The emerging role of ESR1 mutations in luminal breast cancer as a prognostic and predictive biomarker of response to endocrine therapy

Irene De Santo, Amelia McCartney, Luca Malorni, Ilenia Migliaccio, Angelo Di Leo

Research output: Contribution to journalReview ArticleResearchpeer-review

56 Citations (Scopus)

Abstract

Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.

Original languageEnglish
Article number1894
Number of pages15
JournalCancers
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2019
Externally publishedYes

Keywords

  • Breast cancer
  • Endocrine-resistance
  • ESR1 mutations
  • Liquid biopsy
  • Prognostic and predictive biomarker
  • SERD

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