Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers

Abstract

Objective: To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC).

Design: Historical cohort study.

Setting: Tertiary university-affiliated medical center and the National Cancer Registry.

Patient(s): A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility.

Intervention(s): None.

Main outcome measure(s): Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables.

Result(s): In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis.

Conclusion(s): According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.

Keywords: BRCA mutations; cancer risk; fertility treatment; ovarian cancer.