Effects of Endocrine Interventions Targeting ERα or PR on Breast Cancer Risk in the General Population and Carriers of BRCA1/2 Pathogenic Variants

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers.