O1-15-2TP53 SIGNATURE PREDICTS THE EFFICACY OF NEOADJUVANT CHEMOTHERAPY (NAC) OF BREAST CANCERS

Abstract Background: We have reported that status of the TP53 mutation is predictable by expression profile of 33 genes (TP53 signature) in breast cancer and that the TP53 signature can predict overall survival and recurrent free survival of early breast cancer (Cancer Sci. 99: 324-32, 2008). The aim of this study is to determine whether the TP53 signature can also predict both the efficacy of NAC and the recurrence after surgery in breast cancer. Methods: An NAC cohort (E-GEOD-25066) that contains 508 patients with HER2 negative breast cancer is used. Among the genes previously used TP53 signature, 20 up-regulated and 5 down-regulated genes in breast cancer with TP53 mutation were selected and the TP53 status was determined by the ratio of the sum of expression values of 20 up-regulated genes to that of the 5 down-regulated genes. If the ratio (down / up) was less than 0.325, the tumor was determined as aTP53 mutant. If it was greater than or equal to 0.325, the tumor was determined aTP53 wild. Results: Fifty percent (255 of 508) of tumors was determined as a TP53 mutant. The pathological CR (pCR) rate is significantly higher in TP53 mutant tumor than in TP53 wild-type tumor (34.7% vs 5.4%). In Stage I and II patients (n = 280), recurrence free survival (RFS) was significantly better in patients with TP53 wild type tumor (P = 0.0018). Patients with TP53 mutant tumor not leading to pCR (mt / non-pCR) showed significantly worse RFS than the other patients (P Conclusions: TP53 signature has the ability to predict the efficacy of NAC and recurrence after surgery in breast cancer. The TP53 signature was especially useful to predict the recurrence in combination with pCR status. Our data suggests that patients with TP53 mutant tumor not leading to pCR after NAC may need adjuvant chemotherapy after surgery to improve prognosis of these patients.