Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer

Nat Genet. 2007 May;39(5):655-60. doi: 10.1038/ng2006. Epub 2007 Apr 8.


Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Amplification / genetics*
  • Gene Dosage / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA


  • ESR1 protein, human
  • Estrogen Receptor alpha