Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data. Issue 18 (20th June 2021)

• Record Type: Journal Article
• Authors: Turan, Volkan; Lambertini, Matteo; Lee, Dong-Yun; Wang, Erica; Clatot, Florian; Karlan, Beth Y.; Demeestere, Isabelle; Bang, Heejung; Oktay, Kutluk
• Is Part Of: Journal of clinical oncology. Volume 39:Issue 18(2021)
• Page Start: 2016
• Page End: 2024
• Publication Date: 2021-06-20
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.20.02880
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: To determine whether germline BRCA (g BRCA ) pathogenic variants are associated with decreased ovarian reserve. MATERIALS AND METHODS: An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for g BRCA . Of those, 250 carried g BRCA, whereas 578 had tested negative and served as controls. Of the women with g BRCA, four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy. RESULTS: The mean age of women with versus without g BRCA1/2 (34.1 ± 4.9 v 34.3 ± 4.8 years; P = .48) and with g BRCA1 versus g BRCA2 (33.7 ± 4.9 v 34.6 ± 4.8 years; P = .16) was similar. After the adjustments, women with g BRCA1/2 had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; P = .02). When the adjusted analysis was limited to affected women (157 with g BRCA v 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; P = .003). The serum AMH levels were lower in women with g BRCA1 (33% lower; 95% CI, 12 to 49; P = .004) but not g BRCA2 compared with controls (7% lower; 95% CI, 31% lower to 26% higher; P = .64). CONCLUSION: Young women with g BRCA pathogenic variants, particularly those affected and with g 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.