HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.

HER2-positive breast cancer accounts for approximately 15% of all breast cancer cases and represents an aggressive histological subtype, often associated with poorer prognosis. The advent of HER2-targeted therapies has significantly improved outcomes for patients with HER2-positive breast cancer. However, both primary and acquired resistance remain substantial challenges in clinical practice. Over the past decades, numerous underlying mechanisms of HER2-targeted therapy resistance have been uncovered, and various strategies to overcome them have been proposed. The advancement of novel technologies has further revolutionized both therapeutic approaches and investigative methods. In this review, we summarize the fundamental biology of HER2, explore the mechanisms of resistance, discuss strategies to overcome resistance, and review predictive tools for evaluating treatment efficacy.