F11 - Prognostic impact of Ki67 for resected early stage pure Invasive Lobular breast Cancer (ILC): cut-off analysis and clinical validation

Abstract

Background: While the prognostic impact of Ki67 has been extensively investigated in invasive ductal carcinoma, despite the absence of a standardized cut-off, its role in ILC has not been fully validated. Thus, the aim of this analysis was to identify the Ki67 with prognostic potential in a multi-center series of patients (pts) affected by early stage pure ILC, investigate its impact in long-term outcome, and validate that in an external pts' cohort. Methods: Clinical-pathological data of consecutive pts affected by pure ILC, undergone surgery at 3 institutions (Verona and Padova as training set [TS] and Roma as validation set [VS]), were correlated with overall survival and disease-free survival (OS/DFS) using a Cox model. The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate the appropriate cut-off. Kaplan-Meier curves were compared with Log-Rank analysis. Results: Overall data from 679 pts (TS: 457, VS: 222) were gathered (median age 61 years [yrs] and 59 yrs) with a median follow-up of 75 (TS) and 71 (VS) months. In the TS, the 5-/10-yrs OS and DFS were 91.8%/81.7% and 82.5%/71.4%, respectively. The maximally selected Log-Rank statistics analysis identified 4% as optimal Ki67 cut-off for OS in the TS. At the multivariate analysis for the TS, Ki67 (HR 2.28, 95% Confidence Interval [CI] 1.0-5.19, p = 0.05), ECOG Performance Status (PS) (HR 3.27, 95% CI 1.49-7.18, p = 0.003), lymph-node status (HR 2.96, 95% CI 1.53-5.74, p = 0.001), and tumor-size according to TNM (HR 2.6, 95% CI 1.31-5.13, p = 0.006) were independent predictors for OS. PS (HR 3.73, 95% CI 1.50-9.30, p = 0.005) and lymph-node status (HR 3.75, 95% CI 1.70-8.26, p = 0.001) were independent predictors for DFS. No difference in OS between the TS and VS according to Ki67 were found, as shown in the table.Tabled 1OSTSVSLog-RankKi67 ≤ 4%5-yrs100%96.9%p = 0.3810-yrs90.1%81.8%Ki67 > 4%5-yrs89.9%83.0%p = 0.3110-yrs77.2%75.6% Open table in a new tab Conclusions: Despite the retrospective and exploratory nature of the study, a very low cutoff of Ki67 (4%) significantly discriminates the prognosis of patients with ILC.