Clinical Challenges in the Management of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review

AbstractEndocrine therapy (ET) is integral to the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2 −) metastatic breast cancer (MBC). Aromatase inhibitors (AIs; e.g., anastrozole, letrozole, exemestane), selective estrogen receptor modulators (e.g., tamoxifen), and the selective estrogen receptor degrader, fulvestrant, inhibit tumor cell proliferation by targeting ER signaling. However, the eff icacy of ET could be limited by intrinsic and acquired resistance mechanisms, which has prompted the development of targeted agents and combination strategies. In recent years, the treatment landscape for HR+, HER2− MBC has evolved rapidly. AIs, historically the first-line treatment for postmenopa usal patients with HR+, HER2− MBC, have been challenged by more effective ET, such as fulvestrant alone or in combination with an AI, and the cyclin-dependent kinase (CDK)4/6 inhibitors, which have increasingly become the new standard of care. For endocrine-resistant disease (≥ second-line), c linical trials demonstrated that the mammalian target of rapamycin inhibitor, everolimus, enhanced the efficacy of exemestane or fulvestrant after progression on an AI. CDK4/6 inhibitors in combination with fulvestrant have demonstrated superior progression-free survival and overall survival versus fulvestrant alone. Recently, the combination of fulvestrant with alpelisib in phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutated HR+...
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research