In a study reported in the Journal of Clinical Oncology, Turan et al found the presence of germline BRCA pathogenic variants was associated with diminished ovarian reserve in young women, particularly in those diagnosed with breast cancer and those with BRCA1 variants.
The individual patient meta-analysis involved five datasets including 828 women (824 eligible for final analysis) from five centers who were tested for germline BRCA. Of the 828 women, 250 (246 eligible) carried germline BRCA and 578 tested negative for germline BRCA (controls). Of the 246 eligible women with germline BRCA, 153 (62.2%) carried germline BRCA1 and 93 (37.8%) carried germline BRCA2.
Data were adjusted for center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Ovarian reserve was measured by serum anti-Müllerian hormone (AMH) levels, with levels in women affected by breast cancer determined before initiation of chemotherapy.
Young women with germline BRCA pathogenic variants, particularly those affected with breast cancer and with germline BRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.— Turan et al
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There was no significant difference in mean age of women with vs without germline BRCA1/2 (34.1 vs 34.3 years, P = .48) or with germline BRCA1 vs germline BRCA2 (33.7 vs 34.6 years, P = .16). In adjusted analysis, women with germline BRCA1/2 had significantly lower mean AMH levels vs controls (23% lower, 95% confidence interval [CI] = 4%–38% lower, P = .02).
In analysis among 157 women with germline BRCA vs 524 without germline BRCA affected by breast cancer, germline BRCA was associated with significantly lower AMH levels (25% lower, 95% CI = 9%–38% lower, P = .003). Compared with controls, AMH levels were significantly lower among women with germline BRCA1 (33% lower, 95% CI = 12%–49% lower, P = .004) but not among those with germline BRCA2 (7% lower, 95% CI = 31% lower to 26% higher, P = .64).
The investigators concluded, “Young women with germline BRCA pathogenic variants, particularly those affected with breast cancer and with germline BRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.”
Kutluk Oktay, MD, PhD, of the Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.