Unraveling the Spectrum of Treatment Efficacy in Breast Cancer: Biology, Biomarkers, and Therapeutic Opportunities

Breast cancer treatment response spans a wide biological and clinical spectrum, ranging from exceptional and durable benefit to primary resistance and early progression. This variability is observed across the disease continuum, from early-stage and neoadjuvant settings to advanced and metastatic disease. Although major advances in targeted therapy, endocrine therapy, immunotherapy, and antibody-drug conjugates have improved outcomes across several breast cancer subtypes and stages, response remains highly heterogeneous. Some patients experience profound and long-lasting benefit, whereas others show intrinsic resistance from the outset despite receiving standard-of-care treatment. This variability reflects a complex interplay of tumor-intrinsic features, microenvironmental factors, host-related influences, and treatment-specific mechanisms of sensitivity and resistance. In recent years, growing attention has been given to the biological basis of exceptional responders, the molecular drivers of primary resistance, and the clinical and translational opportunities that arise from studying both extremes of the response spectrum, across early-stage, locally advanced, and metastatic breast cancer. A deeper understanding of these processes is essential to improve patient stratification, identify predictive biomarkers, overcome resistance mechanisms, and guide more individualized therapeutic strategies in breast cancer.We welcome contributions spanning the full continuum of breast cancer research, including reviews, basic, preclinical, translational, and clinical studies that advance our understanding of treatment sensitivity, exceptional benefit, and therapeutic resistance across all disease stages.Areas of particular interest include:• Exceptional responders and long-term durable benefit in breast cancer, from early-stage to advanced disease• Primary resistance and mechanisms of intrinsic non-response• Molecular, cellular, and functional determinants of treatment sensitivity and resistance identified through preclinical models• Predictive and prognostic biomarkers of treatment response• Tumor genomic, transcriptomic, proteomic, metabolomic, and spatial features associated with response• Tumor microenvironment, immune contexture, stromal interactions, and host-related determinants of response• Experimental models, organoids, patient-derived xenografts, and innovative platforms for studying response and resistance• Endocrine therapy, targeted therapy, chemotherapy, immunotherapy, antibody-drug conjugates, and emerging therapeutic modalities across early-stage and advanced settings• Resistance evolution, tumor plasticity, clonal dynamics, and adaptive escape mechanisms• Novel therapeutic targets and strategies emerging from mechanistic and translational research• Clinical strategies to overcome resistance and improve response durability• Translational approaches that connect laboratory discoveries with patient outcomes and precision oncology applicationsPlease note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Cinzia Solinas, Anindita Chakrabarty, Ravindra Waykar, Zuzana Hlavata Source: https://www.frontiersin.org/research-topics/84673/unraveling-the-spectrum-of-treatment-efficacy-in-breast-cancer-biology-biomarkers-and-therapeutic-opportunities