Endocrine Therapy Resistance: Current Status, Possible Mechanisms and Overcoming Strategies

Endocrine therapy has developed rapidly and become most effective and clearly target form of adjuvant therapy for hormone sensitive breast cancer. Adjuvant endocrine therapy for breast cancer can be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and selective estrogen receptor down-regulators (SERDs). Unfortunately, tumor cells may develop resistance to endocrine therapy, which become a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptor and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, the progression of resistance to endocrine therapy supposes to be a progressive, step-wise procedure and the underlying mechanism remains unclear. In this review, we would summarize the possible biology and molecular mechanisms that underlie endocrine resistance, and also some novel strategies to overcoming this issue. Keywords: Endocrine therapy, Endocrine resistance, Estrogen receptor, HER2, AIs, SERMs, SERDs