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Open Access 01-04-2012 | Research article

Effects of cyclin D₁ gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study

Authors: Katja Lundgren, Matthew Brown, Silvia Pineda, Jack Cuzick, Janine Salter, Lila Zabaglo, Anthony Howell, Mitch Dowsett, Göran Landberg, the TransATAC investigators

Published in: Breast Cancer Research | Issue 2/2012

Abstract

Introduction

Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D₁ 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 D₁ 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 D₁ 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 D₁ 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 D₁ 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 D₁ predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.

Trial Registration

Current Controlled Trials ISRCTN18233230.

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Title: Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study
Authors: Katja Lundgren
Matthew Brown
Silvia Pineda
Jack Cuzick
Janine Salter
Lila Zabaglo
Anthony Howell
Mitch Dowsett
Göran Landberg
the TransATAC investigators
Publication date: 01-04-2012
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr3161

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Abstract

Introduction

Methods

Results

Conclusions

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