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

Capsule:
In a cohort of 1,073 BRCA mutation carriers, fertility treatments were not found to be risk modifiers for invasive epithelial ovarian cancer.

Authors:
Tamar Perri, M.D., Dror Lifshitz, M.D., Siegal Sadetzki, M.D., M.P.H., Bernice Oberman, M.Sc., Dror Meirow, M.D., Gilad Ben-Baruch, M.D., Eitan Friedman, M.D., Ph.D., Jacob Korach, M.D.

Volume 103, Issue 5, Pages 1305-1312

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.

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