Ovulation Induction for Infertility the Risk of Breast Cancer: A Population-Based Case-Control Study [11B

Abstract

INTRODUCTION: There is a well-established interplay between reproductive hormone levels and breast cancer. Questions remain in regards to the potential ovulation-inducing fertility treatments, which elevate serum estrogen and progesterone to supraphysiologic levels the treatment period, to affect breast tumorigenesis. METHODS: A population-based case-control study using the Clinical Practice Research Datalink (CPRD) was performed. All cases of breast cancer occurring between 1995-2013 were matched with 10 age-matched controls. Cases and controls were assessed for exposure to clomiphene or in-vitro fertilization (IVF) via their clinical records. Odds ratios and 95% confidence intervals for each exposure were computed using multivariate logistic regression, adjusted for smoking, alcohol use, BMI, oral contraceptive use, hormone replacement therapy and oophorectomy. RESULTS: The study population consisted of 27,026 cases of breast cancer and their matched controls, with 1,717 subjects having a history of clomiphene exposure and 1,137 subjects having a history of IVF. Ever-exposure to clomiphene was significantly associated with breast cancer, OR 1.34 95% CI [1.26-1.44]. IVF-exposure was similarly associated with breast cancer, OR 1.52 95% CI [1.40-1.65]. The stratified analysis indicated clomiphene was associated with pre-menopausal cancers (OR 1.59 95% CI [1.47-1.73]) but not post-menopausal malignancies (OR 0.94 95% CI [0.83-1.06]). IVF was associated with both pre- and post-menopausal cancers. CONCLUSION: Ovulation induction with clomiphene citrate and gonadotropins increases the risk of breast cancer. Women should be advised of this elevated risk understanding the associated implications.