P53 EXPRESSION IS A SIGNIFICANT PREDICTOR OF RESPONSE AND PROGNOSIS IN STAGE II-III BREAST CANCER PATIENTS TREATED WITH PREOPERATIVE CHEMOTHERAPY

Introduction and Aims: p53 protein is a mediator of the cellular response to DNA damage. Mutation in p53 genes has been reported in breast cancer (BC) , and has been suggested as potential marker of chemoresistance. Aim of this study is to evaluate the predictive and/or prognostic role of p53 expression in a consecutive series of BC patients (pts) treated with preoperative chemotherapy (PCT). Patients and Methods: pts with stage II-III BC were included. The expression of p53 was evaluated by IHC on the diagnostic core biopsy, (Cellmar D07Ab, cut off: staining in ³ 10% of cells). Pts received 4-6 courses of PCT before surgery. Pathologic complete response (pCR) was defined as complete disappearance of invasive tumor in breast and axillary nodes. The association between biomarkers and pCR was assessed by Pearson chi square test. Survival was estimated with the Kaplan-Meier method. Results: 155 BC pts were included. Median age was 52 yrs (range: 29-76). Clinical stage at diagnosis: II A-B in 80% of the pts, IIIA-B in 20% of the pts. The majority of the pts (72%) had ER+ tumors; 22% of the pts were HER2 +. 68 pts (44%) showed p53 overexpression (mean expression 24%: range 0-99%). p53 overexpressing tumors were significantly less ER +(63% vs 79%, p=0.02). p53 expression was also positively correlated with higher levels of ki67 (87 vs 70%, p=0.012). PCT consisted of anthracycline-based regimens in 40 pts; anthra/taxanes combinations in 110 pts; a taxane regimen in 4 cases. After PCT, 43% of the pts underwent conservative surgery. A pCR was observed in 5.3% of the pts. The probability of pCR was significantly higher in case of p53 overexpression (10.8% vs 1%, p=0.009), ER negativity (11.6% vs 2.8%, p=0.028), HER2 positivity (12 vs 3.4%, p=0.04), and nuclear grade 3 (9% vs 0, p=0.02). The overall 5-yr DFS and OS were 70% and 85%. The 5-yr DFS in case of p53 <10% was 82% vs 55% in p53 >/= 10% (p=0.0038). The 5-yr OS in case of p53 <10% was 99% vs 67% in p53 >/= 10% (p<0.0001). Conclusions: the expression of p53 is significantly associated with a higher probability of achieving a pCR to PCT including anthracyclines +/- taxanes. However, inspite of the greater chemosensitivity, in our study p53 overexpression is a negative prognostic parameter. The role of p53 in patients receiving PCT warrants further studies. Supported in part by a Ministry of Health Research grant (Progetti Integrati Oncologia # 04/07)