Systemic Therapy in Breast Cancer: New Perspectives and Advances in Validated Escalation and De-escalation Strategies

Personalized medicine has become an increasingly central pillar in the management of breast cancer. As our understanding of tumor biology deepens, it is now well established that breast cancer is not a single disease but a heterogeneous collection of subtypes, each carrying distinct molecular signatures, prognoses, and therapeutic vulnerabilities. Patients fall along a wide spectrum of risk, from those with highly aggressive disease requiring intensive systemic intervention, to those with indolent disease for whom treatment de-escalation may spare unnecessary toxicity without compromising outcomes, and in recent years have witnessed significant evolution in clinical guidelines, driven by landmark clinical trials that have provided the evidence base for more individualized treatment strategies. These advances have enabled clinicians to tailor systemic therapy with greater precision, such as escalating treatment intensity for patients at high risk of recurrence or treatment resistance while safely reducing therapeutic burden for those in whom standard or abbreviated regimens prove equally effective. This shift toward a risk-stratified, response-adapted framework represents a paradigm change in how systemic breast cancer therapy is both conceived and delivered.Importantly, escalation and de-escalation of systemic therapy do not occur in isolation: treatment intensity and response also shape decisions in the local management of disease. This Research Topic therefore welcomes contributions examining how systemic therapy strategies influence the extent and nature of local treatment, including the scope of surgery on the primary tumor and axillary nodes, and the type and extent of radiotherapy. We are particularly interested in work exploring how response to systemic treatment, including pathological complete response and residual disease burden, informs de-escalation of surgical extent, axillary staging and management, and radiotherapy fields or dose, as well as how anticipated local treatment plans may in turn inform systemic therapy decisions.This Research Topic seeks to consolidate and advance the growing body of evidence underpinning escalation and de-escalation strategies across breast cancer subtypes, encompassing both systemic and local therapy. We welcome contributions that explore the biological and clinical rationale behind guideline changes in specific patient subgroups, as well as those presenting trial results that have directly informed current practice. The role of predictive and prognostic biomarkers in guiding treatment decisions is of particular interest, including genomic assays, pathological response criteria, and emerging molecular targets that may refine patient selection for escalated or de-escalated approaches, whether systemic or local. We particularly encourage submissions identifying or validating biomarkers capable of distinguishing patients who require more aggressive therapy from those in whom treatment de-escalation may be safely pursued, at either the systemic or local level.The neoadjuvant setting represents a particularly dynamic area in this context, offering a unique window into treatment response and residual disease biology, and contributions addressing this strategy, including its implications for subsequent surgical and radiotherapy decisions, are strongly encouraged. Equally, we welcome perspectives on ongoing clinical trials poised to further reshape treatment algorithms, as well as well-reasoned proposals for novel escalation or de-escalation strategies supported by robust scientific rationale.All original research generated by authors working in this field is of significant interest to this collection, and we encourage submissions that reflect the full breadth of breast cancer therapy spanning early-stage, locally advanced, and metastatic disease in addition to studies addressing the interplay between systemic and local treatment approaches.Dr. Mario Campone has declared his conflicts of interest: Advisory Board: Novartis, Lilly, Pfizer, MSD, Daiichi-Sankyo.Consultant: Astra Zeneca, Novartis, Daiichi-Sankyo, PET-Therapy.Speaker Bureau: Novartis, Lilly;Travel: Pfizer, Novartis,Roche, Astra Zeneca,Daiichi-SankyoPlease 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: Guy Jerusalem, ANTONIO LLOMBART-CUSSAC, Mario Campone Source: https://www.frontiersin.org/research-topics/83847/systemic-therapy-in-breast-cancer-new-perspectives-and-advances-in-validated-escalation-and-de-escalation-strategies