HER-2/neu Gene Amplification and Response to Paclitaxel in Patients With Metastatic Breast Cancer

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Abstract
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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