Titration of Serum p53 Antibodies Predicts Pathological Response in Women with Operable Early Stage Breast Cancer Receiving Preoperative Sequential FEC and Docetaxel Chemotherapy.

Abstract

Abstract Background: In breast cancer, emerging dates demonstrate that p53 mutation is associated with response to preoperative chemotherapy, indicating that p53 mutation may be a predictive factor for response to preoperative chemotherapy. The accumulation of mutant p53 protein has been found to induce the formation of serum p53 IgG antibodies in breast cancer patients. A highly specific quantitative enzyme-linked immunosorbent assay (ELISA) kit has been developed to detect p53 antibody titers. However, whether this titration of serum p53 antibody reflects response to preoperative chemotherapy is unknown. The aim of this study was to evaluate the clinical implication of serum p53 antibody titers as a predictive factor for preoperative chemotherapy in breast cancer.Patinets and Methods: In this study, we analyzed 103 women with operable early stage breast cancer treated by preoperative chemotherapy and definitive curative surgery. Patients received four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 q3w) followed by four cycles of docetaxel (75 mg/m2 q3w). The pretreatment serum samples were used to determine the p53 antibody titers. The test's cut-off value was determined to be 1.3 U/ml based on reference distribution in healthy control individuals.Results: Twenty-three of 103 patients (22.3%) were positive for serum p53 antibody. The frequency of pathological complete response (pCR) was significantly higher in cases with positive for p53 antibody than in patients with negative for p53 antibody (9/23 or 39% vs. 15/80 or 23%; p=0.04). According to intrinsic subtypes, the tendency was most emphasized in cases with HER2-positive cases (6/9 or 67% vs. 8/25 or 32%). Interestingly, among 8 patients with high p53 antibody titers (>100 IU/ml) 7 patients experienced pCR and remaining one patients showed only foci invading areas in primary tumor and complete remission in axillary lymph node metastasis, suggesting that the value of p53 antibody titers may more precisely predict response to preoperative chemotherapy.Conclusion: p53 mutation analysis using titration of serum p53 antibody is useful predictive test for response to preoperative chemotherapy in patients with breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2038.