Prognostic (Px) significance of Ki67 before and after neoadjuvant chemotherapy (CT) in early breast cancer

Abstract

573 Background: High levels of the proliferation marker Ki67 are associated with a higher response rate to CT but poorer long-term outcome. The Px significance of Ki67 before CT and at surgical excision was compared. Methods: 103 patients treated with CT with pre- and post- (excision) CT tissue and a further 181 with only excision tissue available were identified, 37 and 76 of these respectively were ER+ and also received tamoxifen. The following factors were considered pre-CT and at excision (where relevant) for their relationship with relapse-free (RFS) and overall (OS) survival: ER, PR, HER2, grade, Ki67, histological type, vascular invasion, age/menses, T and N stage, pre-therapy operability, clinical response, CT regimen, type of surgery, adjuvant therapy, pathological tumour size and nodal involvement. Results: In the paired cohort univariate analysis of RFS the following factors were associated with poorer Px (a) pre-CT: ER- (p=0.003); increasing T stage (p<0.001), N stage (p=0.002) and Ki67 (p<0.001); (b) at excision: increasing grade (p=0.01), tumour size (p=0.02), nodal status (p<0.001) and Ki67 (p<0.001); no adjuvant endocrine therapy (p<0.001). On multivariate analysis only excision Ki67 (p<0.001) was significant although there was a suggestion pre-therapy Ki67 was important (p<0.10). On univariate analysis of OS the following factors associated with poorer Px (a) pre-CT: ER- (p=0.006); increasing T stage (p<0.001) and Ki67 (p<0.001); (b) at excision: increasing grade (p=0.04), tumour size (p=0.005), nodal status (p<0.03) and Ki67 (p<0.001); no adjuvant endocrine therapy (p=0.001). On multivariate analysis both pre-CT and excision Ki67 were significant independent predictors but the latter was more highly significant. (p<0.02 + p<0.0001, respectively) Assessing the combined group of 284 patients, after 5 years the highest and lowest tertiles of excision Ki67 had strikingly different Px: RFS 36% and 73%; OS 50% and 85%, respectively. Conclusions: Ki67 after CT is a strong predictor of long-term outcome. The greater significance of Ki67 in the excision sample may be due to this identifying patients in whom residual highly proliferative disease remains after CT. No significant financial relationships to disclose.