P53 expression and clinical outcomes in untreated and treated breast cancer patients after long-term follow-up.

Abstract

e14745 Background: p53 alteration represents one of the hallmarks of malignant transformation. However, its role on treatment outcome remains controversial and is unknown in untreated patients in breast cancer. This study aims to evaluate p53 expression in association with clinical outcomes in untreated patients relative to those undergoing homogeneous therapy. Methods: p53 protein was examined by immunohistochemistry in 956 patients with stage I, II and III breast cancer. Overall survival (OS) and relapse-free survival (RFS) between p53-positive and -negative tumors in chemotherapy, radiation or endocrine therapy alone and no treatment groups were estimated by Kaplan-Meier method. OS and RFS were further assessed by multivariable Cox model that incorporates p53, age, tumor size and grade, estrogen receptor, and HER2 in specific treatment group(s). Results: p53 expression was detected in 22.7% of breast cancer. Median follow-up time was 115.5 months, with a range of 5 to 282 months. Expression of p53 was associated with younger age at diagnosis, higher tumor grade, ER/PR negativity, and HER2 positivity ( P< 0.001). Without any treatment including systemic and radiation therapy (n = 227), OS and RFS curves were overlapped from the beginning until the end of follow-up between p53-positive and -negative patients, respectively. In contrast, p53 was significantly associated with worse OS and RFS with univariate analysis and multivariate statistics of OS (HR 4.07, 95% CI 1.95-8.50; P< 0.001) and risk of relapse (HR 2.23, 95% CI 1.11-4.48; P= 0.025) by endocrine therapy alone (n = 130). Moreover, apparent trends for p53 toward unfavorable OS and RFS were observed in those undergoing homogeneous radiation therapy and chemotherapy, only within 150 months of follow-up. Conclusions: p53 is not associated with clinical outcomes in the absence of conventional therapy, and independently predicts worse survival and increased risk of recurrence after endocrine therapy.