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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 164(3). p.667-678
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
published
subject
keywords
Breast cancer, CCND1, Cyclin D1, Proliferation
in
Breast Cancer Research and Treatment
volume
164
issue
3
pages
667 - 678
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
2018-10-31 18:47:55
@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},
  number       = {3},
  pages        = {667--678},
  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},
  volume       = {164},
  year         = {2017},
}