Endocrine therapy in the preoperative setting and strategies to overcome resistance

Endocrine therapy remains the mainstay for treatment of hormone receptor-positive breast cancer in both adjuvant and metastatic settings. Due to the cytostatic property of endocrine therapy, cytotoxic chemotherapy is more commonly used for cytoreduction in preoperative setting to promote breast-conserving surgery. Nevertheless, recent clinical trials demonstrated that preoperative endocrine therapy can also be used to facilitate breast conservation in patients with locally advanced breast cancer, particularly in postmenopausal women with low proliferative tumors. Multiple markers have been shown to be predictive of endocrine responsiveness, including estrogen and progesterone receptor expression as well as other molecular profiles such as the 21-gene recurrence score assay and PAM-50 assay. The preoperative setting offers a unique situation to rapidly prioritize novel treatment combination and to identify the mechanisms of resistance. Several strategies to overcome resistance, including co-targeting other signaling pathways, particularly human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor (VEGF), and PI3K/Akt/mTOR, are discussed in this review article.