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Neoadjuvant Endocrine Therapy in Clinical Practice: A Review. JAMA oncology IMPORTANCE:In clinical practice, neoadjuvant endocrine therapy (NET) is rarely used despite being an effective treatment modality able to downstage tumors and facilitate breast-conserving surgery. OBSERVATIONS:Using data from studies conducted since 2000, we provide readers with a critical in-depth review on clinical aspects related to the application of NET in the treatment of hormone receptor (HR)-positive/ERBB2 (formerly HER2)-negative breast cancer. This includes an overview of patient-selection criteria, regimen choice, treatment duration, evaluation of response by imaging, interpretation of pathology after treatment, and surgical considerations. Areas of controversy include the use of gene-expression tests for patient selection, treatment of premenopausal women, surgical management of the axilla after NET, and adjuvant systemic therapy decision-making, including the use of chemotherapy. CONCLUSIONS AND RELEVANCE:NET is an optimal treatment modality for a considerable proportion of postmenopausal women diagnosed with HR-positive tumors. The treatment landscape for HR-positive breast cancer is evolving, with novel agents and the growing use of gene expression profiling to define treatment selection. As such, it is likely that NET use will increase and the practical considerations outlined here will become more important. 10.1001/jamaoncol.2021.2132