Predictive Biological Markers for Response of Invasive Breast Cancer to Anthracycline / Cyclophosphamide-based Primary (Radio-)Chemotherapy

Abstract

Background: The role of biological markers for the prediction of neoadjuvant chemotherapy and radio-chemotherapy may be evaluated using pathological complete response [pCR] in patients with invasive breast cancer. Materials and Methods: To investigate this, pre-treatment biopsies from 517 patients with locally advanced breast cancer were analyzed for expression of estrogen receptor [ER], progesterone receptor [PgR], Her-2/neu, epidermal growth factor receptor [EGF-R], p53, Bcl-2 and MIB-1 by immunohistochemistry [IHC], and these data were compared to the pathological response after preoperative epirubicine/cyclophosphamide [EC] chemotherapy (+/- radiotherapy). Results: pCR was more frequent (28.3%, 56/198) in tumors that received radio-chemotherapy compared to chemotherapy alone (11.9%, 38/319, p<0.0001). Patients with high grading, lower ER, PgR, Bcl-2 or a higher proliferation had a significantly greater benefit from chemotherapy. The overexpressions of Her2/neu or EGF-R were weakly correlated to pCR, while p53 staining did not have any predictive value. Younger patients, with negative PgR and high proliferation index, had the highest benefit from EC therapy (56% pCR). The different multivariate indices of binary regression, PLS-DA and SIMCA, had similar predictive quality and were slightly superior to univariate factors. Conclusion: This study emphasizes the value of traditional biological markers and Bcl-2 for use in the individual selection of a primary therapy regimen.