This matched historical cohort study evaluated the association between oral contraceptive (OC) use and levonorgestrel-releasing intrauterine device (LNG-IUD) use and the risks of breast and ovarian cancer in 1,677 BRCA1/2 pathogenic variant carriers (BRCA1 n=990; BRCA2 n=687) from Clalit Health Services in Israel, followed from age 18 through December 2024.
In BRCA2 carriers, OC use was associated with reduced breast cancer risk (HR 0.80, 95% CI 0.65–0.99) and reduced ovarian cancer risk (HR 0.57, 95% CI 0.35–0.94), with the strongest ovarian protection in long-term users >5 years (HR 0.13, 95% CI 0.02–0.92). In BRCA1 carriers, OC use was not significantly associated with breast cancer risk (HR 0.90, 95% CI 0.77–1.05) or ovarian cancer risk (HR 0.70, 95% CI 0.48–1.03, p=0.071). LNG-IUD use was not associated with breast or ovarian cancer risk in either gene group.
- Retrospective design with potential selection and information bias; OC formulation details, adherence, and contraindications were unavailable. - No consistent dose-response relationship seen for the BRCA2 breast cancer finding, limiting causal interpretation. - Small number of LNG-IUD users limits power to detect an effect; HRT was not modeled as a time-dependent covariate, risking residual confounding.
For women with a BRCA2 pathogenic variant who are not yet ready for risk-reducing oophorectomy, OC use — especially long-term — may offer meaningful ovarian cancer protection and should be discussed as part of counseling. LNG-IUD does not appear to increase breast or ovarian cancer risk in BRCA1/2 carriers, but its protective effect against ovarian cancer also appears absent.
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