High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers

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Ahlin , C , Lundgren , C , Embretsen-Varro , E , Jirstrom , K , Blomqvist , C & Fjallskog , M -L 2017 , ' High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers ' , Breast Cancer Research and Treatment , vol. 164 , no. 3 , pp. 667-678 . https://doi.org/10.1007/s10549-017-4294-5

Title: High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers
Author: Ahlin, Cecilia; Lundgren, Claudia; Embretsen-Varro, Elin; Jirstrom, Karin; Blomqvist, Carl; Fjallskog, M. -L.
Contributor: University of Helsinki, Clinicum
Date: 2017-08
Language: eng
Number of pages: 12
Belongs to series: Breast Cancer Research and Treatment
ISSN: 0167-6806
URI: http://hdl.handle.net/10138/237246
Abstract: Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.
Subject: Breast cancer
Proliferation
Cyclin D1
CCND1
INVASIVE DUCTAL CARCINOMA
ESTROGEN-RECEPTOR STATUS
PROTEIN EXPRESSION
PROGNOSTIC VALUE
POOR-PROGNOSIS
CCND1 AMPLIFICATION
GENE AMPLIFICATION
NEOADJUVANT CHEMOTHERAPY
TAMOXIFEN RESISTANCE
ADJUVANT TAMOXIFEN
3122 Cancers
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