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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

Ahlin, Cecilia; Lundgren, Claudia; Embretsén-Varro, Elin; Jirström, Karin LU ; Blomqvist, Carl and Fjällskog, M-L (2017) In Breast Cancer Research and Treatment p.1-12
Abstract

Purpose: 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. Methods: 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... (More)

Purpose: 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. Methods: 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. Results: 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 (ρ 0.19, p = 0.006) and B (ρ 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). Conclusion: 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.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Breast cancer, CCND1, Cyclin D1, Proliferation
in
Breast Cancer Research and Treatment
pages
12 pages
publisher
Springer
external identifiers
  • scopus:85019597976
  • wos:000404777500016
ISSN
0167-6806
DOI
10.1007/s10549-017-4294-5
language
English
LU publication?
yes
id
c3220b9d-b86a-4280-a2d8-7f7e257fc64d
date added to LUP
2017-06-30 14:26:45
date last changed
2017-09-18 11:37:09
@article{c3220b9d-b86a-4280-a2d8-7f7e257fc64d,
  abstract     = {<p>Purpose: 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. Methods: 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. Results: 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 (ρ 0.19, p = 0.006) and B (ρ 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). Conclusion: 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.</p>},
  author       = {Ahlin, Cecilia and Lundgren, Claudia and Embretsén-Varro, Elin and Jirström, Karin and Blomqvist, Carl and Fjällskog, M-L},
  issn         = {0167-6806},
  keyword      = {Breast cancer,CCND1,Cyclin D1,Proliferation},
  language     = {eng},
  month        = {05},
  pages        = {1--12},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  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},
  url          = {http://dx.doi.org/10.1007/s10549-017-4294-5},
  year         = {2017},
}