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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

Lundgren, Katja LU ; Brown, Matthew; Pineda, Silvia; Cuzick, Jack; Salter, Janine; Zabaglo, Lila; Howell, Anthony; Dowsett, Mitch and Landberg, Goeran (2012) In Breast Cancer Research 14(2).
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
14
issue
2
publisher
BioMed Central
external identifiers
  • wos:000304771800032
  • scopus:84859189826
ISSN
1465-5411
DOI
10.1186/bcr3161
language
English
LU publication?
yes
id
6242dda7-b4fa-4174-8211-56b75eaa3cb1 (old id 2906376)
date added to LUP
2012-08-01 09:45:46
date last changed
2017-09-24 03:04:25
@article{6242dda7-b4fa-4174-8211-56b75eaa3cb1,
  abstract     = {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.},
  author       = {Lundgren, Katja and Brown, Matthew and Pineda, Silvia and Cuzick, Jack and Salter, Janine and Zabaglo, Lila and Howell, Anthony and Dowsett, Mitch and Landberg, Goeran},
  issn         = {1465-5411},
  language     = {eng},
  number       = {2},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {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},
  url          = {http://dx.doi.org/10.1186/bcr3161},
  volume       = {14},
  year         = {2012},
}