@article{TBCR112016,
author = {Hitomi Sakai and Junji Tsurutani},
title = {Therapeutics and toxicity management of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: a narrative review},
journal = {Translational Breast Cancer Research},
volume = {7},
number = {0},
year = {2026},
keywords = {},
abstract = {Background and Objective: Development of anti-human epidermal growth factor receptor 2 (HER2) therapy has dramatically changed the prognosis of HER2-positive metastatic breast cancer (MBC), which is intrinsically aggressive. The objective of this review is to summarize the current treatment options and supportive care strategies for patients with HER2-positive MBC.Methods: This review discusses the available evidence for the systemic treatment of HER2 positive MBC, management of central nervous system (CNS) metastases, and supportive care for patients receiving anti-HER2 therapy.Key Content and Findings: Trastuzumab and pertuzumab combined with taxane has been the standard first-line treatment, supported by the CLEOPATRA trial. Trastuzumab deruxtecan (T-DXd) has shown superior efficacy compared to trastuzumab emtansine (T-DM1) and is currently the preferred second-line treatment. The DESTINY-Breast09 study has suggested that T-DXd plus pertuzumab may outperform the current first-line regimens. Tucatinib could improve the survival of patients with brain metastases and may be a key option for later lines. Brain metastases remain a major challenge, affecting up to 50% of the patients. T-DXd has demonstrated intracranial efficacy in both clinical trials and real-world studies, including studies involving patients with leptomeningeal diseases. Supportive care for patients with cardiac toxicity, nausea, vomiting, and interstitial lung disease (ILD) is essential. The development of anti-HER2 therapies, including T-DXd, has dramatically transformed the treatment landscape for HER2-positive MBC. However, treatment options after T-DXd progression and long-term management of side effects remain ongoing challenges.Conclusions: T-DXd has redefined the standard of care for HER2-positive MBC, potentially improving outcomes even with CNS metastases. However, post-T-DXd strategies and management of long-term toxicities remain key challenges.},
issn = {2218-6778}, url = {https://tbcr.amegroups.org/article/view/112016}
}