Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer
BackgroundThe aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery.MethodsClinical pathological data were correlated with disease free and overall survival (DFS/OS) The maximally selected Log Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67.ResultsAt a median follow up of 67 months, 10 years DFS and OS of 405 patients were 67.8 and 79.8 respectively. Standardized Log Rank statistics identified 2 optimal cut offs (6 and 21 10 years DFS and OS were 75.1, 66.5, and 30.2 (p 0.01) and 84.3, 76.4 and 59 (p 0.003) for patients with a Ki67 6 between 6 and 21 and >21 respectively. Ki67 and lymph node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS) Ki67 highly replicated at the internal cross validation analysis (DFS 85 OS 100 The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology.ConclusionsDespite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC.
Journal of experimental clinical cancer research CR