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Actionable mutations more likely in women with both breast and uterine cancer
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
FROM GYNECOLOGIC ONCOLOGY
Key clinical point: Women with both breast and uterine cancer are more likely to carry actionable mutations than do women with breast or uterine cancer alone.
Major finding: At least one actionable mutation was seen in 14% of women with breast and uterine cancer, compared with 9.3% of women with breast cancer only, 11.5% of women with uterine cancer only, and 6.8% of women with no personal cancer history.
Study details: A retrospective analysis of a cohort of nearly 52,000 patients who underwent multigene panel testing.
Disclosures: Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics.
Source: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
FDA approves olaparib for maintenance treatment of BRCA-mutated advanced ovarian cancer
The Food and Drug Administration has approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy. 
The FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories) to identify patients who are eligible for olaparib.
Approval of olaparib was based on improvement in progression-free survival (PFS) in the phase 3 SOLO-1 trial of 391 women with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer following first-line, platinum-based chemotherapy. Patients were randomized (2:1) to receive olaparib tablets 300 mg orally twice daily or placebo.
Estimated median investigator-assessed PFS was not reached in the olaparib arm and was 13.8 months in the placebo arm (hazard ratio, 0.30; 95% confidence interval, 0.23-0.41; P less than .0001). Overall survival data are not yet mature.
The most common adverse reactions in women who received olaparib in SOLO-1 were nausea, fatigue, abdominal pain, vomiting, anemia, diarrhea, upper respiratory tract infection/influenza/nasopharyngitis/bronchitis, constipation, dysgeusia, decreased appetite, dizziness, neutropenia, dyspepsia, dyspnea, urinary tract infection, leukopenia, thrombocytopenia, and stomatitis.
The recommended olaparib dose is 300 mg (two 150 mg tablets) taken orally twice daily, with or without food, for a total daily dose of 600 mg, the FDA said in a press statement.
Olaparib is marketed as Lynparza by AstraZeneca Pharmaceuticals.
The Food and Drug Administration has approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.
The FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories) to identify patients who are eligible for olaparib.
Approval of olaparib was based on improvement in progression-free survival (PFS) in the phase 3 SOLO-1 trial of 391 women with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer following first-line, platinum-based chemotherapy. Patients were randomized (2:1) to receive olaparib tablets 300 mg orally twice daily or placebo.
Estimated median investigator-assessed PFS was not reached in the olaparib arm and was 13.8 months in the placebo arm (hazard ratio, 0.30; 95% confidence interval, 0.23-0.41; P less than .0001). Overall survival data are not yet mature.
The most common adverse reactions in women who received olaparib in SOLO-1 were nausea, fatigue, abdominal pain, vomiting, anemia, diarrhea, upper respiratory tract infection/influenza/nasopharyngitis/bronchitis, constipation, dysgeusia, decreased appetite, dizziness, neutropenia, dyspepsia, dyspnea, urinary tract infection, leukopenia, thrombocytopenia, and stomatitis.
The recommended olaparib dose is 300 mg (two 150 mg tablets) taken orally twice daily, with or without food, for a total daily dose of 600 mg, the FDA said in a press statement.
Olaparib is marketed as Lynparza by AstraZeneca Pharmaceuticals.
The Food and Drug Administration has approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.
The FDA also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories) to identify patients who are eligible for olaparib.
Approval of olaparib was based on improvement in progression-free survival (PFS) in the phase 3 SOLO-1 trial of 391 women with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer following first-line, platinum-based chemotherapy. Patients were randomized (2:1) to receive olaparib tablets 300 mg orally twice daily or placebo.
Estimated median investigator-assessed PFS was not reached in the olaparib arm and was 13.8 months in the placebo arm (hazard ratio, 0.30; 95% confidence interval, 0.23-0.41; P less than .0001). Overall survival data are not yet mature.
The most common adverse reactions in women who received olaparib in SOLO-1 were nausea, fatigue, abdominal pain, vomiting, anemia, diarrhea, upper respiratory tract infection/influenza/nasopharyngitis/bronchitis, constipation, dysgeusia, decreased appetite, dizziness, neutropenia, dyspepsia, dyspnea, urinary tract infection, leukopenia, thrombocytopenia, and stomatitis.
The recommended olaparib dose is 300 mg (two 150 mg tablets) taken orally twice daily, with or without food, for a total daily dose of 600 mg, the FDA said in a press statement.
Olaparib is marketed as Lynparza by AstraZeneca Pharmaceuticals.
Beware “The Great Mimicker” that can lurk in the vulva
LAS VEGAS – Officially a type of precancerous lesion is known as vulvar intraepithelial neoplasia (VIN); unofficially, an obstetrician-gynecologist calls it something else: “The Great Mimicker.” That’s because symptoms of VIN can fool physicians into thinking they’re seeing other vulvar conditions. The good news: A biopsy can offer crucial insight and should be performed on any dysplastic or unusual lesion on the vulva.
Amanda Nickles Fader, MD, of Johns Hopkins Hospital in Baltimore, offered this advice and other tips about this type of precancerous vulvar lesion in a presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.
According to Dr. Nickles Fader, vulvar cancer accounts for 5% of all gynecologic malignancies, and it appears most in women aged 65-75 years. However, about 15% of all vulvar cancers appear in women under the age of 40 years. “We’re seeing a greater number of premenopausal women with this condition, probably due to HPV [human papillomavirus],” she said, adding that HPV vaccines are crucial to prevention.
The VIN form of precancerous lesion is most common in premenopausal women (75%) and – like vulvar cancer – is linked to HPV infection, HIV infection, cigarette smoking, and weakened or suppressed immune systems, Dr. Nickles Faber said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
VIN presents with symptoms such as pruritus, altered vulvar appearance at the site of the lesion, palpable abnormality, and perineal pain or burning. About 40% of cases do not show symptoms and are diagnosed by gynecologists at annual visits.
It’s important to biopsy these lesions, she said, because they can mimic other conditions such as vulvar cancer, condyloma acuminatum (genital warts), lichen sclerosus, lichen planus, and condyloma latum (a lesion linked to syphilis).
“Biopsy, biopsy, biopsy,” she urged.
In fact, one form of VIN – differentiated VIN – is associated with dermatologic conditions such as lichen sclerosus, and treatment of these conditions can prevent development of this VIN type.
As for treatment, Dr. Nickles Faber said surgery is the mainstay. About 90% of the time, wide local excision is the “go-to” approach, although the skinning vulvectomy procedure may be appropriate in lesions that are more extensive or multifocal and confluent. “It’s a lot more disfiguring.”
Laser ablation is a “very reasonable” option when cancer has been eliminated as a possibility, she said. It may be appropriate in multifocal or extensive lesions and can have important cosmetic advantages when excision would be inappropriate.
Off-label use of imiquimod 5%, a topical immune response modifier, can be appropriate in multifocal high-grade VINs, but it’s crucial to exclude invasive squamous cell carcinoma. As she noted, imiquimod is Food and Drug Administration–approved for anogenital warts but not for VIN. Beware of toxicity over the long term.
Dr. Nickles Fader reported no relevant financial disclosures.
LAS VEGAS – Officially a type of precancerous lesion is known as vulvar intraepithelial neoplasia (VIN); unofficially, an obstetrician-gynecologist calls it something else: “The Great Mimicker.” That’s because symptoms of VIN can fool physicians into thinking they’re seeing other vulvar conditions. The good news: A biopsy can offer crucial insight and should be performed on any dysplastic or unusual lesion on the vulva.
Amanda Nickles Fader, MD, of Johns Hopkins Hospital in Baltimore, offered this advice and other tips about this type of precancerous vulvar lesion in a presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.
According to Dr. Nickles Fader, vulvar cancer accounts for 5% of all gynecologic malignancies, and it appears most in women aged 65-75 years. However, about 15% of all vulvar cancers appear in women under the age of 40 years. “We’re seeing a greater number of premenopausal women with this condition, probably due to HPV [human papillomavirus],” she said, adding that HPV vaccines are crucial to prevention.
The VIN form of precancerous lesion is most common in premenopausal women (75%) and – like vulvar cancer – is linked to HPV infection, HIV infection, cigarette smoking, and weakened or suppressed immune systems, Dr. Nickles Faber said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
VIN presents with symptoms such as pruritus, altered vulvar appearance at the site of the lesion, palpable abnormality, and perineal pain or burning. About 40% of cases do not show symptoms and are diagnosed by gynecologists at annual visits.
It’s important to biopsy these lesions, she said, because they can mimic other conditions such as vulvar cancer, condyloma acuminatum (genital warts), lichen sclerosus, lichen planus, and condyloma latum (a lesion linked to syphilis).
“Biopsy, biopsy, biopsy,” she urged.
In fact, one form of VIN – differentiated VIN – is associated with dermatologic conditions such as lichen sclerosus, and treatment of these conditions can prevent development of this VIN type.
As for treatment, Dr. Nickles Faber said surgery is the mainstay. About 90% of the time, wide local excision is the “go-to” approach, although the skinning vulvectomy procedure may be appropriate in lesions that are more extensive or multifocal and confluent. “It’s a lot more disfiguring.”
Laser ablation is a “very reasonable” option when cancer has been eliminated as a possibility, she said. It may be appropriate in multifocal or extensive lesions and can have important cosmetic advantages when excision would be inappropriate.
Off-label use of imiquimod 5%, a topical immune response modifier, can be appropriate in multifocal high-grade VINs, but it’s crucial to exclude invasive squamous cell carcinoma. As she noted, imiquimod is Food and Drug Administration–approved for anogenital warts but not for VIN. Beware of toxicity over the long term.
Dr. Nickles Fader reported no relevant financial disclosures.
LAS VEGAS – Officially a type of precancerous lesion is known as vulvar intraepithelial neoplasia (VIN); unofficially, an obstetrician-gynecologist calls it something else: “The Great Mimicker.” That’s because symptoms of VIN can fool physicians into thinking they’re seeing other vulvar conditions. The good news: A biopsy can offer crucial insight and should be performed on any dysplastic or unusual lesion on the vulva.
Amanda Nickles Fader, MD, of Johns Hopkins Hospital in Baltimore, offered this advice and other tips about this type of precancerous vulvar lesion in a presentation at the Pelvic Anatomy and Gynecologic Surgery Symposium.
According to Dr. Nickles Fader, vulvar cancer accounts for 5% of all gynecologic malignancies, and it appears most in women aged 65-75 years. However, about 15% of all vulvar cancers appear in women under the age of 40 years. “We’re seeing a greater number of premenopausal women with this condition, probably due to HPV [human papillomavirus],” she said, adding that HPV vaccines are crucial to prevention.
The VIN form of precancerous lesion is most common in premenopausal women (75%) and – like vulvar cancer – is linked to HPV infection, HIV infection, cigarette smoking, and weakened or suppressed immune systems, Dr. Nickles Faber said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
VIN presents with symptoms such as pruritus, altered vulvar appearance at the site of the lesion, palpable abnormality, and perineal pain or burning. About 40% of cases do not show symptoms and are diagnosed by gynecologists at annual visits.
It’s important to biopsy these lesions, she said, because they can mimic other conditions such as vulvar cancer, condyloma acuminatum (genital warts), lichen sclerosus, lichen planus, and condyloma latum (a lesion linked to syphilis).
“Biopsy, biopsy, biopsy,” she urged.
In fact, one form of VIN – differentiated VIN – is associated with dermatologic conditions such as lichen sclerosus, and treatment of these conditions can prevent development of this VIN type.
As for treatment, Dr. Nickles Faber said surgery is the mainstay. About 90% of the time, wide local excision is the “go-to” approach, although the skinning vulvectomy procedure may be appropriate in lesions that are more extensive or multifocal and confluent. “It’s a lot more disfiguring.”
Laser ablation is a “very reasonable” option when cancer has been eliminated as a possibility, she said. It may be appropriate in multifocal or extensive lesions and can have important cosmetic advantages when excision would be inappropriate.
Off-label use of imiquimod 5%, a topical immune response modifier, can be appropriate in multifocal high-grade VINs, but it’s crucial to exclude invasive squamous cell carcinoma. As she noted, imiquimod is Food and Drug Administration–approved for anogenital warts but not for VIN. Beware of toxicity over the long term.
Dr. Nickles Fader reported no relevant financial disclosures.
EXPERT ANALYSIS FROM PAGS
Low BMP-10 levels correlate with poor ovarian cancer survival
Loss of expression of bone morphogenetic protein-10 (BMP-10) in ovarian cancer cells appears to be a marker for poor prognosis, investigators claim.
Low expression of BMP-10 in ovarian cancer tissues and cell lines significantly correlated with higher-stage disease, high-risk features, and poor prognosis. Conversely, over-expression of BMP-10 was significantly associated with inhibition of ovarian cancer cell proliferation, migration, and invasion, reported Yufeng Jin, PhD, and colleagues from Nantong (China) University.
“Loss of BMP-10 expression might represent a poor prognosis in ovarian cancer patients. Meanwhile, loss of BMP-10 could promote malignant behaviors in ovarian cell lines, suggesting it might be a promising tumor suppressor,” they wrote in Pathology – Research and Practice.
Other members of the BMP family of cytokines and metabolites have recently been implicated in development of esophageal squamous cell cancer, breast cancer, and colorectal cancer, and BMP-10 has been linked to ovarian tumor progression, the investigators noted.
To get a better sense of BMP-10’s potential role as an ovarian cancer suppressor, the investigators first examined eight paired samples of ovarian cancers and adjacent normal tissues, and observed that in most pairs expression of the protein was significantly lower in the cancerous tissues (P less than .01).
Next, they looked at BMP-10 expression in ovarian tissues with varying histological grades; they found that it was overexpressed in normal tissues, but underexpressed in ovarian cancer tissues, especially those from patients with advanced grade disease.
The investigators then looked at the association between BMP-10 expression and clinicopathologic features, using a cutoff of 30% as a mean value for BMP-10 expression in tissues. They found the expression of the protein trended toward correlation with FIGO (International Federation of Gynecology and Obstetrics) stage (P = .08) and correlated significantly with histologic grade (P = .018), lymph node metastasis (P = .004), and peritoneal fluid (P = .032). There were no significant correlations with patient age, histologic subtype, residual tumor size or tumor cells in peritoneal fluid, however.
The authors also found that patients whose tissues had low levels of BMP-10 expression had significantly shorter overall survival (P less than .01), and in multivariate analysis, they saw that expression of the protein was an independent prognostic factor (hazard ratio, 4.834; P = .002).
Turning to in vitro studies, they observed that overexpression of the protein inhibited proliferation of an ovarian cancer cell line (Ovca3), while introduction of an antibody that neutralized BMP-10 allowed proliferation to occur unimpeded.
Finally, they showed that BMP-10 overexpression impaired the wound-healing and invasive properties of Ovca3 cells, while knockdown of the protein’s expression promoted migration and invasion of a different ovarian carcinoma cell line (Skov3).
The investigators acknowledged that their study was limited by small sample sizes, and they noted that they did not investigate potential mechanisms for BMP-10’s effect on ovarian cells.
Nonetheless, they concluded that “BMP-10 should be considered as a promising prognostic marker and a crucial regulator for progression of ovarian cancer.”
The study was supported by the Nantong Health and Family Planning Commission. All authors declared having no conflicts of interest.
SOURCE: Jin Y et al. Pathol Res Pract. 2019 Oct 28. doi: 10.1016/j.prp.2018.10.025.
Loss of expression of bone morphogenetic protein-10 (BMP-10) in ovarian cancer cells appears to be a marker for poor prognosis, investigators claim.
Low expression of BMP-10 in ovarian cancer tissues and cell lines significantly correlated with higher-stage disease, high-risk features, and poor prognosis. Conversely, over-expression of BMP-10 was significantly associated with inhibition of ovarian cancer cell proliferation, migration, and invasion, reported Yufeng Jin, PhD, and colleagues from Nantong (China) University.
“Loss of BMP-10 expression might represent a poor prognosis in ovarian cancer patients. Meanwhile, loss of BMP-10 could promote malignant behaviors in ovarian cell lines, suggesting it might be a promising tumor suppressor,” they wrote in Pathology – Research and Practice.
Other members of the BMP family of cytokines and metabolites have recently been implicated in development of esophageal squamous cell cancer, breast cancer, and colorectal cancer, and BMP-10 has been linked to ovarian tumor progression, the investigators noted.
To get a better sense of BMP-10’s potential role as an ovarian cancer suppressor, the investigators first examined eight paired samples of ovarian cancers and adjacent normal tissues, and observed that in most pairs expression of the protein was significantly lower in the cancerous tissues (P less than .01).
Next, they looked at BMP-10 expression in ovarian tissues with varying histological grades; they found that it was overexpressed in normal tissues, but underexpressed in ovarian cancer tissues, especially those from patients with advanced grade disease.
The investigators then looked at the association between BMP-10 expression and clinicopathologic features, using a cutoff of 30% as a mean value for BMP-10 expression in tissues. They found the expression of the protein trended toward correlation with FIGO (International Federation of Gynecology and Obstetrics) stage (P = .08) and correlated significantly with histologic grade (P = .018), lymph node metastasis (P = .004), and peritoneal fluid (P = .032). There were no significant correlations with patient age, histologic subtype, residual tumor size or tumor cells in peritoneal fluid, however.
The authors also found that patients whose tissues had low levels of BMP-10 expression had significantly shorter overall survival (P less than .01), and in multivariate analysis, they saw that expression of the protein was an independent prognostic factor (hazard ratio, 4.834; P = .002).
Turning to in vitro studies, they observed that overexpression of the protein inhibited proliferation of an ovarian cancer cell line (Ovca3), while introduction of an antibody that neutralized BMP-10 allowed proliferation to occur unimpeded.
Finally, they showed that BMP-10 overexpression impaired the wound-healing and invasive properties of Ovca3 cells, while knockdown of the protein’s expression promoted migration and invasion of a different ovarian carcinoma cell line (Skov3).
The investigators acknowledged that their study was limited by small sample sizes, and they noted that they did not investigate potential mechanisms for BMP-10’s effect on ovarian cells.
Nonetheless, they concluded that “BMP-10 should be considered as a promising prognostic marker and a crucial regulator for progression of ovarian cancer.”
The study was supported by the Nantong Health and Family Planning Commission. All authors declared having no conflicts of interest.
SOURCE: Jin Y et al. Pathol Res Pract. 2019 Oct 28. doi: 10.1016/j.prp.2018.10.025.
Loss of expression of bone morphogenetic protein-10 (BMP-10) in ovarian cancer cells appears to be a marker for poor prognosis, investigators claim.
Low expression of BMP-10 in ovarian cancer tissues and cell lines significantly correlated with higher-stage disease, high-risk features, and poor prognosis. Conversely, over-expression of BMP-10 was significantly associated with inhibition of ovarian cancer cell proliferation, migration, and invasion, reported Yufeng Jin, PhD, and colleagues from Nantong (China) University.
“Loss of BMP-10 expression might represent a poor prognosis in ovarian cancer patients. Meanwhile, loss of BMP-10 could promote malignant behaviors in ovarian cell lines, suggesting it might be a promising tumor suppressor,” they wrote in Pathology – Research and Practice.
Other members of the BMP family of cytokines and metabolites have recently been implicated in development of esophageal squamous cell cancer, breast cancer, and colorectal cancer, and BMP-10 has been linked to ovarian tumor progression, the investigators noted.
To get a better sense of BMP-10’s potential role as an ovarian cancer suppressor, the investigators first examined eight paired samples of ovarian cancers and adjacent normal tissues, and observed that in most pairs expression of the protein was significantly lower in the cancerous tissues (P less than .01).
Next, they looked at BMP-10 expression in ovarian tissues with varying histological grades; they found that it was overexpressed in normal tissues, but underexpressed in ovarian cancer tissues, especially those from patients with advanced grade disease.
The investigators then looked at the association between BMP-10 expression and clinicopathologic features, using a cutoff of 30% as a mean value for BMP-10 expression in tissues. They found the expression of the protein trended toward correlation with FIGO (International Federation of Gynecology and Obstetrics) stage (P = .08) and correlated significantly with histologic grade (P = .018), lymph node metastasis (P = .004), and peritoneal fluid (P = .032). There were no significant correlations with patient age, histologic subtype, residual tumor size or tumor cells in peritoneal fluid, however.
The authors also found that patients whose tissues had low levels of BMP-10 expression had significantly shorter overall survival (P less than .01), and in multivariate analysis, they saw that expression of the protein was an independent prognostic factor (hazard ratio, 4.834; P = .002).
Turning to in vitro studies, they observed that overexpression of the protein inhibited proliferation of an ovarian cancer cell line (Ovca3), while introduction of an antibody that neutralized BMP-10 allowed proliferation to occur unimpeded.
Finally, they showed that BMP-10 overexpression impaired the wound-healing and invasive properties of Ovca3 cells, while knockdown of the protein’s expression promoted migration and invasion of a different ovarian carcinoma cell line (Skov3).
The investigators acknowledged that their study was limited by small sample sizes, and they noted that they did not investigate potential mechanisms for BMP-10’s effect on ovarian cells.
Nonetheless, they concluded that “BMP-10 should be considered as a promising prognostic marker and a crucial regulator for progression of ovarian cancer.”
The study was supported by the Nantong Health and Family Planning Commission. All authors declared having no conflicts of interest.
SOURCE: Jin Y et al. Pathol Res Pract. 2019 Oct 28. doi: 10.1016/j.prp.2018.10.025.
Key clinical point: Expression levels of BMP-10 significantly correlated with ovarian cancer features and patient prognosis.
Major finding: Patients whose tissues had low levels of BMP-10 expression had significantly shorter overall survival (P less than .01),
Study details: Analysis of BMP-10 expression in ovarian cancers, normal tissues, and ovarian cancer cell lines.
Disclosures: The study was supported by the Nantong Health and Family Planning Commission. All authors declared having no conflicts of interest.
Source: Jin Y et al. Pathol Res Pract. 2018 Oct 28. doi: 10.1016/j.prp.2018.10.025.
HPV-16/-18 dramatically increases risk of high-grade CIN in young women
Young women with HPV-16/-18 are significantly more likely to develop high-grade cervical intraepithelial neoplasia (CIN), compared with young women who do not have HPV-16/-18, and therefore require close monitoring, according to a 9-year study of more than 500 women.
Specific strain of HPV had less effect on risk in women aged 30 years or older, compared with younger women, reported lead author Maria Fröberg, MD, PhD, of Karolinska University Hospital and Institute in Stockholm and her colleagues.
“With today’s introduction of HPV primary screening into several organized screening programs and with many triage algorithms available, further research is needed to ensure safe follow-up management and prevent the unnecessary treatment of transient positive HPV findings associated with regressive high-grade CIN,” the investigators wrote in Cancer.
To better understand risk associated with HPV, the investigators drew from a database of 9,464 Swedish women who were cytologically negative for cervical intraepithelial lesions or malignancy (NILM) at baseline during 2005-2007. These baseline-negative women were followed for 9 years; during this time, 96 women developed histologically confirmed, high-grade CIN (CIN2, CIN3, cervical cancer, or adenocarcinoma in situ [AIS]). For each case, five age-matched women were selected who did not develop high-grade CIN to make a control cohort of 480 women.
Approximately half of the cases had CIN2 (45.8%), and half had CIN3 or worse histopathology (CIN3+, 54.2%). HPV-16/-18 was more often associated with CIN3+, compared with CIN2 (Pearson x2, 6.12; P less than .02 [2-sided]). Women with high-grade CIN were significantly more likely to have HPV of any strain, compared with controls (odds ratio, 6.78). Women aged younger than 30 years who had HPV-16/-18 at baseline were far more likely to develop high-grade CIN (OR, 9.44) but showed less impact from other strains of HPV (OR, 2.24). In contrast, women aged 30 years or older showed similar increases in high-grade CIN risk when comparing HPV-16/-18 with other strains (OR, 8.16 vs. 9.04).
“These latter findings suggest that genotyping for HPV-16/-18 might be useful for risk stratification among younger women,” the investigators suggested, noting that “further prospective study on this topic is warranted.”
The study was funded by the Swedish Cancer Foundation, the Stockholm County Council, the Swedish Research Council, and the King Gustaf V Jubilee Fund, and the Karolinska Institute. During the study, one investigator received grants from VALGENT and the 7th Framework Programme of DG Research and Innovation (European Commission).
SOURCE: Fröberg M et al. Cancer. 2018 Dec 10. doi: 10.1002/cncr.31788.
Young women with HPV-16/-18 are significantly more likely to develop high-grade cervical intraepithelial neoplasia (CIN), compared with young women who do not have HPV-16/-18, and therefore require close monitoring, according to a 9-year study of more than 500 women.
Specific strain of HPV had less effect on risk in women aged 30 years or older, compared with younger women, reported lead author Maria Fröberg, MD, PhD, of Karolinska University Hospital and Institute in Stockholm and her colleagues.
“With today’s introduction of HPV primary screening into several organized screening programs and with many triage algorithms available, further research is needed to ensure safe follow-up management and prevent the unnecessary treatment of transient positive HPV findings associated with regressive high-grade CIN,” the investigators wrote in Cancer.
To better understand risk associated with HPV, the investigators drew from a database of 9,464 Swedish women who were cytologically negative for cervical intraepithelial lesions or malignancy (NILM) at baseline during 2005-2007. These baseline-negative women were followed for 9 years; during this time, 96 women developed histologically confirmed, high-grade CIN (CIN2, CIN3, cervical cancer, or adenocarcinoma in situ [AIS]). For each case, five age-matched women were selected who did not develop high-grade CIN to make a control cohort of 480 women.
Approximately half of the cases had CIN2 (45.8%), and half had CIN3 or worse histopathology (CIN3+, 54.2%). HPV-16/-18 was more often associated with CIN3+, compared with CIN2 (Pearson x2, 6.12; P less than .02 [2-sided]). Women with high-grade CIN were significantly more likely to have HPV of any strain, compared with controls (odds ratio, 6.78). Women aged younger than 30 years who had HPV-16/-18 at baseline were far more likely to develop high-grade CIN (OR, 9.44) but showed less impact from other strains of HPV (OR, 2.24). In contrast, women aged 30 years or older showed similar increases in high-grade CIN risk when comparing HPV-16/-18 with other strains (OR, 8.16 vs. 9.04).
“These latter findings suggest that genotyping for HPV-16/-18 might be useful for risk stratification among younger women,” the investigators suggested, noting that “further prospective study on this topic is warranted.”
The study was funded by the Swedish Cancer Foundation, the Stockholm County Council, the Swedish Research Council, and the King Gustaf V Jubilee Fund, and the Karolinska Institute. During the study, one investigator received grants from VALGENT and the 7th Framework Programme of DG Research and Innovation (European Commission).
SOURCE: Fröberg M et al. Cancer. 2018 Dec 10. doi: 10.1002/cncr.31788.
Young women with HPV-16/-18 are significantly more likely to develop high-grade cervical intraepithelial neoplasia (CIN), compared with young women who do not have HPV-16/-18, and therefore require close monitoring, according to a 9-year study of more than 500 women.
Specific strain of HPV had less effect on risk in women aged 30 years or older, compared with younger women, reported lead author Maria Fröberg, MD, PhD, of Karolinska University Hospital and Institute in Stockholm and her colleagues.
“With today’s introduction of HPV primary screening into several organized screening programs and with many triage algorithms available, further research is needed to ensure safe follow-up management and prevent the unnecessary treatment of transient positive HPV findings associated with regressive high-grade CIN,” the investigators wrote in Cancer.
To better understand risk associated with HPV, the investigators drew from a database of 9,464 Swedish women who were cytologically negative for cervical intraepithelial lesions or malignancy (NILM) at baseline during 2005-2007. These baseline-negative women were followed for 9 years; during this time, 96 women developed histologically confirmed, high-grade CIN (CIN2, CIN3, cervical cancer, or adenocarcinoma in situ [AIS]). For each case, five age-matched women were selected who did not develop high-grade CIN to make a control cohort of 480 women.
Approximately half of the cases had CIN2 (45.8%), and half had CIN3 or worse histopathology (CIN3+, 54.2%). HPV-16/-18 was more often associated with CIN3+, compared with CIN2 (Pearson x2, 6.12; P less than .02 [2-sided]). Women with high-grade CIN were significantly more likely to have HPV of any strain, compared with controls (odds ratio, 6.78). Women aged younger than 30 years who had HPV-16/-18 at baseline were far more likely to develop high-grade CIN (OR, 9.44) but showed less impact from other strains of HPV (OR, 2.24). In contrast, women aged 30 years or older showed similar increases in high-grade CIN risk when comparing HPV-16/-18 with other strains (OR, 8.16 vs. 9.04).
“These latter findings suggest that genotyping for HPV-16/-18 might be useful for risk stratification among younger women,” the investigators suggested, noting that “further prospective study on this topic is warranted.”
The study was funded by the Swedish Cancer Foundation, the Stockholm County Council, the Swedish Research Council, and the King Gustaf V Jubilee Fund, and the Karolinska Institute. During the study, one investigator received grants from VALGENT and the 7th Framework Programme of DG Research and Innovation (European Commission).
SOURCE: Fröberg M et al. Cancer. 2018 Dec 10. doi: 10.1002/cncr.31788.
FROM CANCER
Key clinical point: Women with HPV-16/-18 are at significantly higher risk of high-grade cervical intraepithelial neoplasia (CIN), compared with women without HPV-16/-18, and therefore require close monitoring.
Major finding: Women younger than 30 years who test positive for HPV-16/-18 are almost 10 times as likely to develop high-grade CIN, compared with young women negative for HPV-16/-18 (odds ratio, 9.44).
Study details: A nested case-control study involving 96 women who developed high-grade CIN over the 9-year study period, compared with 480 age-matched controls who did not develop cervical lesions.
Disclosures: The study was funded by the Swedish Cancer Foundation, the Stockholm County Council, the Swedish Research Council, and the King Gustaf V Jubilee Fund, and the Karolinska Institute. During the study, one investigator received grants from VALGENT and the 7th Framework Programme of DG Research and Innovation (European Commission).
Source: Fröberg M et al. Cancer. 2018 Dec 10. doi: 10.1002/cncr.31788.
Uterine tissue extraction: An update, with a look at tools and techniques
At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.
Morcellation history
Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?
The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer1). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.2
The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.3
Balancing risks and benefits of MIS
After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.
In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.4
Continue to: Morcellation decisions
Morcellation decisions
Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.
Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).5
An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.
Takeaways
Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:
- There are no comparative data on which technique [of tissue removal] is best.
- Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
- Even with the current generation of tissue bags, leakage is common and puncture is possible.
If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.
Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.
- Wright JD, Tergas AI, Burke WM, et al. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA. Published online July 22, 2014. Accessed December 10, 2018.
- US Food and Drug Administration. Laparoscopic uterine power morcellation in hysterectomy and myomectomy: FDA safety communication. November 24, 2014. http://wayback.archive-it.org/7993/20170722215727/https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm424443.htm. Updated June 6, 2017. Accessed December 10, 2018.
- Siedhoff MT, Wheeler SB, Rutstein SE, et al. Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis. Am J Obstet Gynecol. 2015;212:591.e1–e8.
- FDA In Brief: FDA releases new findings on the risks of spreading hidden uterine cancer through the use of laparoscopic power morcellators. https://www.fda.gov/newsevents/newsroom/fdainbrief/ucm589137.htm. Updated December 14, 2017. Accessed December 10, 2018.
- Ramos A, Fader AN, Roche KL. Surgical cytoreduction for disseminated benign disease after open power uterine morcellation. Obstet Gynecol. 2015;125:99-102.
At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.
Morcellation history
Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?
The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer1). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.2
The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.3
Balancing risks and benefits of MIS
After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.
In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.4
Continue to: Morcellation decisions
Morcellation decisions
Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.
Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).5
An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.
Takeaways
Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:
- There are no comparative data on which technique [of tissue removal] is best.
- Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
- Even with the current generation of tissue bags, leakage is common and puncture is possible.
If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.
Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.
At the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada, Tommaso Falcone, MD, Chief of Staff, Chief Academic Officer, and Medical Director at Cleveland Clinic London, England, addressed the status of tissue morcellation in hysterectomy and myomectomy after several years’ controversy—noting that the specialty’s professional societies all support use of the technique, with precautions and in selected patients.
Morcellation history
Should electromechanical (‘power’) morcellation of tissue be a tool for performing minimally invasive hysterectomy and myomectomy? If so, what are the risks and benefits of using this tool, first approved by the US Food and Drug Administration (FDA) in 1995?
The matter came under intense scrutiny and debate in 2014 as concerns rose about the potential of power morcellation to disseminate intraperitoneal malignancy in women with occult cancer (an estimated 1 in 370 women who undergo power morcellation during a minimally invasive hysterectomy have uterine cancer1). Early that year, the FDA moved to strongly discourage use of power morcellators for removing uterine fibroids.2
The aftermath, however, was that there were problems with the FDA’s [2014] statement, Dr. Falcone pointed out. In a study by Siedhoff and colleagues of a hypothetical cohort of 100,000 women with fibroids, for example, an abdominal approach resulted in more hysterectomy-related deaths and surgery-related complications than did a laparoscopic procedure with morcellation.3
Balancing risks and benefits of MIS
After continuing study of the risks presented by morcellation, the question today is: How do we balance preventing dissemination of cancer against diminishing the significant benefits of minimally invasive surgery, as surgical technique has been modified to avoid morcellation—including, Dr. Falcone said, by increased use of mini lap (i.e., extending the laparoscopy incision) tissue extraction, decreased use of supracervical hysterectomy, and a move to open approaches.
In fact, Dr. Falcone noted, power morcellation is banned in many institutions, having been replaced by scalpel, extraperitoneal, or in-bag morcellation. Last year, after further analysis, the FDA reiterated its recommendation against use of power morcellators to remove fibroids in most women.4
Continue to: Morcellation decisions
Morcellation decisions
Dr. Falcone pointed out that, at the Cleveland Clinic, morcellation is not performed in postmenopausal women, and for several other contraindications, including a history of >2 years of tamoxifen therapy; history of pelvic radiation; history of childhood retinoblastoma; personal history of hereditary leiomyomatosis or renal cell carcinoma; and the presence of a cancer-positive tissue specimen. Morcellation is not performed unless endometrial adenocarcinoma has been ruled out. The decision-making process when electing to use tissue extraction includes whether to use contained or noncontained morcellation; whether to favor knife excision over power morcellation; and, when using a mini lap approach, whether to proceed via the umbilicus or suprapubically.
Complications of morcellation include direct injury by the morcellator; dissemination, as noted, of tissue; ‘upstaging’ of uterine sarcoma, with a worsening prognosis; seeding of parasitic fibroids; and reoperation with laparotomy and extensive multi-organ resection to clear disease (3 patients in a published report).5
An important advancement in the use of morcellation in minimally invasive hysterectomy or myomectomy has been the development of contained systems for morcellating—generally a plastic specimen bag, sometimes pulled through the port and insufflated. Dr. Falcone’s presentation included video presentations of this important, and still evolving, technology. Whether these contained systems improve survival, and whether using them in a vaginal approach makes any difference, remain uncertain, however. Furthermore, some spillage from bags is inevitable—although how much spillage is clinically significant is open to question.
Takeaways
Dr. Falcone concluded with key points to guide the surgeon’s decision on whether to proceed with morcellation:
- There are no comparative data on which technique [of tissue removal] is best.
- Tissue spill will occur in uncontained morcellation—this is intrinsic to the device.
- Even with the current generation of tissue bags, leakage is common and puncture is possible.
If you choose to continue to use power morcellation, your decision is supported by the fact that all the professional societies still support it, Dr. Falcone noted. Furthermore, he pointed out that it is important to look to the standard of care in your community regarding risks and benefits before proceeding.
Last, the advantages and risks of morcellation in hysterectomy and myomectomy should be part of an in-depth discussion between patient and surgeon prior to the procedure. And you must, Dr. Falcone emphasized, obtain specific informed consent.
- Wright JD, Tergas AI, Burke WM, et al. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA. Published online July 22, 2014. Accessed December 10, 2018.
- US Food and Drug Administration. Laparoscopic uterine power morcellation in hysterectomy and myomectomy: FDA safety communication. November 24, 2014. http://wayback.archive-it.org/7993/20170722215727/https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm424443.htm. Updated June 6, 2017. Accessed December 10, 2018.
- Siedhoff MT, Wheeler SB, Rutstein SE, et al. Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis. Am J Obstet Gynecol. 2015;212:591.e1–e8.
- FDA In Brief: FDA releases new findings on the risks of spreading hidden uterine cancer through the use of laparoscopic power morcellators. https://www.fda.gov/newsevents/newsroom/fdainbrief/ucm589137.htm. Updated December 14, 2017. Accessed December 10, 2018.
- Ramos A, Fader AN, Roche KL. Surgical cytoreduction for disseminated benign disease after open power uterine morcellation. Obstet Gynecol. 2015;125:99-102.
- Wright JD, Tergas AI, Burke WM, et al. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA. Published online July 22, 2014. Accessed December 10, 2018.
- US Food and Drug Administration. Laparoscopic uterine power morcellation in hysterectomy and myomectomy: FDA safety communication. November 24, 2014. http://wayback.archive-it.org/7993/20170722215727/https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm424443.htm. Updated June 6, 2017. Accessed December 10, 2018.
- Siedhoff MT, Wheeler SB, Rutstein SE, et al. Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis. Am J Obstet Gynecol. 2015;212:591.e1–e8.
- FDA In Brief: FDA releases new findings on the risks of spreading hidden uterine cancer through the use of laparoscopic power morcellators. https://www.fda.gov/newsevents/newsroom/fdainbrief/ucm589137.htm. Updated December 14, 2017. Accessed December 10, 2018.
- Ramos A, Fader AN, Roche KL. Surgical cytoreduction for disseminated benign disease after open power uterine morcellation. Obstet Gynecol. 2015;125:99-102.
When is it appropriate to remove ovaries in hysterectomy?
LAS VEGAS – The removal of both ovaries during hysterectomy – bilateral salpingo-oophorectomy (BSO) – has declined sharply in popularity as physicians have become more aware of its risks.
Still, “we’re still seeing a relatively high rate of inappropriate BSO,” Amanda Nickles Fader, MD, said, despite “the many benefits of ovarian conservation. Strong consideration should be made for maintaining normal ovaries in premenopausal women who are not at higher genetic risk of ovarian cancer.”
Dr. Nickles Fader, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, who spoke at the Pelvic Anatomy and Gynecologic Surgery Symposium, urged gynecologists to understand the data about ovarian conservation in hysterectomy and carefully counsel patients.
“We can counsel patients with 100% certainty that BSO absolutely reduces ovarian and fallopian tube cancer rates. That’s a given,” she said. “Women get very excited about that, but you’ve got to be careful to counsel them about the flip side: The overall benefit may not be there when you consider the other morbidity and mortality that may occur because of this removal.”
As she noted, multiple retrospective, prospective, and observational studies have linked ovary removal to a variety of heightened risks, especially on the cardiac front. She highlighted a 2009 study of nearly 30,000 nurses who’d undergone hysterectomy for benign disease, about which the authors wrote that, “compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.” No age group gained a survival benefit from oophorectomy (Obstet Gynecol. 2009 May;113[5]:1027-37 ).
Meanwhile, over the past decade, the “pendulum has swung” toward ovary conservation, at least in premenopausal women, Dr. Nickles Fader said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
A 2016 analysis of health statistics in five U.S. Eastern and Midwestern states found that, rates of hospital-based, hysterectomy-alone procedures grew by 15% from 2005 to 2013, while rates of oophorectomy alone and hysterectomy/oophorectomy combination procedures declined by 12% and 29%, respectively.
Still, Dr. Nickles Fader said, as many as 60% of hysterectomies are still performed in conjunction with oophorectomy.
Ovary removal, of course, can be appropriate when patients are at risk of ovarian cancer. Hereditary ovarian cancer accounts for up to 25% of epithelial ovarian cancer, she said, and research suggests that risk-reducing surgery is an effective preventative approach when high-penetrance genes are present. However, the value of the surgery is less clear in regard to moderate-penetrance genes.
Dr. Nickles Fader pointed to guidelines from the National Comprehensive Cancer Network that specify genes and syndromes that should trigger risk-reducing salpingo-oophorectomy, hysterectomy, or hysterectomy and risk-reducing salpingo-oophorectomy after childbirth.
Researchers are exploring salpingectomy – fallopian tube removal – as a possible replacement for oophorectomy. Dr. Nickles Fader highlighted a small pilot study published in 2018 that reported “BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.”
Moving forward, she said, research will provide more insight into preventative options such as removing fallopian tubes alone instead of ovaries. “We’re starting to learn, and will probably know in the next 10-15 years, whether oophorectomy is necessary for all high-risk and moderate-risk women or if we can get away with removing their tubes and giving them the maximal health benefits of ovarian conservation.”
Dr. Nickles Fader reported consulting for Ethicon Endosurgery.
LAS VEGAS – The removal of both ovaries during hysterectomy – bilateral salpingo-oophorectomy (BSO) – has declined sharply in popularity as physicians have become more aware of its risks.
Still, “we’re still seeing a relatively high rate of inappropriate BSO,” Amanda Nickles Fader, MD, said, despite “the many benefits of ovarian conservation. Strong consideration should be made for maintaining normal ovaries in premenopausal women who are not at higher genetic risk of ovarian cancer.”
Dr. Nickles Fader, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, who spoke at the Pelvic Anatomy and Gynecologic Surgery Symposium, urged gynecologists to understand the data about ovarian conservation in hysterectomy and carefully counsel patients.
“We can counsel patients with 100% certainty that BSO absolutely reduces ovarian and fallopian tube cancer rates. That’s a given,” she said. “Women get very excited about that, but you’ve got to be careful to counsel them about the flip side: The overall benefit may not be there when you consider the other morbidity and mortality that may occur because of this removal.”
As she noted, multiple retrospective, prospective, and observational studies have linked ovary removal to a variety of heightened risks, especially on the cardiac front. She highlighted a 2009 study of nearly 30,000 nurses who’d undergone hysterectomy for benign disease, about which the authors wrote that, “compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.” No age group gained a survival benefit from oophorectomy (Obstet Gynecol. 2009 May;113[5]:1027-37 ).
Meanwhile, over the past decade, the “pendulum has swung” toward ovary conservation, at least in premenopausal women, Dr. Nickles Fader said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
A 2016 analysis of health statistics in five U.S. Eastern and Midwestern states found that, rates of hospital-based, hysterectomy-alone procedures grew by 15% from 2005 to 2013, while rates of oophorectomy alone and hysterectomy/oophorectomy combination procedures declined by 12% and 29%, respectively.
Still, Dr. Nickles Fader said, as many as 60% of hysterectomies are still performed in conjunction with oophorectomy.
Ovary removal, of course, can be appropriate when patients are at risk of ovarian cancer. Hereditary ovarian cancer accounts for up to 25% of epithelial ovarian cancer, she said, and research suggests that risk-reducing surgery is an effective preventative approach when high-penetrance genes are present. However, the value of the surgery is less clear in regard to moderate-penetrance genes.
Dr. Nickles Fader pointed to guidelines from the National Comprehensive Cancer Network that specify genes and syndromes that should trigger risk-reducing salpingo-oophorectomy, hysterectomy, or hysterectomy and risk-reducing salpingo-oophorectomy after childbirth.
Researchers are exploring salpingectomy – fallopian tube removal – as a possible replacement for oophorectomy. Dr. Nickles Fader highlighted a small pilot study published in 2018 that reported “BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.”
Moving forward, she said, research will provide more insight into preventative options such as removing fallopian tubes alone instead of ovaries. “We’re starting to learn, and will probably know in the next 10-15 years, whether oophorectomy is necessary for all high-risk and moderate-risk women or if we can get away with removing their tubes and giving them the maximal health benefits of ovarian conservation.”
Dr. Nickles Fader reported consulting for Ethicon Endosurgery.
LAS VEGAS – The removal of both ovaries during hysterectomy – bilateral salpingo-oophorectomy (BSO) – has declined sharply in popularity as physicians have become more aware of its risks.
Still, “we’re still seeing a relatively high rate of inappropriate BSO,” Amanda Nickles Fader, MD, said, despite “the many benefits of ovarian conservation. Strong consideration should be made for maintaining normal ovaries in premenopausal women who are not at higher genetic risk of ovarian cancer.”
Dr. Nickles Fader, director of the Kelly gynecologic oncology service and the director of the center for rare gynecologic cancers at Johns Hopkins Hospital, Baltimore, who spoke at the Pelvic Anatomy and Gynecologic Surgery Symposium, urged gynecologists to understand the data about ovarian conservation in hysterectomy and carefully counsel patients.
“We can counsel patients with 100% certainty that BSO absolutely reduces ovarian and fallopian tube cancer rates. That’s a given,” she said. “Women get very excited about that, but you’ve got to be careful to counsel them about the flip side: The overall benefit may not be there when you consider the other morbidity and mortality that may occur because of this removal.”
As she noted, multiple retrospective, prospective, and observational studies have linked ovary removal to a variety of heightened risks, especially on the cardiac front. She highlighted a 2009 study of nearly 30,000 nurses who’d undergone hysterectomy for benign disease, about which the authors wrote that, “compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.” No age group gained a survival benefit from oophorectomy (Obstet Gynecol. 2009 May;113[5]:1027-37 ).
Meanwhile, over the past decade, the “pendulum has swung” toward ovary conservation, at least in premenopausal women, Dr. Nickles Fader said at the meeting jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
A 2016 analysis of health statistics in five U.S. Eastern and Midwestern states found that, rates of hospital-based, hysterectomy-alone procedures grew by 15% from 2005 to 2013, while rates of oophorectomy alone and hysterectomy/oophorectomy combination procedures declined by 12% and 29%, respectively.
Still, Dr. Nickles Fader said, as many as 60% of hysterectomies are still performed in conjunction with oophorectomy.
Ovary removal, of course, can be appropriate when patients are at risk of ovarian cancer. Hereditary ovarian cancer accounts for up to 25% of epithelial ovarian cancer, she said, and research suggests that risk-reducing surgery is an effective preventative approach when high-penetrance genes are present. However, the value of the surgery is less clear in regard to moderate-penetrance genes.
Dr. Nickles Fader pointed to guidelines from the National Comprehensive Cancer Network that specify genes and syndromes that should trigger risk-reducing salpingo-oophorectomy, hysterectomy, or hysterectomy and risk-reducing salpingo-oophorectomy after childbirth.
Researchers are exploring salpingectomy – fallopian tube removal – as a possible replacement for oophorectomy. Dr. Nickles Fader highlighted a small pilot study published in 2018 that reported “BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.”
Moving forward, she said, research will provide more insight into preventative options such as removing fallopian tubes alone instead of ovaries. “We’re starting to learn, and will probably know in the next 10-15 years, whether oophorectomy is necessary for all high-risk and moderate-risk women or if we can get away with removing their tubes and giving them the maximal health benefits of ovarian conservation.”
Dr. Nickles Fader reported consulting for Ethicon Endosurgery.
EXPERT ANALYSIS FROM PAGS
Uterine cancer incidence and mortality on the rise in the U.S.
Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.
Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.
In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.
Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.
Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.
The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.
Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.
“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.
Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.
“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vaginal bleeding should be evaluated promptly by a health care provider,” they wrote.
No conflicts of interest were reported.
SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.
Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.
In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.
Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.
Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.
The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.
Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.
“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.
Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.
“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vaginal bleeding should be evaluated promptly by a health care provider,” they wrote.
No conflicts of interest were reported.
SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
Uterine cancer incidence and mortality in the United States increased significantly from 1999 to 2015, with the greatest increases among nonwhite women, according to data published in the Morbidity and Mortality Weekly Report.
Uterine cancer is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among women in the United States, wrote S. Jane Henley and her colleagues from the division of cancer prevention and control at the National Center for Chronic Disease Prevention and Health Promotion. Its incidence is thought to be on the rise because of the increasing prevalence of overweight and obesity.
In this report, researchers analyzed data from population-based cancer registries to find new cases of invasive uterine cancer from 1999 to 2015.
Over that period, incidence rates of uterine cancer increased around 0.7% per year on average, with an overall 12% increase. However, among American Indian and Alaskan Native women, the incidence rate during that time increased by 53%, among black women it increased by 46%, among Asian/Pacific Island women the incidence rate increased by 38%, and among Hispanic women it increased by 32%.
Uterine cancer death rates also increased by 21% from 1999 to 2015, representing approximately a 1.1% average increase per year. Again, the greatest increases were seen in American Indian and Alaskan Native women (52%), Hispanic women (33%), and black women (29%). Death rates increased by 18% among white women but were stable among Asian/Pacific Island women.
The most common type of uterine cancer was the endometrioid carcinomas, which accounted for 68% of uterine cancers overall. However black women had a higher percentage of other carcinomas, carcinosarcomas, and sarcomas, compared with women from other ethnic groups.
Two-thirds of cancer overall were diagnosed at a localized stage, but this was less common in black women than women of other ethnicities, while the proportion of cancers diagnosed at distant stage was higher among black women.
“This report found that black women were more likely to receive a diagnosis at distant stage and with more aggressive histologic types than were other women, which might in part account for the higher death rate among black women,” the authors wrote.
Despite the increasing incidence and mortality, the authors wrote that population-based screening tests are not recommended for uterine cancer, partly because around 90% of women with uterine cancer report abnormal vaginal bleeding.
“Uterine cancer outcomes could be improved by increasing awareness among women that abnormal vaginal bleeding should be evaluated promptly by a health care provider,” they wrote.
No conflicts of interest were reported.
SOURCE: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
FROM MMWR
Key clinical point: Uterine cancer incidence and mortality rose from 1999 to 2015 in the United States.
Major finding: The incidence of uterine cancer in the United States increased 12% from 1999 to 2015.
Study details: An analysis of cancer registry data.
Disclosures: No conflicts of interest were reported.
Source: Henley SJ et al. MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67:1333-8.
Maternal health benefits of breastfeeding
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital, Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School, Boston
_
Dr. Barbieri reports no financial relationships relevant to this article.
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital, Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School, Boston
_
Dr. Barbieri reports no financial relationships relevant to this article.
Editor in Chief, OBG Management
Chair, Obstetrics and Gynecology
Brigham and Women’s Hospital, Boston, Massachusetts
Kate Macy Ladd Professor of Obstetrics,
Gynecology and Reproductive Biology
Harvard Medical School, Boston
_
Dr. Barbieri reports no financial relationships relevant to this article.
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
Does low-dose aspirin decrease a woman’s risk of ovarian cancer?
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
