TY - JOUR
T1 - Cyclin E and survival in patients with breast cancer
AU - Keyomarsi, Khandan
AU - Tucker, Susan L.
AU - Buchholz, Thomas A.
AU - Callister, Matthew
AU - Ding, Ye
AU - Hortobagyi, Gabriel N.
AU - Bedrosian, Isabelle
AU - Knickerbocker, Christopher
AU - Toyofuku, Wendy
AU - Lowe, Michael
AU - Herliczek, Thaddeus W.
AU - Bacus, Sarah S.
PY - 2002/11/14
Y1 - 2002/11/14
N2 - Background: Cyclin E, a regulator of the cell cycle, affects the behavior of breast-cancer cells. We investigated whether levels of cyclin E in the tumor correlated with survival among patients with breast cancer. Methods: Tumor tissue from 395 patients with breast cancer was assayed for cyclin E, cyclin D1, cyclin D3, and the HER-2/neu oncogene with the use of Western blot analysis. Full-length, low-molecular-weight, and total cyclin E were measured. Immunohistochemical assessments of cyclin E were also made of 256 tumors. We sought correlations between levels of these molecular markers and disease-specific and overall survival. Results: The median follow-up was 6.4 years. A high level of the low-molecular-weight isoforms of cyclin E, as detected by Western blotting, correlated strongly with disease-specific survival whether axillary lymph nodes were negative or positive for metastases (P< 0.001). Among 114 patients with stage I breast cancer, none of the 102 patients with low levels of cyclin E in the tumor had died of breast cancer by five years after diagnosis, whereas all 12 patients with a high level of low-molecular-weight cyclin E had died of breast cancer within that period. In multivariate analysis, a high total cyclin E level or high levels of the low-molecular-weight forms of cyclin E were significantly correlated with poor outcome. The hazard ratio for death from breast cancer for patients with high total cyclin E levels as compared with those with low total cyclin E levels was 13.3 - about eight times as high as the hazard ratios associated with other independent clinical and pathological risk factors. Conclusions: Levels of total cyclin E and low-molecular-weight cyclin E in tumor tissue, as measured by Western blot assay, correlate strongly with survival in patients with breast cancer.
AB - Background: Cyclin E, a regulator of the cell cycle, affects the behavior of breast-cancer cells. We investigated whether levels of cyclin E in the tumor correlated with survival among patients with breast cancer. Methods: Tumor tissue from 395 patients with breast cancer was assayed for cyclin E, cyclin D1, cyclin D3, and the HER-2/neu oncogene with the use of Western blot analysis. Full-length, low-molecular-weight, and total cyclin E were measured. Immunohistochemical assessments of cyclin E were also made of 256 tumors. We sought correlations between levels of these molecular markers and disease-specific and overall survival. Results: The median follow-up was 6.4 years. A high level of the low-molecular-weight isoforms of cyclin E, as detected by Western blotting, correlated strongly with disease-specific survival whether axillary lymph nodes were negative or positive for metastases (P< 0.001). Among 114 patients with stage I breast cancer, none of the 102 patients with low levels of cyclin E in the tumor had died of breast cancer by five years after diagnosis, whereas all 12 patients with a high level of low-molecular-weight cyclin E had died of breast cancer within that period. In multivariate analysis, a high total cyclin E level or high levels of the low-molecular-weight forms of cyclin E were significantly correlated with poor outcome. The hazard ratio for death from breast cancer for patients with high total cyclin E levels as compared with those with low total cyclin E levels was 13.3 - about eight times as high as the hazard ratios associated with other independent clinical and pathological risk factors. Conclusions: Levels of total cyclin E and low-molecular-weight cyclin E in tumor tissue, as measured by Western blot assay, correlate strongly with survival in patients with breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=0037079027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037079027&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa021153
DO - 10.1056/NEJMoa021153
M3 - Article
C2 - 12432043
AN - SCOPUS:0037079027
SN - 0028-4793
VL - 347
SP - 1566
EP - 1575
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 20
ER -