Differential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer.
Searching for new prognostic factors, we investigated the influence of cyclin expression on breast cancer prognosis. A total of 273 archival tumor specimens from patients with pT1/pT2 N0 breast cancers treated by surgery and local irradiation were immunostained for cyclins E, A and B. Outcome was evaluated as metastasis-free (MFS) and disease-specific survival (DSS) over a median observation period of 99 months. In postmenopausal women, DSS was significantly predicted by cyclin E, and in premenopausal patients by cyclin B. No statistical significance was found for cyclin A. When the prognostic impact of cyclins was compared to that of standard prognostic indicators in a multivariate analysis, both cyclin E and cyclin B were selected as independent predictors of survival in postmenopausal and premenopausal patients, respectively. After inclusion of Ki-67 in the model, cyclin E lost its significance, whereas cyclin B remained the only independent prognostic factor with a hazard ratio of 4.5 (p = 0.026) for tumor-related death. Assessment of cyclin expression may, therefore, refine current prognostic models if considered in relation to menopausal status. The prognostic relevance of cyclins is likely attributable to an influence on proliferation, cell survival and genetic instability. Awareness of the molecular mechanisms leading to deregulated cyclin expression may guide decisions for risk-adapted therapy regimens.
Department of Pathology, University of Kiel, Michaelisstrasse 11, 24105 Kiel, Germany. prudolph@path.uni-kiel.de
Pierre
P
Rudolph
Heidi
H
Kühling
Per
P
Alm
Mårten
M
Fernö
Bo
B
Baldetorp
Håkan
H
Olsson
Reza
R
Parwaresch
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D002453:Cell Cycle; D015331:Cohort Studies; D003131:Combined Modality Therapy; D019926:Cyclin B / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D015993:Life Tables; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D008940:Mitotic Index; D009363:Neoplasm Proteins / Q000032:analysis*; D017698:Postmenopause; D017697:Premenopause; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D011987:Receptors, Steroid / Q000032:analysis; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
D019926:Cyclin B; D019927:Cyclin E; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D011987:Receptors, Steroid