Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer. (December 2022)

• Record Type: Journal Article
• Authors: Aapro, Matti; Cardoso, Fatima; Curigliano, Giuseppe; Eniu, Alexandru; Gligorov, Joseph; Harbeck, Nadia; Mueller, Andreas; Pagani, Olivia; Paluch-Shimon, Shani; Senkus, Elzbieta; Thürlimann, Beat; Zaman, Khalil
• Is Part Of: Breast. Volume 66(2022)
• Page Start: 145
• Page End: 156
• Publication Date: 2022-12
• Subjects: HER2 -- Advanced breast cancer -- Monoclonal antibody -- Brain metastasis -- Tyrosine kinase inhibitor -- Antibody-drug conjugate; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2022.07.011
• Languages: English
• ISSNs: 0960-9776

Abstract

Abstract: Human epidermal growth factor receptor 2 oncogene (HER2-positive) overexpression/amplification occurs in less than 20% of breast cancers and has traditionally been associated with poor prognosis. Development of therapies that target HER2 has significantly improved outcomes for patients with HER2-positive advanced breast cancer (ABC). Currently available HER2-targeted agents include the monoclonal antibodies trastuzumab, pertuzumab, and margetuximab, the small-molecule inhibitors lapatinib, tucatinib, neratinib, and pyrotinib, as well as the antibody-drug conjugates trastuzumab emtansine and trastuzumab deruxtecan. Optimal sequencing of these agents in the continuum of the disease is critical to maximize treatment outcomes. The large body of clinical evidence generated over the past 2 decades aids clinicians in treatment decision-making. However, patients with HER2-positive ABC and specific disease characteristics and/or comorbidities, such as leptomeningeal disease, brain metastases, or cardiac dysfunction, are generally excluded from large randomized clinical trials, and elderly or frail patients are often underrepresented. In addition, there is great inequality in the accessibility of approved drugs across countries. This article addresses various challenging clinical situations when treating patients with HER2-positive ABC. The objective is to provide guidance to clinicians on how and when HER2-targeted therapies and additional treatments can be best implemented in routine clinical practice, on the basis of existing clinical evidence and expert opinion where needed. Highlights: HER2-targeted therapies have significantly improved outcomes for patients with ABC Ideal sequencing of regimens is key to maximize treatment benefits New HER2-targeted agents are used at earlier stages in BC treatment Clinical evidence for treatment of special populations with ABC is lacking Approved drugs are not accessible in all countries