BRCA1 Germline Mutation Associated With Reduced Ovarian Reserve
Study results show that women who carry a BRCA1 mutation have a shorter reproductive lifespan than noncarriers.
Women with a germline mutation in BRCA1 have reduced ovarian reserve, suggesting that older women with this mutation should not delay pregnancy, a study in Human Reproduction reported.1
This study found levels of anti-Müllerian hormone (AMH)—a biomarker of ovarian reserve and, therefore, reproductive lifespan—to be an average of 25% lower in BRCA1 carriers than in noncarriers. Although the DNA repair enzymes encoded by both BRCA1 and BRCA2 have been implicated in reproductive aging, this association was not observed for the BRCA2 mutation.
“Our study suggests that, while having a BRCA1 mutation might impact fertility in late reproductive life (ie, late 30s and early 40s), it is unlikely to have an important clinical impact in younger mutation carriers,” Kelly-Anne Phillips, MBBS(Hons), MD, a consultant medical oncologist at the Peter MacCallum Cancer Centre in Australia, told Cancer Therapy Advisor.
BRCA1 and BRCA2 mutations raise the risk of cancers in the breast, ovaries, fallopian tubes, and peritoneum, and this risk increases with age. Women who are aware of their mutation status typically try to conceive at a younger age, as premenopausal bilateral salpingo-oophorectomy is recommended to minimize their cancer risk.
“All women should have their breast cancer risk assessed and appropriately managed according to evidence-based guidelines,” Dr Phillips said. “In addition, women with a strong family history of breast and/or ovarian cancer should consider genetic testing for mutations in the BRCA1 and BRCA2 genes, after a comprehensive discussion with a genetic expert about the potential risks and benefits.”
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The cross-sectional study examined AMH concentrations in 693 women ages 25 to 45 years enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer cohort study from August 19, 1997, to September 18, 2012.
Between November 2014 and January 2015, researchers measured AMH on stored plasma samples using an electrochemiluminescence immunoassay platform. Participants “had no personal history of cancer, retained both ovaries, and were not pregnant or breastfeeding at the time of plasma storage,” Dr Phillips and colleagues wrote.