Abstract P4-11-43: Ki-67 and p53 are useful factors to predict long term survival in low-risk luminal A breast cancer patients

Abstract

Abstract Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A (ki-67-, p53-)), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. Table 1. Factors associated with overall survival in luminal A subtype breast cancer patients (N=3918). Univariable Multivariable* Factors HRP-value95% CI for HRHRP-value95% CI for HRBreast surgery TM- (ref.)- (ref.)- (ref.) BCS0.4430.03180.211-0.932 Presence of LVI No- (ref.)- (ref.)- (ref.) Yes4.783<0.00012.163-10.578 RM Positive2.7260.32690.367-20.244 Negative- (ref.)- (ref.)- (ref.) NG 1&2- (ref.)- (ref.)- (ref.) 33.7930.00041.806-7.969 AJCC Stage 1- (ref.)- (ref.)- (ref.)- (ref.)- (ref.)- (ref.) 22.2830.16970.703-7.4161.7840.33800.546-5.833 312.967<0.00014.303-39.0839.912<0.00013.265-30.096Ki-67 Positive4.2940.00321.631-11.3032.5870.06030.960-6.971 Negative- (ref.)- (ref.)- (ref.)- (ref.)- (ref.)- (ref.)p53 Positive6.107<0.00012.905-12.8374.494<0.00012.105-9.594 Negative- (ref.)- (ref.)- (ref.)- (ref.)- (ref.)- (ref.)BCS, breast-conserving surgery; LVI, lymphovascular invasion; NG, nuclear grade; RM, resection margin; TM, total mastectomy; NG, LVI and total mastectomy were not significant in multivariable Cox analysis;* Cox-proportional hazard regression model. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility. Citation Format: Ha Woo Yi, Se Kyung Lee, Soo Youn Bae, Jun Ho Lee, Hyun-Chul Lee, Won Ho Kil, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam. Ki-67 and p53 are useful factors to predict long term survival in low-risk luminal A breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-43.