Overexpression of p27 protein in human breast cancer correlates with in vitro resistance to doxorubicin and mitomycin C

Background: The cycle regulatory protein p27, an inhibitor of cyclin-depend ent kinase (CDK), has been attributed a role in resistance to cancer chemot herapy. However, the predictive value of p27 for chemosensitivity of breast cancer is still unclear: We therefore analyzed the in vitro chemosensitivi ty to a series of anticancer agents in fresh breast cancer specimens and co rrelated it with the respective expression levels of p27. Materials and Met hods: The expression of p27 protein was examined immunohistochemically in 1 19 patients with primary breast cancer. The in vitro chemosensitivity was a ssessed by the histoculture drug response assay (HDRA) using mitomycin C (M MC), 5-fluorouracil (5-Fu), Doxorubicin (DXR), cisplatin (CDDP) and cycloph osphamide (CPA). Results: Fifty-six (47%) of the 119 patients demonstrated p27 overexpression. The susceptibility of DXR and MMC in tumors with high p 27 expression was significantly higher than that in tumors with low p27 exp ression. Conclusion: Immunohistochemical results regarding p27 might be the ir therapeutically useful as an indicator of response to DXR and/or MMC bas ed adjuvant chemotherapy for breast cancer.