Endocrine Resistance in Hormone Receptor-Positive Breast Cancer: Mechanisms, Biomarkers, and Therapeutic Strategies

Hormone receptor-positive breast cancer remains the most common subtype of breast cancer, and endocrine therapy has substantially improved outcomes across both early and advanced disease settings. However, intrinsic and acquired resistance to endocrine treatment continues to limit durable clinical benefit and represents a major challenge in patient management. A deeper understanding of the biological basis of endocrine resistance is therefore essential to improve risk stratification, guide treatment selection, and support the development of more effective therapeutic strategies.This Research Topic will explore the diverse mechanisms that drive endocrine resistance in hormone receptor-positive breast cancer, spanning tumor-intrinsic, microenvironmental, and systemic determinants of treatment failure. Areas of interest include, but are not limited to, alterations in estrogen receptor signaling, ESR1 mutations and other genomic drivers, epigenetic reprogramming, adaptive pathway activation, cell cycle dysregulation, metabolic plasticity, tumor heterogeneity, and crosstalk with growth factor and immune-related signaling networks. Greater insight into these processes may reveal clinically relevant vulnerabilities and refine current disease models.A second major focus of this Topic is the identification and validation of biomarkers associated with endocrine sensitivity, resistance, progression, and therapeutic response. This includes tissue-based, circulating, and multi-omic biomarkers, as well as approaches that integrate molecular profiling, functional assays, and longitudinal disease monitoring. Particular attention may be given to biomarkers that inform prognosis, predict benefit from targeted combinations, or enable earlier detection of emerging resistance.This Topic will also highlight evolving therapeutic strategies designed to overcome or delay endocrine resistance. Relevant themes include the development and clinical translation of novel endocrine agents, rational combination approaches, targeted therapies, and biomarker-guided treatment frameworks. Contributions addressing preclinical models, translational evidence, and mechanisms of response or resistance to existing and emerging interventions are especially welcome.By bringing together current advances in biology, biomarker discovery, and therapeutic innovation, this Research Topic aims to provide a focused overview of the field and stimulate progress toward more precise and durable treatment approaches for patients with hormone receptor-positive breast cancer.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: Ahmet Acar, Silvia Mihaela Ilie, LAURENTIA GALES Source: https://www.frontiersin.org/research-topics/81951/endocrine-resistance-in-hormone-receptor-positive-breast-cancer-mechanisms-biomarkers-and-therapeutic-strategies