Downregulation of the cyclin-dependent kinase inhibitor p27kip1 might correlate with poor disease-free and overall survival in inflammatory breast cancer.
OBJECTIVE
The objective of this study was to evaluate whether p27kip1 downregulation is a prognostic factor in patients with inflammatory breast carcinoma (IBC).


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 p27kip1 was evaluated by indirect immunoperoxidase procedure. The p27kip1 was considered downregulated if nuclear staining was present in < 50% of the neoplastic cells.


RESULTS
Thirty-two patients (84%) had p27kip1-downregulated tumors, and 6 patients (17%) had p27kip1-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 p27kip1-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).


CONCLUSIONS
The p27kip1 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.
Gonzalez-Angulo
Ana Maria
AM
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77230-1439, USA. agonzalez@mdanderson.org
Guarneri
Valentina
V
Gong
Yun
Y
Cristofanilli
Massimo
M
Morales-Vasquez
Flavia
F
Sneige
Nour
N
Hortobagyi
Gabriel N
GN
Esteva
Francisco J
FJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008408:Mastectomy; D008413:Mastitis / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27