Prognostic significance of p53 overexpression in luminal HER2-negative type breast cancer.

Abstract

35 Background: In this study, we evaluated the prognostic significance of p53 overexpression, because it was reported that there was a significant correlation between p53 and resistance to endocrine therapy, and prognosis. Methods: A retrospective analysis was performed using 2,332 primary breast cancer patients who underwent surgery between 2001 and 2010. There were 1,899 cases with luminal subtypes (905 cases: HER2-negative and Ki67 low type; 808 cases: HER2-negative and Ki67 high type; and, 186 cases: HER2-positive type), 155 cases with HER2-enriched subtypes, and 278 cases with triple-negative subtypes. Luminal type was defined as ER-positive cell rates ≥ 1%, regardless of PgR status. The cut-off value of the Ki67 index was 20%. Moreover, tumor size, nodal status and nuclear grade were studied in relation to disease free (DFS) and overall survival (OS) using the Cox proportional hazard model. Results: We found that p53 overexpression was present in 10% of the patients and significantly correlated with larger tumors, younger age, positive nodes, a higher grade, negative ER/PgR, a higher Ki67, and positive HER2. The patients with p53 overexpression had significantly unfavorable prognosis, especially in the patients who only received endocrine therapy. There were 26 cases in the luminal HER2 negative and Ki67 low type group that had p53 overexpression and showed a significantly shorter DFS. In the univariate analysis for DFS, p53, Ki67, tumor size, nuclear grade and nodal status were significant factors in luminal HER2 negative type. In the subsequent multivariate analysis for DFS, the p53 status was one of the most significant factors. Conclusions: The p53 overexpression was a significant prognostic factor in luminal type breast cancer. Therefore, the prognostic evaluation of luminal HER2 negative type breast cancer might be improved using an immunopanel, which includes Ki67 and p53. Moreover, it might isolate the patients who are resistant to endocrine therapy.