© The Author 2006. Published by Oxford University Press.
ARTICLE |
p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy
Affiliations of authors: Divisions of Human Biology and Public Health Sciences (PLP, MGL, XPY, ED) and Basic Sciences (JMR), Fred Hutchinson Cancer, Research Center, Seattle, WA; Departments of Pathology (PLP),Biostatistics (WEB), and Oncology (RBL), University of Washington, Seattle, WA; Cancer Rsearch and Biostatistics, Southwest Oncology Group Statistical Center, Seattle, WA (WEB); Department of Pathology, University of Texas Health Science Center, San Antonio, TX (ITY); Department of Medicine and Pathology, Indiana University, Indianapolis, IN (GWS); Department of Hematology and Oncology, Ohio State University, Columbus, OH (CLS); Department of Oncology, Mayo Clinic, Rochester, MN (JNI); Department of Medicine, University of California, Los Angeles, CA (CMH); Department of Hematology and Oncology, Loyola University, Chicago, IL (KSA); Department of Medicine, University of Michigan, Ann Arbor, MI (DFH)
Correspondence to: Peggy L. Porter, MD, Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109 (e-mail: pporter{at}fhcrc.org).
Background: Abnormal expression of the cell cycle regulatory proteins p27Kip1 (p27) and cyclin E may be associated with breast cancer survival and relapse. We studied these markers in a clinical trial setting with patients with breast cancer treated by a uniform drug regimen so that treatment was not associated with variability in outcome. Methods: We used tissue microarrays to evaluate the expression of p27 and cyclin E proteins by immunohistochemistry in tumor tissue from 2123 (68%) of 3122 patients with moderate-risk primary breast cancer who were enrolled in Southwest Oncology Group–Intergroup Trial S9313, in which patients were assigned to receive doxorubicin and cyclophosphamide administered concurrently (n = 1595) or sequentially (n = 1527). Disease-free and overall survival were equivalent in the two arms. Expression of the proteins was rated on a scale of 1–7, and the median value was used as the cut point. Log-rank tests and Cox regression analyses were used to assess associations with survival. Overall survival was defined as time to death from all causes; disease-free survival was defined as time to recurrence or death. All P values were from two-sided statistical tests. Results: Lower p27 expression was associated with worse overall survival (unadjusted hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.21 to 1.86) and disease-free survival (unadjusted HR = 1.31, 95% CI = 1.10 to 1.57) than higher p27 expression. Among hormone receptor–positive patients, lower p27 expression was associated with worse overall survival (HR = 1.42, 95% CI = 1.05 to 1.94) and worse disease-free survival (HR = 1.27, 95% CI = 0.99 to 1.63) than higher p27 expression after adjustment for treatment, menopausal status, tumor size, and number of positive lymph nodes. Among these patients, 5-year overall survival associated with higher p27 expression (0.91, 95% CI = 0.89 to 0.93) was similar to that associated with lower p27 expression (0.85, 95% CI = 0.82 to 0.87). No association between p27 expression and survival was found in hormone receptor–negative patients. Cyclin E expression was not statistically significantly associated with overall survival (HR = 1.12, 95% CI = 0.91 to 1.38) or disease-free survival (HR = 1.09, 95% CI = 0.92 to 1.29). Conclusions: Low p27 expression appears to be associated with poor prognosis, especially among patients with steroid receptor–positive tumors.
CiteULike 
Connotea 
Del.icio.us What's this?
Correspondence about this Article
- Re: p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy
- Paul N. Span, Pieter H. de Mulder, and Fred C. G. J. Sweep
J Natl Cancer Inst 2007 99: 738.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
|
|
 |
|
  C. E. Glover, K. E. Gurley, K.-H. Kim, B. Storer, M. L. Fero, and C. J. Kemp Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer Carcinogenesis, June 1, 2009; 30(6): 1058 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Grabowski, J. Schrader, J. Wagner, D. Horsch, R. Arnold, C. N. Arnold, I. Georgieva, H. Stein, M. Zeitz, P. T. Daniel, et al. Loss of Nuclear p27 Expression and Its Prognostic Role in Relation to Cyclin E and p53 Mutation in Gastroenteropancreatic Neuroendocrine Tumors Clin. Cancer Res., November 15, 2008; 14(22): 7378 - 7384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Berglund, M Stighall, K Jirstrom, L Ryden, M Ferno, B Nordenskjold, and G Landberg Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern J. Clin. Pathol., February 1, 2008; 61(2): 184 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Hayes Markers for Predicting and Evaluating Response to Therapy for Breast Cancer ASCO Educational Book, January 1, 2008; 2008(1): 30 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Harris, H. Fritsche, R. Mennel, L. Norton, P. Ravdin, S. Taube, M. R. Somerfield, D. F. Hayes, and R. C. Bast Jr American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5287 - 5312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. N. Span, P. H. de Mulder, and F. C. G. J. Sweep Re: p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy J Natl Cancer Inst, May 2, 2007; 99(9): 738 - 738. [Full Text] [PDF]
|
|