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

被引:78
作者
Lundgren, Katja [1 ,2 ]
Brown, Matthew [1 ]
Pineda, Silvia [3 ]
Cuzick, Jack [3 ]
Salter, Janine [4 ]
Zabaglo, Lila [4 ]
Howell, Anthony [1 ]
Dowsett, Mitch [4 ,5 ]
Landberg, Goeran [1 ,6 ]
机构
[1] Univ Manchester, Breakthrough Breast Canc Res Unit, Sch Canc Enabling Sci & Technol,Christie NHS Fdn, Manchester Acad Hlth Sci Ctr,Paterson Inst Canc R, Manchester M20 4BX, Lancs, England
[2] Lund Univ, Ctr Mol Pathol, Dept Lab Med, Malmo Univ Hosp, SE-20502 Malmo, Sweden
[3] Queen Mary Univ London, Canc Res UK Ctr Epidemiol Math & Stat, Wolfson Inst Prevent Med, London EC1M 6BQ, England
[4] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England
[5] Royal Marsden Hosp, London SW3 6JJ, England
[6] Univ Gothenburg, Sahlgrenska Canc Ctr, S-40530 Gothenburg, Sweden
基金
瑞典研究理事会;
关键词
ESTROGEN-RECEPTOR STATUS; ADJUVANT TREATMENT; PROGNOSTIC VALUE; ENDOCRINE THERAPY; D1; OVEREXPRESSION; GROWTH; COMBINATION; CARCINOMAS; ARIMIDEX;
D O I
10.1186/bcr3161
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:11
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