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.
(Less)
- author
- Ahlin, Cecilia
; Lundgren, Claudia
; Embretsén-Varro, Elin
; Jirström, Karin
LU
; Blomqvist, Carl
and Fjällskog, M-L
- organization
- publishing date
- 2017-05-20
- 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
- pmid:28528450
- 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
- 2024-06-09 19:23:53
@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}},
keywords = {{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}},
doi = {{10.1007/s10549-017-4294-5}},
volume = {{164}},
year = {{2017}},
}