26:3324–3330.
12. Wang YA, Jian JW, Hung CF, et al. Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer. 2018;18:315.
13. Baretta Z, Mocellin S, Goldin E, et al. Effect of BRCA germline mutations on breast cancer prognosis: a systematic review and meta-analysis. Medicine. 2016;95:e4975.
14. Lakhani SR, Manek S, Penault-Llorca F, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin Cancer Res. 2004;10:2473-2481.
15. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010;22:72-78.
16. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80-87.
17. Elwyn G, Frosch D, Thomson R, et al. Shared decision making: a model for clinical practice. J Gen Int Med. 2012;27:1361-1367.
18. Ardern-Jones A, Eeles R. Developments in clinical practice: follow up clinic for BRCA mutation carriers: a case study highlighting the “virtual clinic.” Hered Cancer Clin Pract. 2004;2:77-79.
19. Yerushalmi R, Rizel S, Zoref D, et al. A dedicated follow-up clinic for BRCA mutation carriers. Isr Med Assoc J. 2016;18:549-552.
20. Pichert G, Jacobs C, Jacobs I, et al. Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. Fam Cancer. 2010;9:313-319.
21. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019;322:652-665.
22. Evans D, Eccles D, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004;41:474-480.
23. Bellcross CA, Lemke AA, Pape LS, et al. Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population. Genet Med. 2009;11:783-789.
24. Hoskins KF, Zwaagstra A, Ranz M. Validation of a tool for identifying women at high risk for hereditary breast cancer in population based screening. Cancer. 2006;107:1769-1776.
25. Gilpin CA, Carson N, Hunter AG. A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center. Clin Genet. 2000;58:299-308.
26. Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No 182: Hereditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol. 2017;130:e110-e126.
27. Paluch-Shimon S, Cardoso F, Sessa C, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27(suppl 5):v103-v110.
28. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast and ovarian. 2019. NCCN Clinical Practice Guidelines in Oncology. www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf. Accessed May 22, 2020.
29. Phillips KA, Milne RL, Rookus MA, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091-3099.
30. Foulkes WD, Goffin J, Brunet JS, et al. Tamoxifen may be an effective adjuvant treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst. 2002;94:1504-1506.
31. Gronwald J, Tung N, Foulkes WD, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281-2284.
32. Ludwig KK, Neuner J, Butler A, et al. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. Am J Surgery. 2016;212:660-669.
33. Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.
34. Rosenthal AN, Fraser LSM, Philpott S, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom Familial Ovarian Cancer Screening Study. J Clin Oncol. 2017;35:1411-1420.
35. Skates SJ, Greene MH, Buys SS, et al. Early detection of ovarian cancer using the Risk of Ovarian Cancer Algorithm with frequent CA125 testing in women at increased familial risk—combined results from two screening trials. Clin Cancer Res. 2017;23:3628-3637.
36. Daly MB, Pilarski R, Berry M, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw. 2017;15:9-20.
37. Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:588-594.
38. Marchetti C, De Felice F, Palaia I, et al. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health. 2014;14:150.
39. Nelson HD, Pappas M, Zakher B, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2014;160:255-266.
40. Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses’ health study. Obstet Gynecol. 2013;121:709-716.
41. Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18:483-491.
42. Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian cancer prevention and screening. Obstet Gynecol. 2018;131:909-927.
43. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3-9.
44. Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol. 2013;121:14-24.
45. Holman LL, Friedman S, Daniels MS, et al. Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecol Oncol. 2014;133:283-286.
46. MD Anderson Cancer Center. Prophylactic salpingectomy with delayed oophorectomy, risk-reducing salpingo-oophorectomy, and ovarian cancer screening among BRCA mutation carriers: a proof-of-concept study. www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2013-0340.html. Accessed May 22, 2020.
47. Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer. 2010;46:2275-2284.
48. Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013;31:4188-4198.
49. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju091.
50. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev. 2006;15:1863-1870.
51. Lee E, Ma H, McKean-Cowdin R, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev. 2008;17:3170-3178.
52. Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94:1773-1779.
53. Milne RL, Knight JA, John EM, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev. 2005;14:350-356.
54. Culver JO, MacDonald DJ, Thornton AA, et al. Development and evaluation of a decision aid for BRCA carriers with breast cancer. J Genet Couns. 2011;20:294-307.
55. Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Syst Rev. 2017;4:CD001431.
56. Schwartz MD, Valdimarsdottir HB, DeMarco TA, et al. Randomized trial of a decision aid for BRCA1/BRCA2 mutation carriers: impact on measures of decision making and satisfaction. Health Psychol. 2009;28:11-19.
57. Metcalfe KA, Dennis CL, Poll A, et al. Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial. Gen Med. 2017;19:330-336.
58. Friedman LC, Kramer RM. Reproductive issues for women with BRCA mutations. J Natl Cancer Inst Monogr. 2005;34:83-86.
CASE
Sara T* recently moved back to the area to be closer to her family. The 34-year-old patient visited our office to discuss the benefits and potential risks of genetic counseling. She explained that her aunt had just died at age 64 of ovarian cancer. Also, her maternal cousin had been diagnosed at age 42 with breast cancer, and her maternal grandmother had died at age 45 of an unknown “female cancer.” She was scared to find out if she had high-risk genes because she felt it would change her life forever. However, if she ignored the issue, she thought she might worry too much.
We discussed the implications of a positive result, such as having to live with the knowledge and to make decisions about potential screening and risk-reducing surgery. On the other hand, not knowing could allow for the undetected growth of cancer that might otherwise be mitigated to some degree if she knew her risk status and pursued an aggressive screening program.
We worked with Ms. T to map out her next steps.
*The patient’s name has been changed to protect her identity.
Breast cancer is the most commonly diagnosed cancer in women worldwide, representing nearly one-quarter of all female cancer diagnoses in 2018.1 It is the second-leading cause of cancer death in women in developed nations and the leading cause of cancer death in women in developing nations.1 In the United States, 1 in 8 women will develop breast cancer in her lifetime.2 By comparison, the rate of ovarian cancer is much lower, with a lifetime prevalence of 1 in 70 to 80 women.3,4 Although ovarian cancer is less common than breast cancer, its associated mortality is high, and most cases are discovered at advanced stages.
The outsized threat of BRCA mutations. It is estimated that 5% to 10% of all breast cancers are hereditary, with 80% of these attributable to BRCA1 (45%) and BRCA2 (35%).5 These autosomal dominant mutations occur at the germline level, within the egg or sperm, and are therefore incorporated into the DNA of every cell and passed from one generation to the next. Families with BRCA mutations have much higher lifetime rates of cancer. The lifetime risk of breast cancer due to BRCA mutations is estimated at > 80% (BRCA1) and 45% (BRCA2).5BRCA mutations account for between
Male BRCA carriers have a lifetime breast cancer risk of 1% to 5% with BRCA1 and 5% to 10% with BRCA2,7,8 compared with about 1:1000 lifetime incidence in the unselected male population. Male carriers are also at risk for more aggressive prostate cancers.7,8
Continue to: Certain populatiosn carry undue burden of BRCA-related disease
Certain populations carry undue burden of BRCA-related disease due to specific founder mutations. While the estimated global prevalence of BRCA mutations is 0.2% to 1%, for those of Ashkenazi Jewish descent the range is 2% to 3%, representing a relative risk up to 15 times that of the general population.9 Hispanic Americans also appear to have higher rates of BRCA-related cancers.10 Ongoing genetics research continues to identify founder mutations worldwide,10 which may inform future screening guidelines.
In addition to BRCA mutations, there are other, less common mutations (TABLE 15) known to cause hereditary breast and ovarian cancer.
Identifying BRCA genes enables treatment planning. Compared with sporadic cancers, BRCA-related breast cancers
Similarly, BRCA-related ovarian cancer is more likely to be high-grade and endometrioid or serous subtype.14
Shared decision-making helps give clarity to the way forward
Shared decision-making is a process of communication whereby the clinician and the patient identify a decision to be made, review data relevant to clinical options, discuss patient perspectives and preferences regarding each option, and arrive at the decision together.17 Shared decision-making is important when treating women with BRCA mutations because there is no single correct plan. Individual values and competing medical issues may strongly guide each woman’s decisions about screening and cancer prevention treatment decisions.
Continue to: Shared decision-making in this situation...
Shared decision-making in this situation is a strategy to use the evidence of risk along with patient preferences around fertility issues to help come to a decision that is the right one for the patient. Primary care clinicians aware of the general risks and benefits of each available option can refer women at high risk for breast or ovarian cancer to a specialist multidisciplinary clinic that can provide tailored risk assessment and risk reduction counseling as needed.18-20
Genetic screening recommendations
Screening is recommended for women who have any 1 of several family risk factors (TABLE 221). A number of risk assessment tools are available for primary care clinicians to determine which patients are at high enough risk for a hereditary breast or ovarian cancer to warrant referral to a genetic counselor.22-25 If screening suggests high risk, the US Preventive Services Task Force (USPSTF) recommends (Grade B) referral for genetic counseling.21
Explain to patients who are candidates for further investigation that a genetic counselor will review their family history and recommend testing for the specific mutations that increase cancer risk. Discuss potential benefits and harms of genetic testing. A benefit of genetic testing is that aggressive screening may suggest preventive procedures to reduce the risk of future cancer. Most tests come back definitively positive or negative, but an indeterminate result may cause harm. A small minority of results may indicate a genetic variant of unknown significance. The ramifications of this variant may not be known. Some women will experience anxiety about nonspecific test results and will be afraid to share them with family members. There is also some concern about privacy issues, potential insurance bias, and coverage of any preventive strategies.26
CASE
Based on Ms. T’s family history and her desire to know more, we referred her to a genetic counselor and she decided to undergo genetic testing. She screened positive for BRCA1. Ms. T was in a serious relationship and thought she would like to have children at some point. She returned to our office after receiving the positive genetic test results, wondering about screening for breast and ovarian cancer.
Breast cancer screening and risk-reduction strategies
Screening. Because the risk of breast cancer is high in women with BRCA mutations, and because cancer in these women is more likely to be advanced at diagnosis, starting a screening program at an early age is prudent. Observational studies suggest that breastfeeding reduces the risk of breast and ovarian cancer in women with BRCA mutations, as it does for women in the general population.27 Women should return for a clinical breast exam every 6 to 12 months starting at age 25; they should start radiologic screening with magnetic resonance imaging at age 25 and mammography at age 30 (TABLE 327,28).
Continue to: Risk-reduction strategies
Risk-reduction strategies. There is weak evidence to support the use of tamoxifen or other synthetic estrogen reuptake modulators (SERMs) to reduce breast cancer risk in women with BRCA mutations. Many of these cancers do not express estrogen receptors, which may explain the lack of efficacy in certain cases. Several observational studies have shown that tamoxifen can reduce the risk of contralateral breast cancer in women with BRCA mutations who have already been diagnosed with cancer in the other breast.29-31 However, tamoxifen does not reduce a patient’s risk of ovarian cancer, and it may increase her risk of uterine cancer.
Prophylactic bilateral mastectomy is the mainstay of breast cancer prevention in this population. Data from a systematic review suggest that this surgery may prevent the incidence of breast cancer in women with BRCA mutations by 90% to 95%.32 However, this review did not demonstrate a reduction in mortality from breast cancer, likely due to poor data quality.32 The National Comprehensive Cancer Network (NCCN) recommends discussing prophylactic mastectomy with all women who have BRCA mutations.28 Further conversations are important to review the risk of tissue left behind and quality-of-life issues, including the inability to breastfeed if the woman wants more children and the cosmetic changes with reconstruction.
Ovarian cancer screening and risk-reduction strategies
Screening. No effective screening strategy has been endorsed for ovarian cancer, as most previous studies have shown screening to be ineffective.26,33 Recently, studies both in the United Kingdom and the United States have investigated a screening strategy using the risk-of-ovarian-cancer algorithm (ROCA), which calculates an individual’s risk based on serum levels of cancer antigen 125 (CA-125).34,35 These studies measured CA-125 levels every 3 to 4 months followed by transvaginal ultrasound if CA-125 increased substantially (as determined by ROCA). Absent an abnormal increase in CA-125, transvaginal ultrasound was performed annually. These screening strategies showed improved specificity over annual screening programs, and the cancers detected were more likely to be diagnosed at an early stage (stage II vs stage III) and had higher rates of zero residual disease after surgery compared with those detected 1 year after screening ended.34,35 However, survival data are not yet available. More research is needed to determine if more frequent screening approaches could improve survival in high-risk women.
NCCN and the American College of Obstetricians and Gynecologists (ACOG) do not endorse routine screening with transvaginal ultrasound and serum CA-125 for high-risk women, as the benefits are uncertain. However, they do advise that these screens may be considered as a short-term strategy for women ages 30 to 35 who defer risk-reducing surgery.26,36 The USPSTF does not make a recommendation regarding ovarian cancer screening in high-risk women.37
Risk-reduction strategies. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only recommended technique for reducing the risk of ovarian cancer in women at high risk.26,33,36 Meta-analyses have shown an 80% reduction in ovarian cancer risk16 and 68% reduction in all-cause mortality with this approach.38 The NCCN recommends RRSO for women with a known BRCA1 mutation between the ages of 35 and 40 who have completed childbearing.36 Since the onset of ovarian cancer tends to be later in women with BRCA2 mutations, it is reasonable to delay RRSO until age 40 to 45 in this population if they have taken other steps to maximize breast cancer prevention (ie, bilateral mastectomy).36
Continue to: Adverse effects of RRSO...
Adverse effects of RRSO include surgery complications (wound infection, small bowel obstruction, bladder perforation) and effects of early menopause (vasomotor symptoms, decreased sexual functioning, and increased risk of osteoporosis, cardiovascular disease, and all-cause mortality).39-41 In the absence of contraindications, ACOG recommends using hormone therapy in women undergoing RRSO until the natural age of menopause,42 particularly if their breast tissue has been removed.
Salpingectomy as an alternative. In an attempt to reduce these adverse effects of early menopause, and because a large proportion of high-grade serous tumors originate in the fallopian tube,43 interest has increased in the use of risk-reducing salpingectomy (removal of fallopian tubes) and delayed oophorectomy in women at high risk of ovarian cancer.42 Studies have shown this may be a cost-effective approach and an acceptable alternative in BRCA mutation carriers who are unwilling to undergo RRSO.44,45 A clinical trial investigating this approach in women with BRCA mutations is currently underway in the United States.46 Many centers offer salpingectomy to high-risk patients < 40 years old, understanding that ovary removal is an eventuality for these patients.
When oral contraceptive pills might be beneficial. In younger women with BRCA mutations, there may also be a role for oral contraceptive pills (OCPs) as a risk-reducing strategy. Meta-analyses have shown an approximately 50% reduction in the risk of ovarian cancer among women with BRCA mutations who use OCPs.47-49
ACOG advises that it is appropriate for women with BRCA mutations to use oral contraceptives if indicated (for pregnancy prevention or menstrual cycle regulation), and that it is reasonable to use them for cancer prevention.26 NCCN does not make a formal recommendation, although it does state OCPs may reduce the risk of ovarian cancer in women with a BRCA mutation.36 Case-control studies have produced conflicting data on the association between OCP use and breast cancer risk in BRCA mutation carriers,50-53 although 2 meta-analyses found no significant association in this population.47,48
Decision aids for women with BRCA mutations
Decision aids are visual displays of risk that help patients work through complex decisions. Most decision aids are in print or digital format and include information about the decision to be made as well as pictorial examples of possible outcomes. Pictographs are especially helpful in communicating information. Some decision aids for women with BRCA mutations can be complicated with multiple outcomes (ie, breast cancer and ovarian cancer) and multiple potential interventions (risk-reducing surgery, enhanced screening options).54
Continue to: A Cochrane review...
A Cochrane review found that decision aids increased patients’ knowledge, helped patients clarify their values, and may improve value-concordant decisions.55 Two papers describing the use of decision aids for women with BRCA mutations56,57 documented decreased decisional conflict and increased satisfaction.
CASE
Ms. T underwent the recommended mammogram and MRI screening for breast cancer, as well as testing with serum CA-125 and ultrasound examinations for ovarian cancer. Her initial mammogram and MRI revealed early stage, triple-negative right breast cancer. She chose to undergo bilateral mastectomy and reconstruction. She has now completed treatment and continues to work closely with her oncology team for appropriate breast follow-up.
One year after her initial diagnosis, at the age of 35, she returned to discuss fertility. She was recently married, and she and her husband wanted to start having children. She was concerned about a safe timeline for her to pursue pregnancy, saying she felt “like a ticking time-bomb” given her prior cancer and carrier status. She wanted to discuss the risks and benefits of pregnancy and when she should consider prophylactic oophorectomy. She had a few options. She could have a baby and then undergo an RRSO, or she could talk to her gynecologist about having a salpingectomy to reduce her risk now and use assisted reproductive technology to get pregnant. She could also freeze eggs or embryos, have an RRSO, and then use a surrogate to get pregnant. We informed her that pregnancy would not affect her risk of ovarian cancer and discussed the options for pre-implantation genetic testing to assure that her children would not carry the genetic mutation.58
We provided Ms. T and her husband with a decision aid to help them navigate the decision. They are currently evaluating the options and said they would let us know when they made a decision.
CORRESPONDENCE
Sarina Schrager, MD, MS, Northeast Family Medicine Center, 3209 Dryden Drive, Madison, WI, 53704; [email protected].
CASE
Sara T* recently moved back to the area to be closer to her family. The 34-year-old patient visited our office to discuss the benefits and potential risks of genetic counseling. She explained that her aunt had just died at age 64 of ovarian cancer. Also, her maternal cousin had been diagnosed at age 42 with breast cancer, and her maternal grandmother had died at age 45 of an unknown “female cancer.” She was scared to find out if she had high-risk genes because she felt it would change her life forever. However, if she ignored the issue, she thought she might worry too much.
We discussed the implications of a positive result, such as having to live with the knowledge and to make decisions about potential screening and risk-reducing surgery. On the other hand, not knowing could allow for the undetected growth of cancer that might otherwise be mitigated to some degree if she knew her risk status and pursued an aggressive screening program.
We worked with Ms. T to map out her next steps.
*The patient’s name has been changed to protect her identity.
Breast cancer is the most commonly diagnosed cancer in women worldwide, representing nearly one-quarter of all female cancer diagnoses in 2018.1 It is the second-leading cause of cancer death in women in developed nations and the leading cause of cancer death in women in developing nations.1 In the United States, 1 in 8 women will develop breast cancer in her lifetime.2 By comparison, the rate of ovarian cancer is much lower, with a lifetime prevalence of 1 in 70 to 80 women.3,4 Although ovarian cancer is less common than breast cancer, its associated mortality is high, and most cases are discovered at advanced stages.
The outsized threat of BRCA mutations. It is estimated that 5% to 10% of all breast cancers are hereditary, with 80% of these attributable to BRCA1 (45%) and BRCA2 (35%).5 These autosomal dominant mutations occur at the germline level, within the egg or sperm, and are therefore incorporated into the DNA of every cell and passed from one generation to the next. Families with BRCA mutations have much higher lifetime rates of cancer. The lifetime risk of breast cancer due to BRCA mutations is estimated at > 80% (BRCA1) and 45% (BRCA2).5BRCA mutations account for between
Male BRCA carriers have a lifetime breast cancer risk of 1% to 5% with BRCA1 and 5% to 10% with BRCA2,7,8 compared with about 1:1000 lifetime incidence in the unselected male population. Male carriers are also at risk for more aggressive prostate cancers.7,8
Continue to: Certain populatiosn carry undue burden of BRCA-related disease
Certain populations carry undue burden of BRCA-related disease due to specific founder mutations. While the estimated global prevalence of BRCA mutations is 0.2% to 1%, for those of Ashkenazi Jewish descent the range is 2% to 3%, representing a relative risk up to 15 times that of the general population.9 Hispanic Americans also appear to have higher rates of BRCA-related cancers.10 Ongoing genetics research continues to identify founder mutations worldwide,10 which may inform future screening guidelines.
In addition to BRCA mutations, there are other, less common mutations (TABLE 15) known to cause hereditary breast and ovarian cancer.
Identifying BRCA genes enables treatment planning. Compared with sporadic cancers, BRCA-related breast cancers
Similarly, BRCA-related ovarian cancer is more likely to be high-grade and endometrioid or serous subtype.14
Shared decision-making helps give clarity to the way forward
Shared decision-making is a process of communication whereby the clinician and the patient identify a decision to be made, review data relevant to clinical options, discuss patient perspectives and preferences regarding each option, and arrive at the decision together.17 Shared decision-making is important when treating women with BRCA mutations because there is no single correct plan. Individual values and competing medical issues may strongly guide each woman’s decisions about screening and cancer prevention treatment decisions.
Continue to: Shared decision-making in this situation...
Shared decision-making in this situation is a strategy to use the evidence of risk along with patient preferences around fertility issues to help come to a decision that is the right one for the patient. Primary care clinicians aware of the general risks and benefits of each available option can refer women at high risk for breast or ovarian cancer to a specialist multidisciplinary clinic that can provide tailored risk assessment and risk reduction counseling as needed.18-20
Genetic screening recommendations
Screening is recommended for women who have any 1 of several family risk factors (TABLE 221). A number of risk assessment tools are available for primary care clinicians to determine which patients are at high enough risk for a hereditary breast or ovarian cancer to warrant referral to a genetic counselor.22-25 If screening suggests high risk, the US Preventive Services Task Force (USPSTF) recommends (Grade B) referral for genetic counseling.21
Explain to patients who are candidates for further investigation that a genetic counselor will review their family history and recommend testing for the specific mutations that increase cancer risk. Discuss potential benefits and harms of genetic testing. A benefit of genetic testing is that aggressive screening may suggest preventive procedures to reduce the risk of future cancer. Most tests come back definitively positive or negative, but an indeterminate result may cause harm. A small minority of results may indicate a genetic variant of unknown significance. The ramifications of this variant may not be known. Some women will experience anxiety about nonspecific test results and will be afraid to share them with family members. There is also some concern about privacy issues, potential insurance bias, and coverage of any preventive strategies.26
CASE
Based on Ms. T’s family history and her desire to know more, we referred her to a genetic counselor and she decided to undergo genetic testing. She screened positive for BRCA1. Ms. T was in a serious relationship and thought she would like to have children at some point. She returned to our office after receiving the positive genetic test results, wondering about screening for breast and ovarian cancer.
Breast cancer screening and risk-reduction strategies
Screening. Because the risk of breast cancer is high in women with BRCA mutations, and because cancer in these women is more likely to be advanced at diagnosis, starting a screening program at an early age is prudent. Observational studies suggest that breastfeeding reduces the risk of breast and ovarian cancer in women with BRCA mutations, as it does for women in the general population.27 Women should return for a clinical breast exam every 6 to 12 months starting at age 25; they should start radiologic screening with magnetic resonance imaging at age 25 and mammography at age 30 (TABLE 327,28).
Continue to: Risk-reduction strategies
Risk-reduction strategies. There is weak evidence to support the use of tamoxifen or other synthetic estrogen reuptake modulators (SERMs) to reduce breast cancer risk in women with BRCA mutations. Many of these cancers do not express estrogen receptors, which may explain the lack of efficacy in certain cases. Several observational studies have shown that tamoxifen can reduce the risk of contralateral breast cancer in women with BRCA mutations who have already been diagnosed with cancer in the other breast.29-31 However, tamoxifen does not reduce a patient’s risk of ovarian cancer, and it may increase her risk of uterine cancer.
Prophylactic bilateral mastectomy is the mainstay of breast cancer prevention in this population. Data from a systematic review suggest that this surgery may prevent the incidence of breast cancer in women with BRCA mutations by 90% to 95%.32 However, this review did not demonstrate a reduction in mortality from breast cancer, likely due to poor data quality.32 The National Comprehensive Cancer Network (NCCN) recommends discussing prophylactic mastectomy with all women who have BRCA mutations.28 Further conversations are important to review the risk of tissue left behind and quality-of-life issues, including the inability to breastfeed if the woman wants more children and the cosmetic changes with reconstruction.
Ovarian cancer screening and risk-reduction strategies
Screening. No effective screening strategy has been endorsed for ovarian cancer, as most previous studies have shown screening to be ineffective.26,33 Recently, studies both in the United Kingdom and the United States have investigated a screening strategy using the risk-of-ovarian-cancer algorithm (ROCA), which calculates an individual’s risk based on serum levels of cancer antigen 125 (CA-125).34,35 These studies measured CA-125 levels every 3 to 4 months followed by transvaginal ultrasound if CA-125 increased substantially (as determined by ROCA). Absent an abnormal increase in CA-125, transvaginal ultrasound was performed annually. These screening strategies showed improved specificity over annual screening programs, and the cancers detected were more likely to be diagnosed at an early stage (stage II vs stage III) and had higher rates of zero residual disease after surgery compared with those detected 1 year after screening ended.34,35 However, survival data are not yet available. More research is needed to determine if more frequent screening approaches could improve survival in high-risk women.
NCCN and the American College of Obstetricians and Gynecologists (ACOG) do not endorse routine screening with transvaginal ultrasound and serum CA-125 for high-risk women, as the benefits are uncertain. However, they do advise that these screens may be considered as a short-term strategy for women ages 30 to 35 who defer risk-reducing surgery.26,36 The USPSTF does not make a recommendation regarding ovarian cancer screening in high-risk women.37
Risk-reduction strategies. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only recommended technique for reducing the risk of ovarian cancer in women at high risk.26,33,36 Meta-analyses have shown an 80% reduction in ovarian cancer risk16 and 68% reduction in all-cause mortality with this approach.38 The NCCN recommends RRSO for women with a known BRCA1 mutation between the ages of 35 and 40 who have completed childbearing.36 Since the onset of ovarian cancer tends to be later in women with BRCA2 mutations, it is reasonable to delay RRSO until age 40 to 45 in this population if they have taken other steps to maximize breast cancer prevention (ie, bilateral mastectomy).36
Continue to: Adverse effects of RRSO...
Adverse effects of RRSO include surgery complications (wound infection, small bowel obstruction, bladder perforation) and effects of early menopause (vasomotor symptoms, decreased sexual functioning, and increased risk of osteoporosis, cardiovascular disease, and all-cause mortality).39-41 In the absence of contraindications, ACOG recommends using hormone therapy in women undergoing RRSO until the natural age of menopause,42 particularly if their breast tissue has been removed.
Salpingectomy as an alternative. In an attempt to reduce these adverse effects of early menopause, and because a large proportion of high-grade serous tumors originate in the fallopian tube,43 interest has increased in the use of risk-reducing salpingectomy (removal of fallopian tubes) and delayed oophorectomy in women at high risk of ovarian cancer.42 Studies have shown this may be a cost-effective approach and an acceptable alternative in BRCA mutation carriers who are unwilling to undergo RRSO.44,45 A clinical trial investigating this approach in women with BRCA mutations is currently underway in the United States.46 Many centers offer salpingectomy to high-risk patients < 40 years old, understanding that ovary removal is an eventuality for these patients.
When oral contraceptive pills might be beneficial. In younger women with BRCA mutations, there may also be a role for oral contraceptive pills (OCPs) as a risk-reducing strategy. Meta-analyses have shown an approximately 50% reduction in the risk of ovarian cancer among women with BRCA mutations who use OCPs.47-49
ACOG advises that it is appropriate for women with BRCA mutations to use oral contraceptives if indicated (for pregnancy prevention or menstrual cycle regulation), and that it is reasonable to use them for cancer prevention.26 NCCN does not make a formal recommendation, although it does state OCPs may reduce the risk of ovarian cancer in women with a BRCA mutation.36 Case-control studies have produced conflicting data on the association between OCP use and breast cancer risk in BRCA mutation carriers,50-53 although 2 meta-analyses found no significant association in this population.47,48
Decision aids for women with BRCA mutations
Decision aids are visual displays of risk that help patients work through complex decisions. Most decision aids are in print or digital format and include information about the decision to be made as well as pictorial examples of possible outcomes. Pictographs are especially helpful in communicating information. Some decision aids for women with BRCA mutations can be complicated with multiple outcomes (ie, breast cancer and ovarian cancer) and multiple potential interventions (risk-reducing surgery, enhanced screening options).54
Continue to: A Cochrane review...
A Cochrane review found that decision aids increased patients’ knowledge, helped patients clarify their values, and may improve value-concordant decisions.55 Two papers describing the use of decision aids for women with BRCA mutations56,57 documented decreased decisional conflict and increased satisfaction.
CASE
Ms. T underwent the recommended mammogram and MRI screening for breast cancer, as well as testing with serum CA-125 and ultrasound examinations for ovarian cancer. Her initial mammogram and MRI revealed early stage, triple-negative right breast cancer. She chose to undergo bilateral mastectomy and reconstruction. She has now completed treatment and continues to work closely with her oncology team for appropriate breast follow-up.
One year after her initial diagnosis, at the age of 35, she returned to discuss fertility. She was recently married, and she and her husband wanted to start having children. She was concerned about a safe timeline for her to pursue pregnancy, saying she felt “like a ticking time-bomb” given her prior cancer and carrier status. She wanted to discuss the risks and benefits of pregnancy and when she should consider prophylactic oophorectomy. She had a few options. She could have a baby and then undergo an RRSO, or she could talk to her gynecologist about having a salpingectomy to reduce her risk now and use assisted reproductive technology to get pregnant. She could also freeze eggs or embryos, have an RRSO, and then use a surrogate to get pregnant. We informed her that pregnancy would not affect her risk of ovarian cancer and discussed the options for pre-implantation genetic testing to assure that her children would not carry the genetic mutation.58
We provided Ms. T and her husband with a decision aid to help them navigate the decision. They are currently evaluating the options and said they would let us know when they made a decision.
CORRESPONDENCE
Sarina Schrager, MD, MS, Northeast Family Medicine Center, 3209 Dryden Drive, Madison, WI, 53704; [email protected].
1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941-1953.
2. SEER Cancer Statistics Review, 1975-2016. Cancer of the female breast. [Table 4.1] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_04_breast.pdf. Accessed May 27, 2020.
3. SEER Cancer Statistics Review, 1975-2016. Cancer of the ovary. [Table 21.10] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_21_ovary.pdf. Accessed May 22, 2020.
4. Torre LA, Trabert B, DeSantis C, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284-296.
5. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4:665-676.
6. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807-2816.
7. Tai YC, Domchek S, Parmigiani G, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99:1811-1814.
8. Evans DG, Susnerwala I, Dawson J, et al. Risk of breast cancer in male BRCA2 carriers. J Med Genet. 2010;47:710-711.
9. CDC. Jewish women and BRCA gene mutations. www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/jewish_women_brca.htm. Accessed May 22, 2020.
10. Rebbeck TR, Friebel TM, Friedman E, et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018;39:593-620.
11. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26:3324–3330.
12. Wang YA, Jian JW, Hung CF, et al. Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer. 2018;18:315.
13. Baretta Z, Mocellin S, Goldin E, et al. Effect of BRCA germline mutations on breast cancer prognosis: a systematic review and meta-analysis. Medicine. 2016;95:e4975.
14. Lakhani SR, Manek S, Penault-Llorca F, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin Cancer Res. 2004;10:2473-2481.
15. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010;22:72-78.
16. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80-87.
17. Elwyn G, Frosch D, Thomson R, et al. Shared decision making: a model for clinical practice. J Gen Int Med. 2012;27:1361-1367.
18. Ardern-Jones A, Eeles R. Developments in clinical practice: follow up clinic for BRCA mutation carriers: a case study highlighting the “virtual clinic.” Hered Cancer Clin Pract. 2004;2:77-79.
19. Yerushalmi R, Rizel S, Zoref D, et al. A dedicated follow-up clinic for BRCA mutation carriers. Isr Med Assoc J. 2016;18:549-552.
20. Pichert G, Jacobs C, Jacobs I, et al. Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. Fam Cancer. 2010;9:313-319.
21. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019;322:652-665.
22. Evans D, Eccles D, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004;41:474-480.
23. Bellcross CA, Lemke AA, Pape LS, et al. Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population. Genet Med. 2009;11:783-789.
24. Hoskins KF, Zwaagstra A, Ranz M. Validation of a tool for identifying women at high risk for hereditary breast cancer in population based screening. Cancer. 2006;107:1769-1776.
25. Gilpin CA, Carson N, Hunter AG. A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center. Clin Genet. 2000;58:299-308.
26. Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No 182: Hereditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol. 2017;130:e110-e126.
27. Paluch-Shimon S, Cardoso F, Sessa C, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27(suppl 5):v103-v110.
28. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast and ovarian. 2019. NCCN Clinical Practice Guidelines in Oncology. www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf. Accessed May 22, 2020.
29. Phillips KA, Milne RL, Rookus MA, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091-3099.
30. Foulkes WD, Goffin J, Brunet JS, et al. Tamoxifen may be an effective adjuvant treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst. 2002;94:1504-1506.
31. Gronwald J, Tung N, Foulkes WD, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281-2284.
32. Ludwig KK, Neuner J, Butler A, et al. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. Am J Surgery. 2016;212:660-669.
33. Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.
34. Rosenthal AN, Fraser LSM, Philpott S, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom Familial Ovarian Cancer Screening Study. J Clin Oncol. 2017;35:1411-1420.
35. Skates SJ, Greene MH, Buys SS, et al. Early detection of ovarian cancer using the Risk of Ovarian Cancer Algorithm with frequent CA125 testing in women at increased familial risk—combined results from two screening trials. Clin Cancer Res. 2017;23:3628-3637.
36. Daly MB, Pilarski R, Berry M, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw. 2017;15:9-20.
37. Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:588-594.
38. Marchetti C, De Felice F, Palaia I, et al. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health. 2014;14:150.
39. Nelson HD, Pappas M, Zakher B, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2014;160:255-266.
40. Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses’ health study. Obstet Gynecol. 2013;121:709-716.
41. Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18:483-491.
42. Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian cancer prevention and screening. Obstet Gynecol. 2018;131:909-927.
43. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3-9.
44. Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol. 2013;121:14-24.
45. Holman LL, Friedman S, Daniels MS, et al. Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecol Oncol. 2014;133:283-286.
46. MD Anderson Cancer Center. Prophylactic salpingectomy with delayed oophorectomy, risk-reducing salpingo-oophorectomy, and ovarian cancer screening among BRCA mutation carriers: a proof-of-concept study. www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2013-0340.html. Accessed May 22, 2020.
47. Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer. 2010;46:2275-2284.
48. Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013;31:4188-4198.
49. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju091.
50. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev. 2006;15:1863-1870.
51. Lee E, Ma H, McKean-Cowdin R, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev. 2008;17:3170-3178.
52. Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94:1773-1779.
53. Milne RL, Knight JA, John EM, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev. 2005;14:350-356.
54. Culver JO, MacDonald DJ, Thornton AA, et al. Development and evaluation of a decision aid for BRCA carriers with breast cancer. J Genet Couns. 2011;20:294-307.
55. Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Syst Rev. 2017;4:CD001431.
56. Schwartz MD, Valdimarsdottir HB, DeMarco TA, et al. Randomized trial of a decision aid for BRCA1/BRCA2 mutation carriers: impact on measures of decision making and satisfaction. Health Psychol. 2009;28:11-19.
57. Metcalfe KA, Dennis CL, Poll A, et al. Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial. Gen Med. 2017;19:330-336.
58. Friedman LC, Kramer RM. Reproductive issues for women with BRCA mutations. J Natl Cancer Inst Monogr. 2005;34:83-86.
1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941-1953.
2. SEER Cancer Statistics Review, 1975-2016. Cancer of the female breast. [Table 4.1] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_04_breast.pdf. Accessed May 27, 2020.
3. SEER Cancer Statistics Review, 1975-2016. Cancer of the ovary. [Table 21.10] National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/sect_21_ovary.pdf. Accessed May 22, 2020.
4. Torre LA, Trabert B, DeSantis C, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284-296.
5. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4:665-676.
6. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807-2816.
7. Tai YC, Domchek S, Parmigiani G, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99:1811-1814.
8. Evans DG, Susnerwala I, Dawson J, et al. Risk of breast cancer in male BRCA2 carriers. J Med Genet. 2010;47:710-711.
9. CDC. Jewish women and BRCA gene mutations. www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/jewish_women_brca.htm. Accessed May 22, 2020.
10. Rebbeck TR, Friebel TM, Friedman E, et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018;39:593-620.
11. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26:3324–3330.
12. Wang YA, Jian JW, Hung CF, et al. Germline breast cancer susceptibility gene mutations and breast cancer outcomes. BMC Cancer. 2018;18:315.
13. Baretta Z, Mocellin S, Goldin E, et al. Effect of BRCA germline mutations on breast cancer prognosis: a systematic review and meta-analysis. Medicine. 2016;95:e4975.
14. Lakhani SR, Manek S, Penault-Llorca F, et al. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers. Clin Cancer Res. 2004;10:2473-2481.
15. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010;22:72-78.
16. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80-87.
17. Elwyn G, Frosch D, Thomson R, et al. Shared decision making: a model for clinical practice. J Gen Int Med. 2012;27:1361-1367.
18. Ardern-Jones A, Eeles R. Developments in clinical practice: follow up clinic for BRCA mutation carriers: a case study highlighting the “virtual clinic.” Hered Cancer Clin Pract. 2004;2:77-79.
19. Yerushalmi R, Rizel S, Zoref D, et al. A dedicated follow-up clinic for BRCA mutation carriers. Isr Med Assoc J. 2016;18:549-552.
20. Pichert G, Jacobs C, Jacobs I, et al. Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers. Fam Cancer. 2010;9:313-319.
21. Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019;322:652-665.
22. Evans D, Eccles D, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004;41:474-480.
23. Bellcross CA, Lemke AA, Pape LS, et al. Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population. Genet Med. 2009;11:783-789.
24. Hoskins KF, Zwaagstra A, Ranz M. Validation of a tool for identifying women at high risk for hereditary breast cancer in population based screening. Cancer. 2006;107:1769-1776.
25. Gilpin CA, Carson N, Hunter AG. A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center. Clin Genet. 2000;58:299-308.
26. Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No 182: Hereditary Breast and Ovarian Cancer Syndrome. Obstet Gynecol. 2017;130:e110-e126.
27. Paluch-Shimon S, Cardoso F, Sessa C, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27(suppl 5):v103-v110.
28. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast and ovarian. 2019. NCCN Clinical Practice Guidelines in Oncology. www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf. Accessed May 22, 2020.
29. Phillips KA, Milne RL, Rookus MA, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091-3099.
30. Foulkes WD, Goffin J, Brunet JS, et al. Tamoxifen may be an effective adjuvant treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst. 2002;94:1504-1506.
31. Gronwald J, Tung N, Foulkes WD, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281-2284.
32. Ludwig KK, Neuner J, Butler A, et al. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. Am J Surgery. 2016;212:660-669.
33. Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.
34. Rosenthal AN, Fraser LSM, Philpott S, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom Familial Ovarian Cancer Screening Study. J Clin Oncol. 2017;35:1411-1420.
35. Skates SJ, Greene MH, Buys SS, et al. Early detection of ovarian cancer using the Risk of Ovarian Cancer Algorithm with frequent CA125 testing in women at increased familial risk—combined results from two screening trials. Clin Cancer Res. 2017;23:3628-3637.
36. Daly MB, Pilarski R, Berry M, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw. 2017;15:9-20.
37. Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:588-594.
38. Marchetti C, De Felice F, Palaia I, et al. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health. 2014;14:150.
39. Nelson HD, Pappas M, Zakher B, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2014;160:255-266.
40. Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses’ health study. Obstet Gynecol. 2013;121:709-716.
41. Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18:483-491.
42. Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian cancer prevention and screening. Obstet Gynecol. 2018;131:909-927.
43. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3-9.
44. Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol. 2013;121:14-24.
45. Holman LL, Friedman S, Daniels MS, et al. Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecol Oncol. 2014;133:283-286.
46. MD Anderson Cancer Center. Prophylactic salpingectomy with delayed oophorectomy, risk-reducing salpingo-oophorectomy, and ovarian cancer screening among BRCA mutation carriers: a proof-of-concept study. www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2013-0340.html. Accessed May 22, 2020.
47. Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer. 2010;46:2275-2284.
48. Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013;31:4188-4198.
49. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju091.
50. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev. 2006;15:1863-1870.
51. Lee E, Ma H, McKean-Cowdin R, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev. 2008;17:3170-3178.
52. Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94:1773-1779.
53. Milne RL, Knight JA, John EM, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev. 2005;14:350-356.
54. Culver JO, MacDonald DJ, Thornton AA, et al. Development and evaluation of a decision aid for BRCA carriers with breast cancer. J Genet Couns. 2011;20:294-307.
55. Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Syst Rev. 2017;4:CD001431.
56. Schwartz MD, Valdimarsdottir HB, DeMarco TA, et al. Randomized trial of a decision aid for BRCA1/BRCA2 mutation carriers: impact on measures of decision making and satisfaction. Health Psychol. 2009;28:11-19.
57. Metcalfe KA, Dennis CL, Poll A, et al. Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial. Gen Med. 2017;19:330-336.
58. Friedman LC, Kramer RM. Reproductive issues for women with BRCA mutations. J Natl Cancer Inst Monogr. 2005;34:83-86.
PRACTICE RECOMMENDATIONS
› Recommend genetic screening for the BRCA mutation if a patient’s family history includes a breast cancer diagnosis before age 50, occurrences of both breast and ovarian cancers, or other suggestive features. C
› Advise women with the BRCA gene to return for a clinical breast exam every 6 to 12 months starting at age 25, and to start radiologic screening at age 30. C
› Consider recommending bilateral salpingo-oophorectomy to prevent ovarian cancer in women 35 to 40 years of age with a BRCA1 mutation who have completed childbearing. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
‘A good and peaceful death’: Cancer hospice during the pandemic
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.