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Updated: Nov 1, 2025

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Novel Agents for the Management of Endocrine Resistant Breast Cancer

Sonya Reid-Lawrence1, Ingrid A Mayer1

  • 1Division of Hematology/Oncology, Vanderbilt University Medical Center (VUMC)/Vanderbilt-Ingram Cancer Center (VICC), 2220 Pierce Ave. 777 PRB, Nashville, TN 37232, USA.

Current Breast Cancer Reports
|June 21, 2021
PubMed
Abstract

Insights

Most women with hormone receptor-positive, HER2-negative breast cancer develop endocrine resistance. This review covers resistance mechanisms and new treatments for endocrine-resistant breast cancer, including novel selective estrogen receptor degrader (SERD) development.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Hormone receptor (HR)-positive, HER2-negative breast cancer frequently develops endocrine resistance.
  • Primary or acquired resistance limits the effectiveness of standard endocrine therapy.

Purpose of the Study:

  • To review proposed mechanisms of endocrine resistance in breast cancer.
  • To discuss key advances in treating endocrine-resistant breast cancer.

Main Methods:

  • Literature review of proposed mechanisms of endocrine resistance.
  • Analysis of clinical trial data for novel therapeutic agents.

Main Results:

  • Estrogen receptor 1 (ESR1) mutations are common in patients with metastatic HR+/HER2- breast cancer after aromatase inhibitor treatment.
  • The SoFEA trial indicated improved progression-free survival (PFS) with fulvestrant compared to exemestane.
  • Fulvestrant is the sole available selective estrogen receptor degrader (SERD); oral SERDs are under investigation.

Conclusions:

  • Despite decades of progress, endocrine resistance remains a challenge in HR+/HER2- breast cancer treatment.
  • Novel agents targeting endocrine resistance mechanisms are under investigation.
Keywords:
Aromatase inhibitorBreast cancerESR1Endocrine resistanceHormone receptor positiveSERD

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