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      High cyclin B1 expression is associated with poor survival in breast cancer

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          Abstract

          Cyclin B1 regulates the G 2-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.

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          Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

          Marc Buyse, Sherene Loi, Laura Van't Veer … (2006)
          A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.
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            2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology.

            J. Milburn Jessup, N Kemeny, R Bast … (2001)
            To update the 1997 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. Six tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor markers for breast cancer. In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used. A computerized literature search from 1994 to March 1999 was performed. The same values for use, utility, and levels of evidence were used by the committee. The same benefit, harms, and costs were used. Changes were recommended (see Appendix). The updated recommendations were validated by external review by the American Society of Clinical Oncology's (ASCO's) Health Services Research Committee and by ASCO's Board of Directors. American Society of Clinical Oncology.
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              Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication.

              Kwang Hong, Hassan K. Hassan, L. Mao … (2000)
              Cyclin B1 is a key molecule for G2-M-phase transition during the cell cycle and is overexpressed in various tumor types. However, the expression status of cyclin B1 in lung cancer and its clinical significance remain unknown. We used immunohistochemistry studies to examine the expression of cyclin B1 in 77 non-small cell lung cancer specimens from patients with histological stage I disease. All of the patients underwent curative surgical treatment. The median length of follow-up care is 8.2 years. High-level cyclin B1 expression (a cyclin B1 labeling index > or =15%) was observed in 17 of the 77 (22%) tumors. Patients whose tumors expressed a high level of cyclin B1 had a significantly shorter survival time than patients whose tumors expressed a low level of cyclin B1 (P = 0.02, log-rank test). Interestingly, overexpression of cyclin B1 was more frequently observed in tumors with squamous cell histology than in tumors with other histological cell types (P = 0.01, Fisher's exact test). A subgroup analysis revealed that cyclin B1 overexpression seems to be an adverse prognostic factor only in patients with squamous cell carcinoma (SCC) of the lung (P = 0.02, log-rank test). Our data indicate that cyclin B1 may be dysregulated in non-small cell lung cancer, particularly in the SCC subtype, and that a high level of cyclin B1 expression may be a prognostic marker for patients with early-stage SCC of the lung.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Electronic): 17 March 2009
                Publication date Collection: 31 March 2009
                Publication date (Print): 07 April 2009
                Volume: 100
                Issue: 7
                Pages: 1055-1060
                Affiliations
                [1 ]Department of Oncology, Helsinki University Central Hospital, P.O. Box 180 Helsinki FI-00029 HUS, Finland
                [2 ]Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, P.O. Box 140 Helsinki FI-00029 HUS, Finland
                [3 ]Department of Genetics and Pathology, Uppsala University Hospital Uppsala SE-75185, Sweden
                [4 ]Department of Pathology, Helsinki University Central Hospital, P.O. Box 400 Helsinki FI-00029 HUS, Finland
                [5 ]Department of Clinical Genetics, Helsinki University Central Hospital, P.O. Box 140 Helsinki FI-00029 HUS, Finland
                [6 ]Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital Uppsala SE-75185, Sweden
                Author notes
                [* ]Author for correspondence: kirsimari.aaltonen@ 123456helsinki.fi
                Article
                Publisher Item ID: 6604874
                DOI: 10.1038/sj.bjc.6604874
                PMC ID: 2669992
                PubMed ID: 19293801
                SO-VID: f3308b0b-e466-4fe4-aeea-65d7a12925cc
                Copyright © Copyright 2009, Cancer Research UK
                History
                Date revision received : 08 December 2008
                Date accepted : 10 December 2008
                Categories
                Subject: Translational Therapeutics

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cyclin b1,prognosis,breast cancer,survival
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cyclin b1, prognosis, breast cancer, survival

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