期刊
JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 98, 期 23, 页码 1723-1731出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djj467
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- NCI NIH HHS [CA58686, U10 CA058861, U10 CA063844, U10 CA042777, CA25224, CA31946, CA58658, U10 CA058416, U10 CA031946, CA74647, CA35192, U10 CA045377, U10 CA013612, U10 CA035431, U10 CA045450, CA63845, U10 CA035119, CA42777, CA52654, U10 CA032102, U10 CA049883, U10 CA046441, N01 CA004919, U10 CA046113, CA22433, N01 CA035431, CA35117, N01 CA035119, N01 CA046441, U10 CA032291, U10 CA035090, U10 CA025224, CA37981, U10 CA022433, CA58416, U10 CA058686, U10 CA027057, CA76462, U10 CA012644, CA04920, U10 CA046368, U10 CA016385, N01 CA067575, CA45450, U10 CA052654, CA49883, U10 CA035261, CA21115, CA46282, CA76429, N01 CA027057, U10 CA067575, CA35261, CA14028, N01 CA038926, CA45377, U10 CA074647, CA35090, CA76132, N01 CA063844, U10 CA046282, U10 CA004919, U10 CA037981, CA46368, CA46113, CA20319, CA68183, N01 CA013612, U10 CA063845, CA58415, CA76447, CA16385, U10 CA035192, CA32291, U10 CA021115, U10 CA038926-24, CA12644, U10 CA076447, N01 CA032102, U10 CA045560, U10 CA014028, U10 CA020319, U10 CA038926, N01 CA045560, U10 CA068183] Funding Source: Medline
Background: Abnormal expression of the cell cycle regulatory proteins p27(Kip1) (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 114111 = 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.
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