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    Multiple HER2 Copies Affect Response to Anthracyclines

    Patients with gene amplification have better outcome with anthracycline-containing chemotherapy regimens

    WEDNESDAY, May 17 (HealthDay News) -- Amplification of the HER2 gene or overexpression of the HER2 protein in breast cancer cells is associated with a better clinical response to anthracycline-containing chemotherapy regimens, according to a randomized study in the May 18 issue of the New England Journal of Medicine.

    Kathleen I. Pritchard, M.D., of the University of Toronto, and colleagues examined 639 tumor specimens from 710 premenopausal women with node-positive breast cancer. They assessed amplification of the gene (HER2) and overexpression of the gene's product (HER2) using fluorescence in situ hybridization, immunohistochemical analysis and polymerase chain reaction. The patients had received either cyclophosphamide, epirubicin and fluorouracil (CEF) or cyclophosphamide, methotrexate and fluorouracil (CMF).

    HER2 gene amplification was linked to a poor outcome regardless of the treatment the women had been given. However, in patients with HER2 amplification, CEF produced better relapse-free survival rates than CMF (hazard ratio, 0.52), as well as better overall survival (HR, 0.65). CEF did not demonstrate the same benefits compared to CMF in women whose tumors did not show HER2 amplification or HER2 overexpression.

    In an accompanying editorial, Martine J. Piccart-Gebhart, M.D., Ph.D., of the Universite Libre de Bruxelles in Brussels, noted that the new Canadian trial is the seventh study to attempt to link HER2 amplification to a benefit from anthracycline-containing chemotherapy regimens and is the only one to have used three parallel methods to test HER2 and HER2. "The most convincing interaction between the outcome of treatment and HER2 overexpression was found with the CEF combination used in the Canadian trial, which is the most dose-intensive of all of the anthracycline-based regimens studied," Piccart-Gebhart writes.

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