User login
Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
FDA Expands Pembrolizumab Approval for Endometrial Cancer
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has expanded the indication for pembrolizumab (Keytruda, Merck) to include the use of the targeted immunotherapy agent plus chemotherapy followed by single-agent pembrolizumab in adults with primary advanced or recurrent endometrial cancer.
Approval in this setting was granted following priority review and was based on efficacy demonstrated in the randomized, placebo-controlled, phase 3 KEYNOTE-868/NRG-GY018 trial. The multicenter trial showed improved progression-free survival (PFS) with chemotherapy plus pembrolizumab versus chemotherapy plus placebo in patients with stage 3 or 4 disease or stage IVB recurrent disease in two cohorts: 222 patients with mismatch repair (MMR) deficiency, and 588 patients with MMR proficiency.
Among the MMR-deficient patients, median PFS was not reached in the treatment arm and was 6.5 months in the control arm (hazard ratio, 0.30). Among the MMR-proficient patients, the median PFS was 11.1 versus 8.5 months in the study arms, respectively (HR, 0.60), according to an FDA press release.
Patients in both cohorts were randomized 1:1 to receive 200 mg of either pembrolizumab or placebo every 3 weeks, followed by paclitaxel at a dose of 175 mg/m2 and carboplatin at a dose of AUC 5 mg/mL/min for six cycles and then 400 mg of pembrolizumab or placebo every 6 weeks for up to 14 cycles.
“Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash,” the FDA noted.
According to the full prescribing information for pembrolizumab, the recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
A version of this article first appeared on Medscape.com.
Polycystic Ovarian Syndrome: New Science Offers Old Remedy
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
An ancient Chinese remedy for malaria could offer new hope to the 10% of reproductive-age women living with polycystic ovarian syndrome (PCOS), a poorly understood endocrine disorder that can cause hormonal imbalances, irregular periods, and cysts in the ovaries.
“PCOS is among the most common disorders of reproductive-age women,” said endocrinologist Andrea Dunaif, MD, a professor at the Icahn School of Medicine at Mount Sinai, New York City, who studies diabetes and women’s health. “It is a major risk factor for obesity, type 2 diabetes, and heart disease.” It’s also a leading cause of infertility.
Yet despite how common it is, PCOS has no Food and Drug Administration–approved treatments, though a few early-stage clinical trials are underway. Many women end up taking off-label medications such as oral contraceptives, insulin-sensitizing agents, and antiandrogens to help manage symptoms. Surgery can also be used to treat fertility problems associated with PCOS, though it may not work for everyone.
In a new study, a derivative of artemisinin — a molecule that comes from Artemisia plants, which have been used as far back as 1596 to treat malaria in China — helped relieve PCOS symptoms in rats and a small group of women.
Previously, the study’s lead researcher Qi-qun Tang, MD, PhD, had found that this derivative, called artemether, can increase thermogenesis, boosting metabolism. Dr. Tang and his team at Fudan University, Shanghai, China, wanted to see if it would help with PCOS, which is associated with metabolic problems such as insulin resistance.
What the Researchers Did
To simulate PCOS in rats, the team treated the rodents with insulin and human chorionic gonadotropin. Then, they tested artemether on the rats and found that it lowered androgen production in the ovaries.
“A common feature [of PCOS] is that the ovaries, and often the adrenal glands, make increased male hormones, nowhere near what a man makes but slightly above what a normal woman makes,” said Dr. Dunaif, who was not involved in the study.
Artemether “inhibits one of the steroidogenic enzymes, CYP11A1, which is important in the production of male hormones,” Dr. Tang said. It does this by increasing the enzyme’s interaction with a protein called LONP1, triggering the enzyme’s breakdown. Increased levels of LONP1 also appeared to suppress androgen production in the ovaries.
In a pilot clinical study of 19 women with PCOS, taking dihydroartemisinin — an approved drug used to treat malaria that contains active artemisinin derivatives — for 12 weeks substantially reduced serum testosterone and anti-Müllerian hormone levels (which are higher in women with PCOS). Using ultrasound, the researchers found that the antral follicle count (also higher than normal with PCOS) had been reduced. All participants had regular menstrual cycles during treatment. And no one reported significant side effects.
“Regular menstrual cycles suggest that there is ovulation, which can result in conception,” Dr. Dunaif said. Still, testing would be needed to confirm that cycles are ovulatory.
Lowering androgen levels “could improve a substantial portion of the symptoms of PCOS,” said Dr. Dunaif. But the research didn’t see an improvement in insulin sensitivity among the women, suggesting that targeting androgens may not help the metabolic symptoms.
What’s Next?
A larger, placebo-controlled trial would still be needed to assess the drug’s efficacy, said Dr. Dunaif, pointing out that the human study did not have a placebo arm.
And unanswered questions remain. Are there any adrenal effects of the compound? “The enzymes that produce androgens are shared between the ovary and the adrenal [gland],” Dr. Dunaif said, but she pointed out that the study doesn’t address whether there is an adrenal benefit. It’s something to look at in future research.
Still, because artemisinin is an established drug, it may come to market faster than a new molecule would, she said. However, a pharmaceutical company would need to be willing to take on the drug. (Dr. Tang said several companies have already expressed interest.)
And while you can buy artemisinin on the Internet, Dr. Dunaif warned not to start taking it if you have PCOS. “I don’t think we’re at that point,” Dr. Dunaif said.
A version of this article first appeared on Medscape.com.
FROM SCIENCE
Surviving to Thriving: Enhancing Quality of Life in Breast Cancer
Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.
According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.
As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.
The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.
Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.
Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.
Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources.
There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
Surveilling and Mitigating Recurrence
Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.
While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.
Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.
These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.
Yet, that may change in the coming years, he told attendees.
Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.
These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence.
He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.
The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk.
Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.
Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.
Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.
A version of this article first appeared on Medscape.com.
Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.
According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.
As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.
The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.
Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.
Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.
Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources.
There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
Surveilling and Mitigating Recurrence
Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.
While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.
Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.
These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.
Yet, that may change in the coming years, he told attendees.
Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.
These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence.
He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.
The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk.
Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.
Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.
Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.
A version of this article first appeared on Medscape.com.
Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.
According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.
As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.
The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.
Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.
Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.
Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources.
There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
Surveilling and Mitigating Recurrence
Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.
While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.
Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.
These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.
Yet, that may change in the coming years, he told attendees.
Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.
These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence.
He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.
The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk.
Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.
Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.
Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.
A version of this article first appeared on Medscape.com.
FROM ASCO 2024
Recurrent UTI Rates High Among Older Women, Diagnosing Accurately Is Complicated
TOPLINE:
Accurately diagnosing recurrent urinary tract infections (rUTIs) in older women is challenging and requires careful weighing of the risks and benefits of various treatments, according to a new clinical insight published in JAMA Internal Medicine.
METHODOLOGY:
- Women aged > 65 years have double the rUTI rates compared with younger women, but detecting the condition is more complicated due to age-related conditions, such as overactive bladder related to menopause.
- Overuse of antibiotics can increase their risk of contracting antibiotic-resistant organisms and can lead to pulmonary or hepatic toxic effects in women with reduced kidney function.
- Up to 20% of older women have bacteria in their urine, which may or may not reflect a rUTI.
- Diagnosing rUTIs is complicated if women have dementia or cognitive decline, which can hinder recollection of symptoms.
TAKEAWAYS:
- Clinicians should consider only testing older female patients for rUTIs when symptoms are present and consider all possibilities before making a diagnosis.
- Vaginal estrogen may be an effective treatment, although the authors of the clinical review note a lack of a uniform formulation to recommend. However, oral estrogen use is not supported by evidence, and clinicians should instead consider vaginal creams or rings.
- The drug methenamine may be as effective as antibiotics but may not be safe for women with comorbidities. Evidence supports daily use at 1 g.
- Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
IN PRACTICE:
“Shared decision-making is especially important when diagnosis of an rUTI episode in older women is unclear ... in these cases, clinicians should acknowledge limitations in the evidence and invite patients or their caregivers to discuss preferences about presumptive treatment, weighing the possibility of earlier symptom relief or decreased UTI complications against the risk of adverse drug effects or multidrug resistance.”
SOURCE:
The paper was led by Alison J. Huang, MD, MAS, an internal medicine specialist and researcher in the Department of Medicine at the University of California, San Francisco.
LIMITATIONS:
The authors reported no limitations.
DISCLOSURES:
Dr. Huang received grants from the National Institutes of Health. Other authors reported receiving grants from the Agency for Healthcare Research and Quality, the US Department of Veterans Affairs, the Kahn Foundation, and Nanovibronix.
Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
A version of this article first appeared on Medscape.com.
TOPLINE:
Accurately diagnosing recurrent urinary tract infections (rUTIs) in older women is challenging and requires careful weighing of the risks and benefits of various treatments, according to a new clinical insight published in JAMA Internal Medicine.
METHODOLOGY:
- Women aged > 65 years have double the rUTI rates compared with younger women, but detecting the condition is more complicated due to age-related conditions, such as overactive bladder related to menopause.
- Overuse of antibiotics can increase their risk of contracting antibiotic-resistant organisms and can lead to pulmonary or hepatic toxic effects in women with reduced kidney function.
- Up to 20% of older women have bacteria in their urine, which may or may not reflect a rUTI.
- Diagnosing rUTIs is complicated if women have dementia or cognitive decline, which can hinder recollection of symptoms.
TAKEAWAYS:
- Clinicians should consider only testing older female patients for rUTIs when symptoms are present and consider all possibilities before making a diagnosis.
- Vaginal estrogen may be an effective treatment, although the authors of the clinical review note a lack of a uniform formulation to recommend. However, oral estrogen use is not supported by evidence, and clinicians should instead consider vaginal creams or rings.
- The drug methenamine may be as effective as antibiotics but may not be safe for women with comorbidities. Evidence supports daily use at 1 g.
- Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
IN PRACTICE:
“Shared decision-making is especially important when diagnosis of an rUTI episode in older women is unclear ... in these cases, clinicians should acknowledge limitations in the evidence and invite patients or their caregivers to discuss preferences about presumptive treatment, weighing the possibility of earlier symptom relief or decreased UTI complications against the risk of adverse drug effects or multidrug resistance.”
SOURCE:
The paper was led by Alison J. Huang, MD, MAS, an internal medicine specialist and researcher in the Department of Medicine at the University of California, San Francisco.
LIMITATIONS:
The authors reported no limitations.
DISCLOSURES:
Dr. Huang received grants from the National Institutes of Health. Other authors reported receiving grants from the Agency for Healthcare Research and Quality, the US Department of Veterans Affairs, the Kahn Foundation, and Nanovibronix.
Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
A version of this article first appeared on Medscape.com.
TOPLINE:
Accurately diagnosing recurrent urinary tract infections (rUTIs) in older women is challenging and requires careful weighing of the risks and benefits of various treatments, according to a new clinical insight published in JAMA Internal Medicine.
METHODOLOGY:
- Women aged > 65 years have double the rUTI rates compared with younger women, but detecting the condition is more complicated due to age-related conditions, such as overactive bladder related to menopause.
- Overuse of antibiotics can increase their risk of contracting antibiotic-resistant organisms and can lead to pulmonary or hepatic toxic effects in women with reduced kidney function.
- Up to 20% of older women have bacteria in their urine, which may or may not reflect a rUTI.
- Diagnosing rUTIs is complicated if women have dementia or cognitive decline, which can hinder recollection of symptoms.
TAKEAWAYS:
- Clinicians should consider only testing older female patients for rUTIs when symptoms are present and consider all possibilities before making a diagnosis.
- Vaginal estrogen may be an effective treatment, although the authors of the clinical review note a lack of a uniform formulation to recommend. However, oral estrogen use is not supported by evidence, and clinicians should instead consider vaginal creams or rings.
- The drug methenamine may be as effective as antibiotics but may not be safe for women with comorbidities. Evidence supports daily use at 1 g.
- Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
IN PRACTICE:
“Shared decision-making is especially important when diagnosis of an rUTI episode in older women is unclear ... in these cases, clinicians should acknowledge limitations in the evidence and invite patients or their caregivers to discuss preferences about presumptive treatment, weighing the possibility of earlier symptom relief or decreased UTI complications against the risk of adverse drug effects or multidrug resistance.”
SOURCE:
The paper was led by Alison J. Huang, MD, MAS, an internal medicine specialist and researcher in the Department of Medicine at the University of California, San Francisco.
LIMITATIONS:
The authors reported no limitations.
DISCLOSURES:
Dr. Huang received grants from the National Institutes of Health. Other authors reported receiving grants from the Agency for Healthcare Research and Quality, the US Department of Veterans Affairs, the Kahn Foundation, and Nanovibronix.
Cranberry supplements and behavioral changes may be helpful, but evidence is limited, including among women living in long-term care facilities.
A version of this article first appeared on Medscape.com.
Could British Columbia Eliminate Cervical Cancer by 2031?
To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.
The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.
“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.
Three’s a Charm
The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.
Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.
The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).
Low Incidence, Strained System
The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.
“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.
“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.
Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.
“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.
In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.
Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”
The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.
The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.
“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.
Three’s a Charm
The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.
Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.
The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).
Low Incidence, Strained System
The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.
“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.
“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.
Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.
“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.
In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.
Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”
The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.
The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.
“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.
Three’s a Charm
The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.
Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.
The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).
Low Incidence, Strained System
The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.
“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.
“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.
Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.
“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.
In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.
Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”
The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Ovarian Cancer Risk Doubled by Estrogen-Only HRT
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
FROM ASCO 2024
HPV Vaccine Offers Cancer Protection Beyond Cervical Cancer
The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.
“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”
Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.
HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.
HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.
Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).
“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.
“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.
Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.
“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”
Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.
The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.
A version of this article appeared on Medscape.com .
The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.
“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”
Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.
HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.
HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.
Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).
“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.
“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.
Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.
“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”
Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.
The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.
A version of this article appeared on Medscape.com .
The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.
“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”
Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.
HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.
HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.
Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).
“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.
“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.
Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.
“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”
Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.
The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.
A version of this article appeared on Medscape.com .
FROM ASCO 2024
About 20% of Breast Cancer Survivors Gain Excess Weight
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.
Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time.
“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”
Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.
In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.
Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.
At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).
However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.
After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.
Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production.
Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.
“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”
“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”
Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ENDO 2024
Fine Particulate Matter Raises Type 2 Diabetes Risk in Women
TOPLINE:
Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.
METHODOLOGY:
- Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
- Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
- They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
- The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
- The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m3) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m3).
TAKEAWAY:
- The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m3, respectively, exceeding the WHO limit by more than 13-fold.
- Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m3 raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
- Long-term exposure to PM2.5 > 5 µg/m3 and 35 µg/m3 in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
- A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).
IN PRACTICE:
“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.
SOURCE:
The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.
LIMITATIONS:
An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.
DISCLOSURES:
The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.
METHODOLOGY:
- Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
- Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
- They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
- The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
- The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m3) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m3).
TAKEAWAY:
- The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m3, respectively, exceeding the WHO limit by more than 13-fold.
- Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m3 raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
- Long-term exposure to PM2.5 > 5 µg/m3 and 35 µg/m3 in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
- A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).
IN PRACTICE:
“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.
SOURCE:
The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.
LIMITATIONS:
An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.
DISCLOSURES:
The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Long-term exposure to fine particulate matter is associated with higher fasting blood glucose (FBG) levels and an increased type 2 diabetes risk, significantly contributing to the diabetes-related health burden among women of reproductive age.
METHODOLOGY:
- Exposure to fine particulate matter < 2.5 µm (PM2.5) is a known risk factor for type 2 diabetes, but its effect on women of reproductive age, who undergo hormonal fluctuations during reproductive events, is not well studied.
- Researchers evaluated the association of long-term exposure to PM2.5 with FBG levels and diabetes risk in 20,076,032 eligible women of reproductive age (average age, 27.04 years) across 350 cities in China between 2010 and 2015.
- They assessed PM2.5 exposure at the participants’ residential addresses and calculated average long-term exposure at 1 (lag 1 year), 2 (lag 2 years), and 3 years (lag 3 years) before the survey date, as defined by the World Health Organization (WHO).
- The primary outcomes were FBG levels and diabetes prevalence (FBG, ≥ 7 mmol/L, classified as diabetes; FBG, 6.1-7 mmol/L, classified as prediabetes).
- The study also evaluated the diabetes burden attributed to long-term PM2.5 exposure as per the Chinese National Ambient Air Quality Standards (annual mean PM2.5 exposure limit, > 35 µg/m3) and the WHO air quality guideline (annual mean PM2.5 exposure limit, > 5 µg/m3).
TAKEAWAY:
- The median PM2.5 exposure levels over lag periods of 1, 2, and 3 years were 67, 67, and 66 µg/m3, respectively, exceeding the WHO limit by more than 13-fold.
- Each interquartile range increase in the 3-year average PM2.5 exposure by 27 μg/m3 raised FBG levels by 0.078 mmol/L (P < .05), risk for diabetes by 18% (odds ratio [OR], 1.18; 95% CI, 1.16-1.19), and risk for prediabetes by 5% (OR, 1.05; 95% CI, 1.04-1.05).
- Long-term exposure to PM2.5 > 5 µg/m3 and 35 µg/m3 in the previous 3 years corresponded to an additional 41.7 (95% CI, 39.3-44.0) and 78.6 (95% CI, 74.5-82.6) thousand cases of diabetes nationwide, respectively.
- A higher PM2.5 exposure increased FBG levels and risk for diabetes in women with overweight or obesity vs those without and in those aged ≥ 35 years vs < 35 years (P < .001).
IN PRACTICE:
“These findings carry significant public health implications for formulating effective intervention strategies and environmental policies to better protect women’s health, particularly in countries with relatively high levels of air pollution and a large population with diabetes, such as China,” the authors wrote.
SOURCE:
The study, led by Yang Shen, Key Laboratory of Public Health Safety of the Ministry of Education and National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China, was published online in Diabetes Care.
LIMITATIONS:
An error in the measurement of particulate matter exposure may have been possible as residential address estimates were used as a proxy for actual personal exposure. Questionnaires were used to retrospectively collect information on parameters such as smoking and alcohol consumption, which may have introduced recall bias. Data on potential confounders, such as diet and physical activity, were not included. Distinction between type 1 and type 2 diabetes was not reported owing to data collection–related limitations.
DISCLOSURES:
The study was supported by the National Key Research and Development Program of China, Henan Key Research and Development Program, State Key Laboratory of Resources and Environmental Information System, and Three-Year Public Health Action Plan of Shanghai. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.