RT Journal Article
T1 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
A1 Lundgren, Katja
A1 Brown, Matthew
A1 Pineda Sanjuan, Silvia
A1 Cuzick, Jack
A1 Salter, Janine
A1 Zabaglo, Lila
A1 Howell, Anthony
A1 Dowsett, Mitch
A1 Landberg, Göran
A1 TransATAC investigators, 
AB 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.
PB BioMed Central (BMC) - Springer Nature
SN 1465-542X
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/97380
UL https://hdl.handle.net/20.500.14352/97380
LA eng
NO Lundgren, K., Brown, M., Pineda, S. et al. 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. Breast Cancer Res 14, R57 (2012). https://doi.org/10.1186/bcr3161
NO Lund University
NO Malmö University Hospital
NO Swedish Breast Cancer group
NO AstraZeneca
NO Roche
NO Cancer Fundation (Suecia)
NO Knut och Alice Wallenbergs Stiftelse (Suecia)
NO Swedish Reasearch Council
NO Breakthrough Breast Cancer Unit (Reino Unido)
DS Docta Complutense
RD 18 abr 2025