C-kit expression in high-risk breast cancer subgroup treated with high-dose or conventional dose-dense chemotherapy.

Abstract

The proto-oncogene c-kit is known to be expressed in poorly differentiated breast cancer. In this study, we retrospectively evaluated the prognostic and predictive impact of c-kit in a high risk subgroup of breast cancer patients (>9 axillary node metastases) who received high-dose (HDCT) or dose-dense (DDCT) conventional chemotherapy and correlated these findings with the expression of the basal-type markers CK5 and CK 17, estrogen (ER) and progesterone (PR) receptor, Her-2/neu and MIB 1. C-kit, CK5, CK17, ER, PR, Her-2/neu and MIBI expression was evaluated immunohistochemically using tissue microarrays containing breast cancer samples from 236 patients who were randomized to the WSG AM01 trial (median follow-up of 60 months). There was a significant overall survival (OS) benefit for patients receiving HDCT compared to DDCT (p = 0.027). C-KIT expression was found in 12 % of all breast cancers and correlated with a poorer OS in multivariate analysis (p = 0.051). Furthermore, c-kit correlated with high grade (p = 0.019), CK5- and CK17-positivity (p <0.0001 and p = 0.001, respectively) and ER- and PR-negativity (p = 0.04 and p = 0.008, respectively). In contrast to CK5 and CK17, patients with c-kit positive breast cancers revealed no benefit from high-dose chemotherapy. These findings underline that c-kit expression represents an independent negative prognostic marker in high-risk breast cancer. Correlation with CK5 +/CK17+ and ER-/PR-suggests that c-kit positive carcinomas are at least partly of basal-type.