title: Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer.
abstract: 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.
authors.affiliation: Department of Pathology, University Medical Center Hamburg Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Holst
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Stahl
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.forename: Olaf
authors.initials: O
authors.lastname: Hellwinkel
authors.forename: Zeenath
authors.initials: Z
authors.lastname: Jehan
authors.forename: Marc
authors.initials: M
authors.lastname: Wendland
authors.forename: Annette
authors.initials: A
authors.lastname: Lebeau
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Khawla
authors.initials: K
authors.lastname: Al-Kuraya
authors.forename: Fritz
authors.initials: F
authors.lastname: Jänicke
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha