Toxicity-Guided Treatment Sequencing in HER2-Positive Metastatic Breast Cancer: Balancing Efficacy, Quality of Life, and Drug-Related Adverse Events

The treatment landscape for HER2-positive metastatic breast cancer has expanded rapidly, with antibody-drug conjugates, tyrosine kinase inhibitors, and monoclonal antibodies now offering multiple viable lines of therapy. This creates a genuine clinical dilemma that efficacy data alone cannot resolve: when a patient is responding to treatment but experiencing significant toxicity, such as interstitial lung disease risk with trastuzumab deruxtecan, cardiotoxicity, or cumulative treatment burden, what should guide the decision to continue, switch, or discontinue therapy? This Research Topic focuses specifically on that active-treatment decision point, not on the long-term consequences patients live with after treatment ends, but on how toxicity and quality-of-life data should shape real-time sequencing choices while a patient is still being treated for metastatic disease.We welcome work that uses toxicity and quality-of-life evidence prospectively, to inform which agent to use next, rather than retrospectively, to characterize survivorship burden after therapy concludes. This includes real-world discontinuation patterns and their clinical predictors, comparative toxicity profiles between sequential lines of HER2-targeted therapy, and frameworks or decision tools that incorporate patient-reported treatment tolerability directly into sequencing algorithms. Work grounded in trial data or real-world evidence from active metastatic treatment settings is of particular interest, as is research examining how clinicians and patients weigh incremental efficacy gains against treatment-related quality-of-life costs when a next-line decision must be made.To capture the breadth of current research, we welcome articles including but not limited to:- Real-world discontinuation patterns for HER2-targeted agents (including trastuzumab deruxtecan) and their clinical or toxicity-related predictors- Comparative toxicity and tolerability profiles across sequential lines of HER2-positive metastatic breast cancer therapy- Decision frameworks and clinical tools incorporating patient-reported tolerability into treatment sequencing choices- Clinical trial and real-world evidence on balancing efficacy gains against treatment-related adverse events in active metastatic treatment- Patient and clinician decision-making processes when toxicity prompts a treatment switch during active therapyThis Research Topic is scoped to treatment-sequencing decisions during active metastatic therapy; long-term and late toxicities in post-treatment survivors, and survivorship care planning generally, fall outside its scope and are covered by a related Research Topic on breast cancer survivorship.We invite Original Research, Clinical Trials, Reviews, Mini Reviews, Perspectives, and Brief Research Reports that advance evidence-based sequencing decisions in HER2-positive metastatic breast cancer. Topic editors: Yasuyuki Kojima, Robert Wesolowski, Guy Jerusalem, Kazuki Nozawa Source: https://www.frontiersin.org/research-topics/85495/toxicity-guided-treatment-sequencing-in-her2-positive-metastatic-breast-cancer-balancing-efficacy-quality-of-life-and-drug-related-adverse-events