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Oral Contraceptive Use in BRCA1 and BRCA2 Mutation Carriers: Absolute Cancer Risks and Benefits

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Antoniou, antonis 


Background: To help BRCA1/2 mutation carriers make informed decisions regarding use of combined-type oral contraceptive preparation (COCP), absolute risk-benefit estimates are needed for COCP-associated cancer. Methods: For a hypothetical cohort of 10,000 women, we calculated the increased or decreased cumulative incidence of COCP-associated (breast/ovarian/endometrial) cancer, examining 18 scenarios with differences in duration and timing of COCP use, uptake of prophylactic surgeries and menopausal hormone therapy. Results: COCP use initially increased breast cancer risk, and decreased ovarian/endometrial cancer risk long-term. For 10,000 BRCA1 mutation carriers ten years of COCP use from age 20-30 years resulted in 66 additional COCP-associated cancer cases by the age of 35 years, on top of 625 cases expected for never users. By the age of 70 years such COCP use resulted in 907 fewer cancer cases than the expected 9,093 cases in never users. Triple-negative breast cancer estimates resulted in 196 additional COCP-associated cases by age 40 years, on top of 1,454 expected. For 10,000 BRCA2 mutation carriers using COCP from age 20-30 years, 80 excess cancer cases were estimated by age 40 years on top of 651 expected cases; by the age of 70 years we calculated 382 fewer cases compared to the 6,156 cases expected. The long-term benefit of COCP use diminished after risk-reducing bilateral salpingo-oophorectomy (RRSO) followed by menopausal hormone therapy use. Conclusion: While COCP use in BRCA1 and BRCA2 mutation carriers initially increases breast/ovarian/endometrial cancer risk, it strongly decreases lifetime cancer risk. RRSO and menopausal hormone therapy use appear to counteract the long-term COCP-benefit.



Adult, Aged, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Contraceptives, Oral, Combined, Endometrial Neoplasms, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Heterozygote, Humans, Mutation, Ovarian Neoplasms, Ovariectomy, Risk Assessment, Young Adult

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Journal of the National Cancer Institute

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Oxford University Press (OUP)
Pink-Ribbon/Dutch-Cancer-Society (2014-187.WO76) and Transcan-JT (2012/Cancer-12-054)

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2023-12-22 10:24:58
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