title: HER-2 gene amplification can be acquired as breast cancer progresses.
abstract: Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.
authors.affiliation: Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
authors.forename: Debasish
authors.initials: D
authors.lastname: Tripathy
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Barbara
authors.initials: B
authors.lastname: Haley
authors.forename: Steve
authors.initials: S
authors.lastname: Perkins
authors.forename: Peter
authors.initials: P
authors.lastname: Beitsch
authors.forename: Amanullah
authors.initials: A
authors.lastname: Khan
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.forename: Cynthia
authors.initials: C
authors.lastname: Osborne
authors.forename: Eugene
authors.initials: E
authors.lastname: Frenkel
authors.forename: Susan
authors.initials: S
authors.lastname: Hoover
authors.forename: Marilyn
authors.initials: M
authors.lastname: Leitch
authors.forename: Edward
authors.initials: E
authors.lastname: Clifford
authors.forename: Ellen
authors.initials: E
authors.lastname: Vitetta
authors.forename: Larry
authors.initials: L
authors.lastname: Morrison
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
authors.forename: Timothy
authors.initials: T
authors.lastname: Fleming
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Thomas
authors.initials: T
authors.lastname: Tucker
authors.forename: Nancy
authors.initials: N
authors.lastname: Lane
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Uhr
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068878:Trastuzumab