© 2004 by Oxford University Press
© 2004 Oxford University Press
ARTICLE |
HER-2/neu Gene Amplification and Response to Paclitaxel in Patients With Metastatic Breast Cancer
Affiliations of authors: Division of Hematology–Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, and Jonsson Comprehensive Cancer Center, Los Angeles, CA (GEK, SD, LR, GP, MDP, DJS); Department of Biomathematics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles (HJW); Breast Cancer Study Group, Arbeitsgemeinschaft für Gynäkologische Onkologie, Germany (CT, HJL, MU, WK, HE, ADB, SO, DS, VM, GVM, FJ)
Correspondence to: Dennis J. Slamon, MD, PhD, University of California, Los Angeles, Peter Ueberroth Bldg., 3360B, 10945 Le Conte Ave., Los Angeles, CA 90095-7077 (e-mail: dslamon{at}mednet.ucla.edu)
Background: HER-2/neu overexpressionappears to be associated with improved response to anthracycline-based chemotherapy, but its association with response to taxane-based chemotherapy is unclear. In this retrospective subset analysis of patients with metastatic breast cancer enrolled in a randomized treatment trial, we investigated the response of patients with known HER-2/neu status to treatment with taxane-based epirubicin–paclitaxel (ET) chemotherapy compared with treatment with epirubicin–cyclophosphamide (EC) chemotherapy. Methods: HER-2/neu status (positive [i.e., HER-2/neu amplification] or negative [i.e., no HER-2/neu amplification]) of archival specimens of primary tumors from 297 patients with metastatic breast cancer was determined by use of fluorescence in situ hybridization. Associations between HER-2/neu status and the efficacy of randomly assigned chemotherapy (ET versus EC) were investigated. All statistical tests were two-sided. Results: Patients with HER-2/neu–positive tumors had a statistically significantly greater objective response rate than patients with HER-2/neu–negative tumors to treatment with ET (76% versus 50%, respectively; P = .005) but not to treatment with EC (46% versus 33%; P = .130). The objective response rate associated with ET was greater than that associated with EC for both HER-2/neu–positive tumors (76% versus 46%; P = .004) and HER-2/neu–negative tumors (50% versus 33%; P = .002). However, the improvement in the objective response rate associated with ET, compared with that associated with EC, was greater for patients with HER-2/neu–positive tumors (adjusted odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.48 to 8.92; P= .005) than for patients with HER-2/neu–negative tumors (adjusted OR = 1.92, 95% CI = 1.01 to 3.64; P= .046). Among patients with HER-2/neu–positive tumors, those who received ET had better progression-free survival and overall survival than those who received EC (for progression-free survival, adjusted relative risk [RR] = 0.65, 95% CI = 0.42 to 1.02; P= .062; for overall survival, adjusted RR = 0.60, 95% CI = 0.36 to 1.02; P= .059). However, among patients with HER-2/neu–negative tumors, those who received ET and those who received EC had similar progression-free survival and overall survival. Conclusions: HER-2/neu amplification does not adversely influence response to first-line chemotherapy with either ET or EC. Furthermore, a taxane-containing regimen such as ET may provide a preferential benefit to patients with HER-2/neu–positive tumors.
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