Abstract
Nowadays, neoadjuvant endocrine therapy is a clinically acceptable (and sometimes preferred) strategy in patients with operable estrogen receptor-positive (ER+) breast cancer. Despite the overall effectiveness of endocrine therapy in breast cancer in all settings, de novo (primary) and acquired (secondary) endocrine therapy resistance remains a major clinical problem. Neoadjuvant endocrine therapy trials for breast cancer are not only a great opportunity to determine which ER+ breast cancers can be treated without chemotherapy, but also a great strategy to develop insights into the biologic basis for the efficacy of estrogen-receptor-targeting agents, alone or in combination, in an effort to counteract resistance to endocrine therapy and discover actionable molecular targets that can be the focus of future drug discovery efforts and/or translational/clinical investigation in ER+ breast cancers.