Targeted–Immunotherapy Combinations for Recurrent Breast Cancer

Recurrent breast cancer remains a major clinical challenge, accounting for the majority of breast cancer–related mortality despite significant advances in early detection and primary treatment. Tumor heterogeneity, therapeutic resistance, immune evasion, and metastatic progression contribute to disease relapse and limit long-term survival. Targeted therapies—such as HER2-directed agents, CDK4/6 inhibitors, PARP inhibitors, and PI3K/AKT pathway inhibitors—have improved outcomes in selected patient populations. Meanwhile, immunotherapy has demonstrated durable responses in a subset of patients, especially in immunogenic subtypes such as triple-negative breast cancer. Increasing evidence suggests that rational combinations of targeted therapy and immunotherapy may enhance antitumor immunity, overcome resistance mechanisms, and improve clinical benefit in recurrent disease. However, several critical clinical questions remain unresolved, including the optimal selection, sequencing, and integration of targeted and immune-based therapies, the management of treatment resistance and overlapping toxicities, and the practical implementation of accessible biomarkers for patient stratification and treatment monitoring in routine clinical practice.This Research Topic aims to highlight advances in targeted–immunotherapy combinations for recurrent breast cancer—from mechanistic insights into resistance and tumor microenvironment modulation to clinically actionable priorities such as optimizing combination strategies and implementing simple, validated biomarkers in everyday oncology practice. Contributions addressing innovative trial designs, real-world data, and precision medicine approaches are particularly encouraged to accelerate the development of more effective, personalized treatments for recurrent breast cancer.The goal of this Research Topic is to advance understanding and clinical translation of targeted–immunotherapy combination strategies for recurrent breast cancer, a setting where therapeutic resistance and disease progression remain major unmet challenges. By integrating insights from tumor biology, immunology, and precision oncology, this Special Issue aims to identify effective combination approaches that enhance antitumor immunity, overcome resistance mechanisms, and improve patient outcomes. We seek to promote interdisciplinary research spanning basic, translational, and clinical studies, including biomarker-driven patient selection, novel therapeutic targets, tumor microenvironment modulation, innovative therapeutic strategies, and new clinical trial designs. Topics of interest also include clinically oriented challenges, such as the optimal selection, sequencing, and integration of targeted and immune-based therapies, the management of treatment resistance and overlapping toxicities, and the real-world implementation of accessible biomarker. Ultimately, this Research Topic aims to accelerate the development of more durable, personalized, and evidence-based treatment strategies for patients with recurrent breast cancer, bridging laboratory discoveries with real-world clinical benefit.Subthemes of interest include, but are not limited to:• mechanistic studies of therapy-induced immune modulation;• optimal dosing, scheduling, and duration of immunotherapy in combination regimens;• clinical value and real-world implementation of accessible biomarkers;• biomarker-guided patient stratification; • subtype-specific combination strategies;• nanotechnology for recurrent breast cancer therapy;• biomaterial-driven delivery systems and combination strategies (e.g., nanoparticles, hydrogels, implants) for enhanced targeting and immunomodulation; • AI and computational models for predicting therapy response, optimizing combination regimens, and discovering novel biomarkers;• preclinical and translational models; • clinical evaluation of combination regimens. Please 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: Bianfei Shao, Changyuan Hu, Tao He Source: https://www.frontiersin.org/research-topics/80411/targeted-immunotherapy-combinations-for-recurrent-breast-cancer