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Purpose of Review <p>Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) that have progressed on endocrine therapy had limited treatment options beyond chemotherapy. This review aims to summarize recent updates in the treatment algorithm for endocrine-resistant mBC and management of treatment-related adverse events.</p> Recent Findings <p>Hyperglycemia, rash, and diarrhea are adverse effects of alpelisib and capivasertib, kinase inhibitors that target phosphatidylinositol-3-kinase/AKT pathway mutated HR+ HER2- tumors. Trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate (ADC), and sacituzumab govitecan, a first-in-class trophoblast cell-surface antigen 2-directed ADC, have both demonstrated clinical benefit in HER2-low and -ultralow tumors. Optimal sequencing of ADCs is unknown.</p> Summary <p>Notable treatment advancements include newer oral oncolytics and ADCs. While these therapies have demonstrated clinical efficacy in the second-line setting and beyond, their side effect profiles require management from a multidisciplinary team. As new drugs and combination regimens continue to develop, it remains crucial to consider toxicity and burden to the patient.</p>

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Updates in Endocrine-Resistant Metastatic Breast Cancer and Treatment-Related Adverse Event Management

  • 期刊论文

  • 发表日期：

    2025年12月11日

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  • Gaybrielle R. Moore,
  • Annalise E. Labatut

摘要

Purpose of Review

Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) that have progressed on endocrine therapy had limited treatment options beyond chemotherapy. This review aims to summarize recent updates in the treatment algorithm for endocrine-resistant mBC and management of treatment-related adverse events.

Recent Findings

Hyperglycemia, rash, and diarrhea are adverse effects of alpelisib and capivasertib, kinase inhibitors that target phosphatidylinositol-3-kinase/AKT pathway mutated HR+ HER2- tumors. Trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate (ADC), and sacituzumab govitecan, a first-in-class trophoblast cell-surface antigen 2-directed ADC, have both demonstrated clinical benefit in HER2-low and -ultralow tumors. Optimal sequencing of ADCs is unknown.

Summary

Notable treatment advancements include newer oral oncolytics and ADCs. While these therapies have demonstrated clinical efficacy in the second-line setting and beyond, their side effect profiles require management from a multidisciplinary team. As new drugs and combination regimens continue to develop, it remains crucial to consider toxicity and burden to the patient.