Recent trials of induction chemotherapy in bulky operable breast cancer have shown much higher pathological complete response (pCR) rates with trastuzumab-driven combinations. However, it is useful to take into account the specific chemosensitivity of HER-2-positive tumors. The aim of this study was to assess the pCR rate according to HER-2 status in response to chemotherapy, without an anti-HER-2 specific biological agent, in 710 operable breast cancer patients. Since 1982, these patients have been treated with several different neoadjuvant chemotherapy combinations. During this period, HER-2 overexpression was most often not assessed. Subsequently, we assessed HER-2 expression using archival paraffin-embedded tissue. A technically usable specimen was available for 413 of the 710 patients. Before treatment, 51 patients were HER-2 positive, 287 patients were HER-2 negative, and the results were inconclusive for 75 patients. Of these patients, a pCR in breast and nodes was obtained in 94 patients (14.3%), but this event was threefold more frequent for HER-2-positive patients (23.5%) than for HER-2-negative patients (7%). The overall survival (OS) and disease-free survival (DFS) rates at 10 years were 66.6% and 57.4%, respectively. The DFS rate was, as expected, better for HER-2-negative patients, with HER-2 status assessed before as well as after chemotherapy. A significant difference was found for OS in favor of HER-2-negative patients only with postchemotherapy assessment of HER-2, a fact similar to our previous findings. Finally, there was a tendency toward a higher DFS rate for HER-2-positive patients who achieved a pCR compared with HER-2-positive patients who did not.