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Chemotherapy Response of Breast Cancer Depends on HER-2 Status and Anthracycline Dose Intensity in the Neoadjuvant Setting

Departments of Medical Oncology [T. P., C. B., A. E., R. M., P. H.], Pathology [J-P. G.], and Surgery [J-F. R.], Centre de Lutte Contre le Cancer Paul Strauss, 67085 Strasbourg Cedex, France

We evaluated the predictive value of a tumor’s HER-2 status for chemotherapy response in the neoadjuvant setting and the effect of anthracycline dose intensity on this predictive value. HER-2 status was evaluated by immunochemistry on microbiopsy before neoadjuvant chemotherapy (monoclonal antibody CB-11; Novocastra) in 39 patients (group A) treated with FEC50 (500 mg/m² 5-fluorouracil, 50 mg/m² epirubicin, and 500 mg/m² cyclophosphamide) and 40 patients (group B) treated with FEC100 (500 mg/m² 5-fluorouracil, 100 mg/m² epirubicin, and 500 mg/m² cyclophosphamide). All tumors were stage II or noninflammatory stage III adenocarcinoma. Overall response rate (OR) was evaluated through ultrasound and mammographic measurements. Pathological complete response was evaluated by tumor excision and axillary node resection after six cycles of chemotherapy. Patient and tumor characteristics (age, tumor size, clinical nodal status, SBR grade, hormonal receptor status, and HER-2 expression) were similar in the two groups. In univariate analyses, anthracycline dose was the only factor predictive of response (OR = 61.5% with FEC50; OR = 82.5% with FEC100; P = 0.038). When anthracycline dose was correlated with HER-2 status, an OR of 73.9% was demonstrated in HER-2- tumors (tumors without HER-2 overexpression), and an OR of 12.5% was demonstrated in HER-2+ tumors (tumors with HER-2 with overexpression) in group A. In group B, an OR of 69.5% was demonstrated in HER-2- tumors, and an OR of 100% was demonstrated in HER-2+ tumors. There was no difference in OR for HER-2- tumors treated with FEC50 or FEC100 (P = 0.74). On the other hand, erbB-2+ tumors treated with FEC100 had a significantly better OR than HER-2+ tumors treated with FEC50 (P = 0.0003). In a multivariate analysis, the most powerful predictive factor of OR was a conditional variable associating anthracycline dose with HER-2 status. Low-dose anthracycline and HER-2+ predicted a poor OR, low- or high-dose anthracycline and HER-2- predicted an intermediate OR, and high-dose anthracycline and HER-2+ predicted a high OR. Our results merit additional studies, given the possibility for choosing anthracycline dose according to a tumor’s HER-2 status.

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