Neoadjuvant Chemotherapy In The Locally Advanced 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 clinical and pathologic response and toxicity of vinorelbine(N) and epirubicin(E) as the neoadjuvant chemotherapy in the treatment of locally advanced breast cancer(LABC). To identify predictive markers that may effectively predict the clinical and pathologic response of the neoadjuvant chemotherapy. To have a preliminary investigation of the relationship between the changing of biomarkers expression induced by neoadjuvant chemotherapy and response of the neoadjuvant chemotherapy.Patients and Methods: From September 2001 to December, 2003, 102 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine(N), 25 mg/m2 (days 1 and 8) and epirubicin(E), 60 mg/m2 (days 1) 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 and postoperative tumor tissue. The relationship between the response and the expression of biomarkers in the preneoadjuvant chemotherapy core specimens and characteristic of patients were analyzed to find the predictive factors of neoadjuvant chemotherapy. Comparisons of expression of biomarkers before and after neoadjuvant chemotherapy in responding and non-responding group in order to have a investigation of biological mechanism of neoadjuvant chemotherapy. Results: The clinical objective response was 81.3% (23.5%(24/102) CR and 57.8%(59/102) PR). Pathological complete response was found in 19 cases (18.6%). 11 cases (25%) who have positive FNA result in the axillary lymphnode before chemotherapy show negative result in the surgery specimen. The most common toxicities are neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3-4 was reported in 70.6% but there was no serious septemia and toxic deaths. Patients with Neu+(p=0.019),Bax- (p=0.047)and ki-67≥12%(p=0.013)were more likely to have a pathological complete response to the NE neoadjuvant chemotherapy. Changes in all the biomarkers after neoadjuvant chemotherapy were observed. ER, PR and p53 positive tumor more likely to be changed into negative expression after neoadjuvant chemotherapy than that of negative changed into positive (55.56%-69.4% vs. 19%-20%). But MDR and MRP negative tumor may change more frequent into positive than positive to negative (74.2%-75% vs. 23.5%-33.3%). The pathological complete response rate was higher in ki-67 overexpression group. The ki-67 expression down-regulation significantly higher in residual carcinoma in situ than that still had invasive carcinoma after neoadjuvant chemotherapy(p=0.045)Conclusion: The combination of Vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC. The biomarkers of Neu, Bax and ki-67 in locally advanced breast cancer were independent predictive factors of pathological complete response for NE neoadjuvant chemotherapy. The neoadjuvant chemotherapy can modulate the expression of tumor biomarkers. Ki-67 indices were reduced in residual tumor tissues after chemotherapy and the reduction degree in the residual carcinoma in situ was significantly higher than that of residual invasive carcinoma. ER, PR and p53 down-regulated while MDR and MRP up-regulated afte...