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2022-RA-645-ESGO Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers, a systematic review and meta-analysis
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  1. Majke van Bommel1,
  2. Joanna IntHout2,
  3. Guus Veldmate3,
  4. Marleen Kets2,
  5. Joanne de Hullu2,
  6. Anne van Altena2 and
  7. Marline Harmsen2
  1. 1Obstetrics and Gynecology, Radboud university medical center, Nijmegen, Netherlands
  2. 2Radboud university medical center, Nijmegen, Netherlands
  3. 3Gelderse Vallei Hospital, Ede, Netherlands

Abstract

Introduction/Background BRCA1/2 pathogenic variant (PV) carriers have a high risk of breast and ovarian cancer. Contraceptives impact these risks in the general population. Among BRCA1/2-PV carriers, sufficient data and clear recommendations regarding contraceptives are lacking. We investigated how contraceptives modify breast and ovarian cancer risk in BRCA1/2-PV carriers.

Methodology We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used contraception (any kind) versus BRCA1/2-PV carriers who have not. A systematic search identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and per contraceptive.

Abstract 2022-RA-645-ESGO Figure 1

Results Meta-analysis of 11 studies, including 25,857 women, reveals that breast cancer risk may be increased by the oral contraceptive pill, depending on outcome measure: hazard ratio 1.43 (95% confidence interval (CI) 1.25–1.63) and odds ratio 1.06 (95% CI 0.90–1.25), and the risk remains increased after cessation of use. Meta-analysis of 10 studies with 21,425 women shows that ovarian cancer risk is decreased among oral contraceptive pill users: HR 0.62 (95% CI 0.52; 0.74) and OR 0.49 (95% CI 0.38; 0.63) and the protective effect vanishes after cessation of use. Tubal ligation protects against ovarian cancer (HR 0.44 (95% CI 0.26; 0.74) and OR 0.74 (0.53; 1.03)). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers.

Conclusion The oral contraceptive pill potentially increases breast cancer risk, while ovarian cancer risk decreases by both the oral contraceptive pill and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers about contraceptives should be a personalized weighing of genetic and non-genetic factors and patients’ preferences.

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