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Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

Andreas D Hartkopf1, Eva-Maria Grischke1, Sara Y Brucker1

  • 1Department of Women's Health, University of Tübingen, Tübingen, Germany.

Breast Care (Basel, Switzerland)
|September 28, 2020
PubMed
Abstract

Insights

Endocrine therapy resistance in estrogen receptor-positive breast cancer is a significant challenge. Understanding molecular mechanisms and developing targeted combination strategies are key to improving treatment outcomes.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Endocrine therapy is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer.
  • Tumor resistance to endocrine therapy is a common cause of treatment failure and cancer progression.
  • Identifying resistance mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • To review the molecular mechanisms and biomarkers associated with endocrine-resistant breast cancer.
  • To discuss current and emerging therapeutic strategies for overcoming endocrine resistance.
  • To highlight the challenges and future directions in managing endocrine-resistant breast cancer.

Main Methods:

  • Literature review of preclinical and clinical studies on endocrine resistance in breast cancer.
  • Analysis of molecular alterations driving resistance, including gene mutations and pathway dysregulation.
  • Evaluation of targeted therapies and combination strategies aimed at overcoming resistance.

Main Results:

  • Key resistance mechanisms include alterations in the estrogen receptor 1 (ESR1) gene and the PIK3CA/mTOR pathway.
  • Inhibitors targeting CDK4/6, mTOR, and PI3K pathways show promise in combination with endocrine therapy.
  • Emerging therapeutic approaches are under development to address diverse resistance profiles.

Conclusions:

  • Overcoming primary and acquired endocrine resistance remains a critical clinical challenge.
  • The multifaceted nature of endocrine resistance necessitates personalized combination and sequencing strategies.
  • Continued research into molecular drivers and therapeutic interventions is essential for advancing ER+ breast cancer treatment.
Keywords:
Breast cancerEndocrine resistanceEndocrine treatmentMetastases

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