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Effects of cyclin D...
Effects of cyclin D-1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study
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- Lundgren, Katja (author)
- Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
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Brown, M. (author)
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Pineda, S. (author)
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Cuzick, J. (author)
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Salter, J. (author)
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Zabaglo, L. (author)
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Howell, A. (author)
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Dowsett, M. (author)
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- Landberg, Göran, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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(creator_code:org_t)
- 2012-04-04
- 2012
- English.
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 14:2
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Abstract
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- Introduction: Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D-1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen. Methods: To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D-1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The CCND1 amplification status and protein expression of cyclin D-1 were assessed by chromogenic in situ hybridisation and immunohistochemistry, respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer patients included in the TransATAC substudy. Results: Amplification of CCND1 was observed in 8.7% of the tumours and was associated with increased risk of disease recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after adjustment for other clinicopathological parameters. In contrast, nuclear expression of cyclin D-1 protein was associated with decreased recurrence rate (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of nuclear or cytoplasmic expression was not of prognostic value. There was no significant interaction between cyclin D-1 status and treatment efficacy, ruling out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal breast cancer. Conclusions: In summary, CCND1 amplification and low nuclear expression of cyclin D-1 predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- estrogen-receptor status
- prognostic value
- adjuvant tamoxifen
- combination trial
- endocrine therapy
- d1
- overexpression
- growth
- carcinomas
- resistance
- intosh gg
- 1995
- oncogene
- v11
- p885
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lundgren, Katja
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Brown, M.
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Pineda, S.
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Cuzick, J.
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Salter, J.
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Zabaglo, L.
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show more...
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Howell, A.
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Dowsett, M.
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Landberg, Göran, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Breast Cancer Re ...
- By the university
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University of Gothenburg
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Lund University