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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer

Rinath Jeselsohn1,2, Carmine De Angelis3,4,5,6, Myles Brown7,8

  • 1Breast Oncology Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA. rinath_jeselsohn@dfci.harvard.edu.

Current Oncology Reports
|April 5, 2017
PubMed

Insights

ESR1 mutations in metastatic ER+ breast cancer cause endocrine treatment resistance. Further studies are needed to confirm findings and develop new therapies for these patients.

Area of Science:

  • Oncology
  • Endocrinology
  • Genetics

Background:

  • Recurrent ESR1 mutations are found in metastatic ER+ breast cancer.
  • These mutations emerge under endocrine therapy pressure.
  • Understanding their significance is crucial for treatment strategies.

Purpose of the Study:

  • To review the biological and clinical significance of ESR1 mutations.
  • To evaluate their impact on endocrine treatment efficacy.
  • To identify gaps in current knowledge and future research directions.

Main Methods:

  • Review of preclinical studies on ESR1 mutation activity.
  • Analysis of retrospective clinical trial data on ESR1 mutations in plasma ctDNA.
  • Evaluation of current literature on treatment outcomes.

Main Results:

  • Preclinical data show ESR1 mutations cause ligand-independent activity, conferring resistance to aromatase inhibitors and reduced sensitivity to tamoxifen/fulvestrant.
  • Retrospective analyses suggest ESR1 mutations are prognostic and predict resistance to aromatase inhibitors in metastatic settings.
  • ESR1 mutations are associated with poorer outcomes in ER+ metastatic breast cancer.

Conclusions:

  • ESR1 mutations confer resistance to standard endocrine therapies in metastatic ER+ breast cancer.
  • Prospective studies are essential to validate prognostic/predictive roles and guide optimal treatment.
  • Development of novel agents targeting ESR1-mutated tumors is urgently needed.
Keywords:
Circulating tumor DNAESR1 mutationsEndocrine resistanceEstrogen receptor

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