Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identif y those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior, p27k ip1 is an important inhibitor of the cell cycle that acts by binding and in activating cyclin-dependent kinases (CDKs). The aim of this study was to de termine the prognostic value of loss of p27 protein in invasive breast canc er. We performed an immunohistochemical study of 147 patients with T1 and T 2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis com paring tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor , low or absent p27kip1 is a strong predictor of reduced disease-free survi val. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival th an either marker alone. This simple, reliable and inexpensive assay, partic ularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer eval uation to better identify high risk patients.