Beebeejaun Y et al.

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

Fertil Steril. 2021 Jul;116(1):198-207. doi: 10.1016/j.fertnstert.2021.01.044.

Known risk factors for breast cancer include nulliparity and prolonged exposure to estrogen and progesterone. This puts infertile women who are treated with ovarian stimulation agents at a potential increased risk of developing breast cancer. Commonly used agents to stimulate fertility include clomiphene citrate (CC) and gonadotropins. CC is an estrogen receptor modulator. Gonadotropins are hormones that act on the ovaries to stimulate ovulation. CC and gonadotropins can be used alone or in combination during the follicular phase of the menstrual cycle. One cycle of ovulation induction is equivalent to two years of menstrual cycles in terms of the high levels of estrogen achieved, which can impact tissue that is sensitive to estrogen, including breast tissue. Therefore, determining the effects of ovarian stimulation agents in infertile women on their risk of breast cancer is of clinical importance.

Beebeejaun et al. performed a literature review from 1990 to January 2020 to assess the association between ovarian stimulation agents and the risk of breast cancer in infertile women. 20 studies were identified and all were observational studies. The average follow up was 27.1 years. The meta-analysis did not find a significant increase in the risk of breast cancer in women treated with any ovarian stimulation drug for infertility compared to unexposed women in the general population. This applied to the use of clomiphene citrate or gonadotropins used alone or in combination. Beebeejaun et al. admits that no randomized controlled trials were included in the analysis, which lowers the quality of the evidence. Therefore, further studies are needed to investigate the association of ovarian stimulation drugs and the risk of breast cancer.

Women should meet with a breast specialist to discuss their risk of breast cancer. Potential risk factors include nulliparity and prolonged exposure to estrogen and progesterone. There is a concern that infertile women treated with ovarian stimulation agents are at an increased risk of breast cancer, but a review of the current literature does not support this. Hopefully, future studies will quantify breast cancer risk, if any, due to these agents.