Downregulation of the cyclin-dependent kinase inhibitor p27^kip1 might correlate with poor disease-free and overall survival in inflammatory breast cancer

Purpose: The objective of this study was to evaluate whether p27^kip1 downregulation is a prognostic factor in patients with inflammatory breast carcinoma (IBC). Patients and Methods: Fifty-eight patients with IBC were treated between January 1994 and July 2002. Median age was 49 years. Thirty-eight patients had baseline biopsy specimens. Patients received preoperative chemotherapy with FAC (5-fluorouracil/doxorubicin/cyclophosphamide; 34%) or FAC followed by a taxane (66%). All patients underwent mastectomies. All patients received radiation therapy and hormonal treatment when indicated. Expression level of p27^kip1 was evaluated by indirect immunoperoxidase procedure. The p27^kip1 was considered downregulated if nuclear staining was present in < 50% of the neoplastic cells. Results: Thirty-two patients (84%) had p27^kip1-downregulated tumors, and 6 patients (17%) had p27^kip1-normal tumors. Six patients (16%) exhibited a pathologic complete response. At a median follow-up of 43 months, 25 recurrences (66%) and 27 deaths (71%) occurred. Patients with p27^kip1-downregulated tumors had fewer pathologic complete responses (9% vs. 50%; P = 0.03) and had lower 4-year recurrence-free survival (23% vs. 83%; P = 0.03) and overall survival rates (36% vs. 83%; P = 0.01). Conclusion: The p27^kip1 deregulation manifested by low protein cellular concentration might represent an adverse prognostic marker in IBC and could provide a valuable tool for selecting treatment for this aggressive disease.