Abstract
Most women with hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) breast cancer will ultimately develop endocrine-resistant disease, either primary or acquired. This review will discuss the proposed mechanisms underlying endocrine resistance and key advances in the treatment of endocrine-resistant breast cancer. Estrogen receptor 1 mutations (ESR1) occur in the majority of patients with HR+/HER2- metastatic breast cancer after prolonged exposure to aromatase inhibitors. Data from the SoFEA trial showed that patients had improved progression-free survival (PFS) after taking fulvestrant compared with exemestane. Fulvestrant is currently the only selective estrogen receptor degrader (SERD) available and development of oral novel SERDs with higher bioavailability and potency are currently being investigated. Despite significant advances in the treatment of HR+/HER2- breast cancer over the past four decades, a significant proportion of patients do still develop endocrine resistance following optimal endocrine therapy. In this review, we aim to provide an overview of the different classes of novel agents currently being investigated to overcome endocrine resistance.
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