Navigating ADC Use and Sequencing in HER2+ Breast Cancer

Under current NCCN guidelines as of mid-December 2025, patient selection for neoadjuvant antibody-drug conjugate (ADC) therapy in early HER2-positive breast cancer is guided by disease stage, tumor burden, and risk factors for recurrence. High-risk patients or those less likely to achieve a pathologic complete response with standard neoadjuvant therapy may be considered for ADC integration. In the metastatic setting, treatment pathways after progression on ADCs remain an area of active clinical discussion. While some evidence supports switching to alternative HER2-targeted agents or clinical trial enrollment, there is no universally established sequence, creating ongoing uncertainty for clinicians. Decisions are individualized, factoring prior response, toxicity profiles, and patient preferences. Emerging data and future studies are expected to clarify optimal post-ADC sequencing and help standardize care strategies across both early and metastatic HER2-positive disease.