Abstract PD07-04: Predicting Outcome with Ki67 in Primary Breast Cancer in the Neoadjuvant Setting

Abstract

Background: The proliferation antigen Ki67 has been shown to be a reliable predictive marker of treatment efficacy in the neoadjuvant treatment of breast cancer but its prognostic significance remains uncertain. This study assesses Ki67 before and after neoadjuvant chemotherapy (NAC) in relation to long-term outcome. Methods: 117 patients with primary breast cancer due to undergo NAC were studied (median age 48 years, range 25-78; T2-4, N0-3, M0) and information gathered from a prospectively maintained database. Immunohistochemically derived Ki67 expression was obtained from pretreatment core biopsy and surgical specimens. Their relationship to DFS and OS was analyzed along with known prognostic variables (age, ER/PR/HER2 status, clinical and pathologic T and N stage, grade), NAC regimen, response and adjuvant treatment. Survival curves were estimated using the Kaplan-Meier method and a log-rank test used to determine significance using a two-tailed p-value of 0.05. A multivariate Cox proportional hazards regression model performed in a stepwise fashion was used to determine the prognostic value of each signifcant variable. Results: 84 patients with matched biopsy and surgical samples were assessable for pre and post NAC Ki67 levels. The majority (90%) received anthracycline based NAC (median number of cycles 6, range 2-6). On univariate analysis, the only significant pretreatment predictive factor for shorter DFS was higher clinical nodal stage (cN) (P<0.001). Posttreatment variables that predicted for worse DFS were: Ki67 at surgery (HR 1.52, p=0.048), pathologic nodal stage (pN) (p=0.001) and grade (p=0.013). On multivariate analysis, pN was the most powerful predictor for DFS (chi-squared test 19.8, 3 df, P<0.001). Univariate analysis of pretherapy factors for OS revealed that Ki67 at biopsy (HR 2.06, p=0.039), cN (HR 4.44, P<0.001) and PR positivity (HR 0.41, p=0.012) were significant. Significant posttreatment variables for OS were Ki67 at surgery (HR 2.01, p=0.006), pN (p=0.001), and grade (p=0.009). PR status and pN remained important predictors of OS on multivariate analyses. Conclusions: The expression of Ki67 is a widely accepted marker of cellular proliferation in breast cancer. Ki67 levels after NAC were a better predictor for long-term outcome than pretherapy Ki67, although nodal status appears to be the most powerful determinant overall. High Ki67 levels post NAC may identify patients with poorer outcomes who are candidates for further systemic therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-04.