Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis

Objective: To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Patient(s): Women without any previous history of breast cancer undergoing ovarian stimulation.

Intervention(s): Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls.

Main outcome measure(s): New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs.

Result(s): Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I² = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination.

Conclusion(s): The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer.