Preliminary Study Of Predictive Biological Markers For Response Of Neoadjuvant Chemotherapy In Breast Cancer

Background: Neoadjuvant chemotherapy(NAC) has been widely accepted as the standard management of locally advanced breast cancer in recent years. Patients who gained pathologic complete response (pCR) after neoadjuvant chemotherapy may have improved long term survival. It is very important to improve the efficacy of neoadjuvant in the treatment of locally advanced breast cancer. In addition, the identification of reliable predictive markers for the response of neoadjuvant chemotherapy and better understanding of the biologic mechanism of neoadjuvant chemotherapy will greatly help to make individual treatment scheme in the management of locally advanced breast cancer.Purpose: To evaluate the predictive value of biological markers for neoadjuvant chemotherapy in the treatment of locally advanced breast cancer .Patients and Methods: From June 2004 to June 2006, 62 patients with LABC [barring IBC (inflammatory breast cancer )]were treated with CEF (cyclophosphamide , epirubicin , 5-fluorouracil ; days 1 and 8)or ET (epirubicin, Pacliptxel ;days 1 ) chemotherapy before operation. They was administered every 3 weeks for three cycles before local treatment. Core needle biopsy samples were obtained before the initiation of neoadjuvant chemotherapy. Biological markers were evaluated by IHC in the preneoadjuvant chemotherapy biopsy specimens . The relationship between the response and the expression of biomarkers in the preneoadjuvant chemotherapy core specimens of patients were analyzed to find the predictive factors of neoadjuvant chemotherapy.Result: The reacting rate of CEF was 61.8%, ET was 85.7%;the clinical complete remission rate of CEF was 11.8%, ET was 21.4%; the clinical partial remission rate of CEF was 50.0%, ET was 64.3%;and the pathological complete remission rate of CEF was 8.8%, ET was 14.3%. The reacting rate was significant difference between the CEF and ET groups( P<0.05), but there were no significant differences between the CEF and ET groups in the clinical or pathological complete remission rate ( P=0.326, P=691 ). The most common toxicities are neutropenia, alopecia and nausea/vomiting, but there were no toxic deaths. In univariate analysis, patients'tumor size <5 cm showed significantly higher reacting rate than those≥5 cm ( P<0.05).Multivariate analysis showed the same result ( P=0.015 ). p53-negative, Ki-67-positive , BCRP-negative tumors showed significantly higher reacting rate than that were p53- positive,Ki-67- negative, BCRP- positive in CEF groups( P < 0.05). Multivariate analysis :the expression of Ki-67(P=0.041) or BCRP(P=0.049) showed independent correlation with the reaching rate.Conclusion: There was a significant difference between the reaching rate of CEF and ET groups, the latter maight be higher than the former. The tumor size and the biomarkers of Ki-67 and BCRP in locally advanced breast cancer were independent predictive factors of reacting rate for CEF and ET neoadjuvant chemotherapy. Otherwise, patients with Her-2- negative might benefit more from ET neoadjuvant chemotherapy.