Escalation and De-escalation Strategies of Adjuvant Endocrine Therapy in Early Breast Cancer

The management of hormone receptor–positive (HR+) early breast cancer has long relied on adjuvant endocrine therapy, which is recognised as a fundamental intervention to reduce recurrence risk and improve survival outcomes. While the efficacy of these therapies is well established, ongoing debates persist regarding the optimal duration and intensity, particularly as more personalised treatment approaches emerge. Extending therapy beyond five years has demonstrated the ability to prevent late relapse, yet it is accompanied by heightened adverse effects, greater risk of treatment fatigue, and a negative impact on quality of life. Premature discontinuation remains problematic, correlating with inferior outcomes, especially among premenopausal women and those with aggressive disease profiles. Meanwhile, recent advances in targeted therapies, such as CDK4/6 inhibitors, PI3K/AKT inhibitors, and oral selective estrogen receptor degraders (SERDs), are reshaping the therapeutic landscape and calling for a reevaluation of conventional adjuvant strategies.Notably, the integration of targeted agents alongside endocrine therapy in the adjuvant setting offers new possibilities for overcoming resistance and tailoring interventions based on an increasingly sophisticated understanding of tumour biology. Initial studies show that these combinations may further reduce recurrence, but careful consideration is required in terms of appropriate patient selection, duration of therapy, sequencing, and the balance between efficacy and long-term safety. There also remains significant heterogeneity in clinical trial endpoints, biomarker validation, and translation of findings into routine practice. A major gap persists in defining the optimal escalation or de-escalation pathways that account for individual clinical, pathological, and molecular risk, highlighting the need for prospective evaluation of personalised strategies. The rise of molecular tools, including genomic signatures and circulating tumour DNA, presents promising avenues for risk stratification and minimal residual disease assessment, yet their role in everyday clinical decisions warrants further investigation.This Research Topic aims to synthesise translational and clinical evidence to define a framework for the individualisation of adjuvant endocrine therapy in early breast cancer. Central goals include clarifying patient subsets that derive most benefit from treatment escalation or extension versus those suitable for early withdrawal, examining mechanisms of endocrine resistance and targeted combination approaches, and establishing the clinical validity of emerging biomarkers to guide therapy decisions. We seek to promote a multidisciplinary and patient-centred dialogue that weighs efficacy, toxicity, adherence, and quality of life, with an eye towards pragmatic adoption and cost-effectiveness.To gather further insights into optimising adjuvant endocrine therapy for HR+ early breast cancer, we welcome articles addressing, but not limited to, the following themes:- Criteria and tools for personalising therapy duration and intensity.- Predictive and prognostic biomarkers, including genomic signatures and circulating tumour DNA.- Integration and sequencing of targeted agents with endocrine therapy.- Biological mechanisms underlying endocrine resistance and means to overcome it.- Strategies for enhancing adherence and minimising side effects.- Patient-reported outcomes and real-world data on therapy effectiveness.- Translational research linking detection of minimal residual disease to treatment adaptation.- Health economic analyses and policy implications of treatment optimisation.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.Dr. Arecco received a travel grant from AstraZeneca and research funding to his institution from Gilead and Pfizer.Prof. Kimmick received grants from Novartis and Pfizer and research funding from Bionovo, PUMA, and Roche.Dr. Buonaiuto declared no conflicts of interest. Topic editors: Luca Arecco, Gretchen Kimmick Source: https://www.frontiersin.org/research-topics/78031/escalation-and-de-escalation-strategies-of-adjuvant-endocrine-therapy-in-early-breast-cancer