Fertility treatments and breast cancer risk in Jewish Israeli BRCA mutation carriers

In a large historical cohort study of fertility treatments for BRCA1/2 mutation carriers, clomiphene-citrate, gonadotropins, IVF or combined treatments were not associated with a discernible increase in breast cancer risk.

VOLUME 116, ISSUE 2, P538-545


Tamar Perri, M.D., Shani Naor-Revel, M.D., Perry Eliassi-Revivo, M.D., Dror Lifshitz, M.D., Eitan Friedman, M.D., Ph.D., Jacob Korach, M.D.



To determine whether fertility treatments impact the risk of breast cancer in Jewish Israeli BRCA1/2 mutation carriers.


Historical cohort study.


University-affiliated tertiary medical center.


A total of 1,824 Jewish Israeli BRCA1/2 mutation carriers from a single center were stratified into 1,492 (81.8%) carriers who were not treated for infertility and 332 (18.2%) carriers who underwent fertility treatment with clomiphene citrate (n = 134), gonadotropin (n = 119), in vitro fertilization (n = 183), or a combination of treatments (n = 89).



Main Outcome Measure(s)

Hazard ratios (HR) and 95% confidence intervals (CI) for the association of breast cancer with fertility treatment and other hormonal and reproductive variables.


Breast cancer was diagnosed in 687 BRCA1/2 mutation carriers. Multivariate analysis, either of the whole group or stratified by each gene, showed no association between fertility treatment and breast cancer risk, regardless of the type of treatment (clomiphene citrate: HR 0.77, 95% CI 0.49–1.19; gonadotropin: HR 0.54, 95% CI 0.28–1.01; in vitro fertilization: HR 0.65, 95% CI 0.39–1.08; and combined treatments: HR 1.23, 95% CI 0.49–3.06). An increased breast cancer risk was associated with paternal origin of the mutation (HR 1.43, 95% CI 1.17–1.75) and use of oral contraceptives for >5 years (HR 1.62, 95% CI 1.27–2.06) in both BRCA1 and BRCA2 mutation carriers. Ovarian cancer risk was decreased with the use of any oral contraceptive (HR 0.61; 95% CI 0.46–0.82).


Fertility treatment for BRCA1/2 mutation carriers is not associated with a discernible increase in breast cancer risk.