P53 expression predicts poorer survival in African-American women with breast cancer

Abstract

9635 Background: Outcome disparities for African-American (AA) women with breast cancer, including late stage presentation & poorer survival, may in part be due to biologically aggressive tumors. We hypothesized that survival would be worse for AA women with breast tumors which demonstrate abnormal p53 tumor suppressor gene function. Methods: Tumors from 188 consecutive AAs were evaluated for abnormal nuclear accumulation of p53 protein with IHC, using monoclonal antibodies DO-7 & Pab 1801 on paraffin embedded tissue, at the SHCC MBCCOP, in Chicago. Staining was scored on the UK Receptor Group, 0–8 system, with ≥2 as positive, & slides were read by 2 blinded pathologists. Disease-free survival (DFS), distant-disease free survival (DDFS), & overall survival (OS) were computed by the Kaplan-Meier method & correlated with p53 expression. Univariate analyses were performed with the use of a two-sided log-rank test & multivariate analysis was performed with the use of the Cox proportional-hazards model. Results: A total of 72 cases (39.6%) were positive with D07 IHC, 47 cases (27%) were positive with 1801 IHC, & 42 cases (30.2%) were positive for both D07 & 1801 IHC. The mean follow-up was 48 months & young age, high AJCC stage, high tumor grade & negative ER status, were all significantly correlated with p53 expression & poorer survival. p53 expression with 1801 IHC was significantly correlated with DFS, DDFS, & OS. For DFS, 44 events occurred, Hazard Ratio (HR)=2.63, 95% Confidence Interval (95% CI)=1.43–4.85, p=0.002; for DDFS, 34 events occurred, HR=2.68, 95% CI=1.33–5.41, p=0.006; and for OS, 25 events occurred, HR=2.93, 95% CI=1.31–6.55, p=0.009. Multivariate analysis demonstrated that independent predictors for DFS were p53 expression (HR=2.04, 95% CI=1.08–3.85, p=0.027), stage (HR=3.0, 95% CI=1.57–5.73, p=0.0008) & PR status (HR=0.46, 95% CI=0.23–0.95, p=0.036); for DDFS, p53 expression (HR=2.46, 95% CI=1.21–5.0, p=0.012) & stage (HR=3.26, 95% CI=1.58–6.71, p=0.001); and for OS, p53 expression (HR=2.69, 95% CI=1.19–6.10, p=0.017) & stage (HR=2.75, 95% CI=1.22–6.23, p=0.014). Conclusions: Abnormal nuclear accumulation of p53 protein independently predicts poorer survival & agressive biology in AA women with breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Avon Foundation, NCI