title: Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?
abstract: BACKGROUND
  Breast cancer is the most common cancer in women worldwide. Estrogen receptor (ER) positive breast cancer constitutes the majority of these cancers. Hormone therapy has significantly improved clinical outcomes for early- and late-stage hormone receptor positive breast cancer. Although most patients with early stage breast cancer are treated with curative intent, approximately 20% - 30% of patients eventually experience a recurrence. During the last two decades, there have been tremendous efforts to understand the biological mechanisms of hormone therapy resistance, with the ultimate goal of implementing new therapeutic strategies to improve the current treatments for ER positive breast cancer. Several mechanisms of hormone therapy resistance have been proposed, including genetic alterations that lead to altered ER expression or ERs with changed protein sequence.
  
  
  METHODS
  A Pubmed search was performed utilizing various related terms. Articles over the past 20 years were analyzed and selected for review.
  
  
  RESULTS
  On the basis of published studies, the frequencies ofESR1(the gene encoding ER) mutations in ER positive metastatic breast cancer range from 11% to 55%. Future larger prospective studies with standardized mutation detection methods may be necessary to determine the true incidence ofESR1mutations.ESR1amplification in breast cancer remains a controversial issue, with numerous studies either confirmed or challenged the reports ofESR1amplification. The combination of intra-tumor heterogeneity regardingESR1copy number alterations and low levelESR1copy number increase may account for these discrepancies.
  
  
  CONCLUSIONS
  While numerous unknown issues on the role ofESR1mutations in advanced breast cancer remain, these new findings will certainly deepen current knowledge on molecular evolution of breast cancer and acquired resistance to hormone therapy.
authors.affiliation: Cancer Research Center, Shahid Beheshti Univeristy of Medical Sciences, Tehran, IR Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Tabarestani
authors.affiliation: Cancer Research Center, Shahid Beheshti Univeristy of Medical Sciences, Tehran, IR Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Motallebi
authors.affiliation: Cancer Research Center, Shahid Beheshti Univeristy of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohammad Esmaeil
authors.initials: ME
authors.lastname: Akbari
keywords: Breast Cancer; ESR1 Amplification; ESR1 Mutation; Estrogen Receptor; Hormone Therapy