Molecular markers of therapeutic resistance in breast cancer.

Resistance to chemotherapy and endocrine therapy is a serious obstacle in the treatment of breast cancer. Highly specific biomarkers for predicting therapeutic resistance have not yet been identified. In this study, the amounts of aldehyde dehydrogenase 1, cleaved caspase 3, cyclooxygenase 2, phosphorylated Akt, Ki-67, and H2AX proteins were measured by immunohistochemical staining in 113 breast cancer tissues, and their predictive ability for therapeutic resistance was investigated. The patients were receiving chemotherapy (n = 30), endocrine therapy (n = 22), or combined chemotherapy and endocrine therapy (n = 61). Expression of aldehyde dehydrogenase 1, cleaved caspase 3, and cyclooxygenase 2 correlated significantly with a higher relapse rate (P < .05 or P < .01) and shorter survival (P < .01 or P < .001) in triple-negative patients receiving chemotherapy. In addition, cyclooxygenase 2 expression was an independent predictor of a poor prognosis (P < .05). On the other hand, aldehyde dehydrogenase 1 expression correlated significantly with shorter survival in patients receiving combined therapy (P < .01) but showed no association with relapse. No correlation was observed between Ki-67, phosphorylated Akt, and H2AX expression and survival or relapse in any group of patients. These data suggest that aldehyde dehydrogenase 1, cleaved caspase 3, and cyclooxygenase 2 are useful markers for therapeutic resistance in breast cancer.