Loss of p27(kip1) expression is associated with poor prognosis in patients with taxane-treated breast cancer

Abstract

Purpose: Decreased expression of p27(kip1) and p57(kip2) is considered as a prognostic indicator in patients with breast cancer receiving adjuvant chemotherapy. Previous in vitro studies have reported that reduced expression of p27(kip1) and p57(kip2) is associated with resistance to taxane, which is one of the most effective chemotherapeutic agents. In this study, we investigated the association of low p27(kip1) and p57(kip2) expression with outcomes in patients with breast cancer. Methods: We investigated 226 cases of breast cancer from Kangbuk SMC between 2000 and 2005. Levels of p27(kip1) and p57(kip2) expression were evaluated using immunohistochemical staining of tumor tissue microarray specimens. The relationships between the expression levels of the markers and patients' outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazard model. Results: Low p57(kip2) expression was only associated with negative progesterone receptor status (p = 0.034), whereas p27(kip1) expression was associated with poor prognosis of patients receiving adjuvant chemotherapy (p = 0.005). More detailed analysis revealed that low p27(kip1) expression affects the overall survival rate of patients receiving adjuvant chemotherapy including taxane (p = 0.026), but not that of patients receiving chemotherapy without taxane. Conclusions: Low p27(kip1) expression may be useful to predict overall survival in patients with breast cancer who are treated with taxane. Evaluation of p27(kip1) expression may provide further prognostic information beyond traditional prognostic biomarkers and an understanding of the mechanisms that impart resistance against chemotherapy.