Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 507
© 2005 American Society of Clinical Oncology

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Abstract

Prognostic value of cell cycle regulators p27 and cyclin E: Tissue microarray analysis of 1753 women enrolled in SWOG breast cancer trial 9313

Fred Hutchinson Cancer Research Ctr, Seattle, WA; Univ of Texas Health Sciences Ctr, San Antonio, TX; Mayo Clinic, Rochester, MN; Ohio State Univ, Columbus, OH; Indiana Univ, Indianapolis, IN; Univ of Washington, Seattle, WA; Univ of Michigan, Ann Arbor, MI

507

Background: Abnormal cell proliferation is a common feature of neoplasia and associations between poor clinical outcome and abnormal expression of cell cycle regulatory proteins have been shown in population-based and clinical studies. Methods: Using tissue microarray, we evaluated the prognostic value of cell cycle regulators p27 and cyclin E by IHC in 1,753 of 3,122 (56%) women enrolled in SWOG Intergroup Trial 9313. The protocol compared DFS and OS in women with primary breast cancer who received doxorubicin and cyclophosphamide administered either concurrently (n=1595) or sequentially (n=1527). The two arms of the study showed equivalence of treatment regimens, p=0.26 (Haskell CM; Proc ASCO 21:36a (#142), 2002). Median age was 47 (range 21–76); data collected included race, stage, and menopausal nodal, and ER/PR status. Expression of p27 and cyclin E was rated from 1–7 and dichotomized at the median score for Cox regression analysis. Median follow-up is 7 years. Results: p27 was below median expression (1–5) in 51% and cyclin E above median (4–7) in 47% of tumors. Adjusted for tumor size, number of positive nodes, surgery type, menopause status, and black race, both low p27 and high cyclin E were significant predictors of poorer OS (p=.0001 and.036 respectively) and poorer DFS (p=.0011 and.048 respectively). After adjustment for ER and PR, p27 continued to predict OS (p=.011) and DFS (p=.047); Cyclin E no longer predicted OS (p=.37) or DFS (p=.37). For ER negative tumors, neither cyclin E nor p27 predicted OS or DFS. For ER positive tumors, Cyclin E was not predictive, but p27 predicted OS (p=.002) and DFS (p=.005).The hazard ratio for OS in ER positive women was 0.56 (95% CI 0.39–0.80) in favor of high p27. Conclusions: The study demonstrates the value of TMA in a clinical trial and is the first evaluation of survival by p27 and cyclin E expression in similarly treated women. Low or absent p27 expression in women treated with AC predicted poor OS and DFS. In the subgroup of women with ER positive tumors, it also predicted decreased OS and DFS. Additional large studies are needed to fully understand the relationship between abnormal expression of cell cycle regulators and treatment response.

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting