Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer

Peters, María Giselle; Vidal, M; Giménez, Liliana; Mauro, Laura J.; Armanasco, Eduardo; Cresta, Carlos; Joffé, Elisa Bal de Kier; Puricelli, Lydia

doi:10.3892/or.12.5.1143

Cited by 14 publications

(19 citation statements)

References 30 publications

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“…Our study is the largest so far showing the association of high cyclin B1 and shorter survival in breast cancer. One earlier smaller study with stage I -II tumours did not show any association (Peters et al, 2004), one with 109 tumours showed association with only nuclear staining (Suzuki et al, 2007) and one with 73 tumours showed a significant association (Winters et al, 2001). In the hitherto largest study of 332 tumours, all N-negative, cyclin B1 was associated with poor prognosis but not in multivariate analysis including Ki67 , and when 273 tumours with only surgery and postoperative radiation were analysed, cyclin B1 was prognostic only in premenopausal patients .…”

Section: Discussionmentioning

confidence: 99%

“…Among the 273 tumours treated with surgery and postoperative radiation only, cyclin B1 was an independent predictor of poor overall survival among premenopausal but not postmenopausal or all patients . A further study with 56 invasive stage I -II cancers did not show any association between cyclin B1 expression and prognosis (Peters et al, 2004). A recent study with 109 breast cancers suggested that nuclear cyclin B1 expression was an independent prognostic factor (Suzuki et al, 2007).…”

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confidence: 99%

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

et al. 2009

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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, Po0.0005 and RR 3.51, Po0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P ¼ 0.04 and RR 2.31, P ¼ 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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Section: Discussionmentioning

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

et al. 2009

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“…According to the inclusion and exclusion criteria, there were 14 eligible studies published from 1996 to 2004 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). There were 2 studies, reported by Rudolph et al (19) and Kühling et al (24), based on the same patient cohort.…”

Section: Description Of Studiesmentioning

confidence: 95%

Cyclin E Expression and Prognosis in Breast Cancer Patients: A Meta-Analysis of Published Studies

Wang

Shao

2006

Cancer Investigation

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In vitro studies showed that cyclin E can accelerate the cell cycle by shorten the G1/S phase transition. Therefore, varieties of studies have investigated the relationship between cyclin E and survival in breast cancer patients. However, the results differed widely between studies. We reviewed the published studies and performed a meta-analysis, which including 12 independent studies and 2,534 patients. The combined HR estimate for relapse-free survival (RFS) was 2.32 (95% CI, 1.25-4.30) and 1.72 (95% CI, 0.95-3.10) in univariate and multivariate analysis, respectively. In addition, the combined HR estimate for overall survival (OS) and breast cancer specific survival (BCSS) was 2.98 (95% CI, 1.85-4.78) and 2.86 (95% CI, 1.85-4.41) in univariate and multivariate analysis, respectively. In conclusion, the high level of cyclin E appears to be an independent prognostic factor to OS/BCSS of breast cancer patients but not to RFS.

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“…p27 has been implicated as a tumor suppressor gene in a variety of human cancers and reduction or complete loss of p27 protein has been described in human tumors and shown to correlate with poor patient prognosis (Peters et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis

et al. 2005

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Here, we describe the surprising residual capability of the Rb pathway to negatively regulate proliferation and tumorigenesis in a SV40 large T antigen (Tag)-driven mouse model of pancreatic islet carcinogenesis. Heterogeneous Tag expression during all progression stages suggested that a threshold level of the T antigen oncoprotein might be deterministic for b-cell hyperproliferation and led us to hypothesize that Tag might not be fully inhibiting the tumor suppressor activity of Rb. Moreover, genomic profiling of these tumors by array CGH pointed to regions of loss on chromosomes 6 and 14, where the Rb pathway inhibitor p27 and Rb itself, respectively, reside. Indeed, genetic ablation of the p27 Kip1 or Rb genes accentuated Tag-induced tumorigenesis, with loss of Rb in particular broadly enhancing multiple parameters of tumorigenesis including the frequency and growth rates of premalignant lesions, of nascent solid tumors, and of invasive carcinomas. The data indicate that attenuation rather than complete inactivation of Rb tumor suppressor gene function, in the context of p53 inhibition, is sufficient to initiate tumorigenesis in this model of islet cell cancer, with the demonstrable possibility that subsequent losses of Rb or its regulators can enhance malignant progression. The results may be relevant to human papillomavirus (HPV)-induced cervical neoplasias where E7 oncogene expression levels or activity (in the case of intermediate/low-risk HPV subtypes) incompletely inhibits Rb tumor suppressor functions, as well as to other neoplasias where initiating oncogenic or tumor suppressor events reduce but do not abrogate Rb function.

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Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer

Cited by 14 publications

References 30 publications

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

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

Cyclin E Expression and Prognosis in Breast Cancer Patients: A Meta-Analysis of Published Studies

Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis

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