Abstract 858: Prognostic markers associated with triple negative breast cancer in Iranian women: a prospective study

Abstract

Abstract Context: Triple negative breast cancer account for 10-26% of all breast cancers, and are associated with worse prognosis. No previous studies have looked at prognostic utility of p53, ki-67 and cathespin D among this group. Objective: To examine the association between protein expression by immunohistochemistry (IHC) of p53, ki-67 and cathespin D and three year disease free (DFS) and overall survival (OS) in women with triple negative breast cancer. Design, Setting, and Patients: Prospective cohort study of 1297 consecutive incident invasive breast carcinoma cases seen between Jan 1998 to June 2008 at Days Hospital in Tehran by a single breast surgeon. Main Outcome Measures: Triple negative breast cancers were defined as tumors lacking the expression of estrogen (ER), progesterone (PR) and being human epidermal factor (HER2) 0 or 1+, as determined by Dako IHC. The odds ratios (OR) of p53, ki-67 and cathespin D expression, recurrence and death among the triple negative cases were determined using logistic regression. Hazard ratios (HR) and 95% confidence interval (CI) were assessed for DFS and OS using Cox proportional regression and adjusting for known prognostic markers. Log-rank test was performed to compare DFS and OS between triple negative cases and other phenotypes, and among the triple negatives as stratified by marker status. Results: Median follow up for the whole cohort was 3.64 years. Triple negative cases constituted 13% (N=167) of the total invasive breast cancer patients (N=1297). The median age of the triple negative cases was forty three years and was not significantly different from the overall cohort. Triple negative cases were more likely to be of advanced grade (p< 0.001) and stage (p <0.001) compared to the overall cohort. Triple negative women had significantly worse DFS (HR=2.64,95%CI:1.50-4.65) and OS (HR=2.37,95% CI:1.05-5.34) after adjustment for known prognostic markers. The odds of expression of Ki67 >15% (the median for Ki67 expression) was significantly higher in the triple negative group compared to the other phenotypes (OR = 2.14, 95%CI: 1.40-3.20). Expression of p53 was also significantly higher in the triple negative group (OR=2.12, 95%CI:1.61-2.77) while cathepsin D was significantly less likely to be expressed (OR=0.70, 95 CI: 0.5-0.97). Among the triple negative group the odds of death was 5.05 (95%CI: 1.35-18.94) for tumors with a Ki67 > 15% and the odds of recurrence was 1.30 (95% CI: 0.94-01.80). Conclusion: Expression of p-53 and Ki67 are increased in triple negative breast cancers, while cathespin D is decreased. Further, among triple negatives high Ki67 is associated with increased mortality. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 858.