The evolving treatment of HER2-positive early breast cancer

Abstract

HER2-positive early breast cancer (EBC) accounts for 15–20% of breast cancer cases and is characterized by aggressive biology, though outcomes have significantly improved with HER2-directed therapies. This narrative review summarizes contemporary approaches to personalize systemic treatment of HER2-positive EBC through de-escalation and escalation strategies. In stage I disease, abrogated regimens such as paclitaxel plus trastuzumab provide excellent long-term outcomes, while ongoing studies have, and are, evaluating chemotherapy-free strategies and shorter treatment durations. In stage II–III disease, neoadjuvant therapy facilitates response-adapted management using pathologic complete response (pCR) as a functional biomarker to either de-escalate or escalate systemic therapy (including standard and emerging treatment options). Increasing evidence supports omission of anthracyclines and selective carboplatin use to minimize toxicity without compromising efficacy. Biomarkers—including intrinsic subtypes, tumor-infiltrating lymphocytes, circulating tumor DNA, and advanced imaging modalities such as FDG-PET and MRI—are increasingly included in risk stratification and treatment selection. Adaptive platform trials further support biomarker-driven initiatives to personalize care. Ongoing efforts aim to refine patient selection, optimizing outcomes while minimizing treatment-related toxicity, which is critical to driving further advancements in the field.