Implication of environmental estrogens on breast cancer treatment and progression.

Breast cancer is the most diagnosed malignancy among women in the United States. Approximately 70% of breast tumors express estrogen receptor alpha and are deemed ER-positive. ER-positive breast tumors depend upon endogenous estrogens to promote ER-mediated cellular proliferation. Decades of research have led to a fundamental understanding of the role ER signaling in this disease and this knowledge has led to significant advancements in the clinical use of antiestrogens for breast cancer treatment. However, adjuvant breast cancer recurrence and metastatic disease progression due to endocrine therapy resistance are prominent and unresolved issues. The established role that estrogens play in breast cancer pathogenesis explains why some patients initially respond to endocrine therapy but also why a significant number of patients become refractory to antiestrogen treatment. It is been hypothesized that exposure to environmental steroid hormone mimics and/or acquired mechanisms of resistance may explain why endocrine therapy fails in a subset of breast cancer patients. This review will highlight: 1) the relationship between ER signaling and breast cancer pathogenesis, 2) the implication of environmental exposures on steroid hormone regulated processes including breast cancer, and 3) the unresolved issue of endocrine therapy resistance.