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• W3157869330 abstract "Abstract Purpose To determine whether germline BRCA pathogenic variants (g BRCA ) are associated with decreased ovarian reserve. Materials and Methods An individual patient-data meta-analysis was performed using 5 datasets on 828 evaluable women who were tested for g BRCA . Of those, 250 carried g BRCA while 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-mullerian hormone (AMH) levels in affected women were drawn before pre-systemic therapy. Results Mean ages of women with vs. without g BRCA1/2 (34.1± 4.9 vs. 34.3± 4.8 years; p=0.48), and with g BRCA1 vs g BRCA2 (33.7± 4.9 vs. 34.6± 4.8 years; p=0.16) were similar. After the adjustments, women with g BRCA1/2 had significantly lower AMH levels compared to controls (23% lower; 95% CI: 4-38%, p=0.02). When the adjusted analysis was limited to affected women (157 with g BRCA vs. 524 without, after exclusions), the difference persisted (25% lower; CI: 9-38%, p=0.003). The serum AMH levels were lower in women with g BRCA 1 (33% lower; CI: 12-49%, p=0.004) but not g BRCA 2 compared to controls (7% lower; CI: 31% lower to 26% higher, p=0.64). Conclusions Young women with g BRCA pathogenic variants, particularly of those affected and with g BRCA1 , have lower serum AMH levels compared to controls. They may need to be preferentially counselled about the possibility of shortened reproductive lifespan due to diminished ovarian reserve. Context Key objective DNA repair deficiency is emerging as a joint mechanism for breast cancer and reproductive aging. Recent studies showed that ovarian reserve maybe lower in women with BRCA pathogenic variants (g BRCA) due to DNA repair deficiency. However, clinical studies using the most sensitive serum ovarian reserve marker Anti-Mullerian-Hormone (AMH) provided mixed results. Given the heterogeneity of the data from clinical studies, we performed an individual patient data (IPD) meta-analysis to determine if g BRCA are associated with lower ovarian reserve. Knowledge generated g BRCA are associated with diminished ovarian reserve, as determined by serum AMH and this association is restricted to g BRCA1 . This finding is firmer for affected women as this IPD meta-analysis predominantly studied those with breast cancer. Relevance Women with g BRCA may have shortened reproductive life span due to diminished ovarian reserve and should be proactively counseled for fertility preservation especially if faced with chemotherapy or delaying childbearing." @default.
• W3157869330 created "2021-05-10" @default.
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• W3157869330 date "2021-02-16" @default.
• W3157869330 modified "2023-10-16" @default.
• W3157869330 title "Association of Germline BRCA Pathogenic Variants with Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data" @default.
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• W3157869330 doi "https://doi.org/10.1101/2021.02.13.21251672" @default.
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