HER2-positive metastatic breast cancer: a comprehensive review

• Published in: Clinical advances in hematology & oncology Vol. 19; no. 1; pp. 40 - 50
• Main Authors: Exman, Pedro, Tolaney, Sara M
• Format: Journal Article
• Language: English
• Published: United States 01.01.2021
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - secondary; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Bridged-Ring Compounds - therapeutic use; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Female; Humans; Immunoconjugates - therapeutic use; Neoplasm Metastasis; Oxazoles - therapeutic use; Pyridines - therapeutic use; Quinazolines - therapeutic use; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Taxoids - therapeutic use; Trastuzumab - therapeutic use
• ISSN: 1543-0790

Cases of human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent approximately 15% to 20% of all breast cancers. Historically, this subtype of breast cancer was associated with an increased risk for the development of systemic and brain metastases and poor overall survival. The introduction of trastuzumab dramatically changed the outcomes of patients with HER2-positive disease, with many demonstrating outcomes similar to those of patients with luminal tumors. Currently, the first-line standard of care for patients with HER2-positive metastatic breast cancer is dual HER2 antibody therapy with pertuzumab/trastuzumab plus a taxane. After progression, the standard of care is trastuzumab emtansine (T-DM1). Although the treatment choices for patients whose disease has progressed on these agents are more limited, promising new drugs have emerged as effective options, including tucatinib and trastuzumab deruxtecan, which were recently approved by the US Food and Drug Administration. Finding the best treatment sequencing for each patient, developing reliable predictive biomarkers, and understanding the mechanisms of resistance to these drugs are necessary to maximize patient outcomes and quality of life. In this review, we analyze the management strategies for metastatic HER2-positive breast cancer, address specific situations, such as the treatment of patients with brain metastases, and discuss future directions in the treatment of this subtype.