Neoadjuvant endocrine therapy in breast cancer: Current knowledge and future perspectives

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2−) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2− BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.