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Co-amplification of CCND1 and EMSY is associated with an adverse outcome in ER-positive tamoxifen-treated breast cancers

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Abstract

Amplification of chromosome 11q13 is commonly seen in breast carcinomas and candidate genes from this region include CCND1 and EMSY. Here, we investigate the prognostic significance of CCND1 and EMSY amplification in a large series of breast carcinomas and in BRCA1 and BRCA2 mutation positive breast cancers. Amplification of CCND1 and EMSY was assessed by fluorescent in situ hybridization. Both CCND1 and EMSY amplifications were associated with a significantly worse outcome in ER-positive patients treated with tamoxifen only, in contrast to nonamplified tumors (P = 8.55 × 10−4 and P = 8.35 × 10−5, respectively). In multivariable Cox models, which included standard prognostic markers, co-amplification of CCND1 and EMSY was significantly more predictive of outcome than was amplification of either gene alone or neither gene amplified in ER-positive tamoxifen-treated patients (P = 5.47 × 10−5). EMSY gene amplification was a significantly less common event in BRCA2 mutation carriers as compared to BRCA1 mutation carriers (9 versus 24%, respectively). In contrast, CCND1 amplification occurred at a similar frequency in both BRCA1 and BRCA2 breast cancers (22 versus 18%, respectively). In summary, co-amplification of CCND1 and EMSY identified a poor prognostic subset of ER-positive tamoxifen-treated patients. In addition, EMSY amplification occurred at a lower frequency in BRCA2 mutation carriers providing evidence to support EMSY amplification as a somatic surrogate for BRCA2 loss in sporadic breast cancer.

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Acknowledgments

Research funded by an operating grant from the CBCRI/CIHR awarded to DGH. DGH is a MSFHR senior scholar. The tissue microarray laboratory is supported by a research unit grant from the MSFHR and an unrestricted education grant from Sanofi-avenits Canada. We would like to thank Dr Ake Borg for contributing BRCA1 and BRCA2 mutation positive breast cancers for this study.

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Authors and Affiliations

  1. Center for Translational and Applied Genomics, British Columbia Cancer Agency, 600 W. 10th Ave, Vancouver, BC, V5Z 4E6, Canada

    Lindsay A. Brown, Karynn Johnson & David G. Huntsman

  2. Genetic Pathology Evaluation Center, British Columbia Cancer Agency, Jack Bell Research Center, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada

    Samuel Leung

  3. Departments of Pathology and Oncology, Jewish General Hospital and Program in Cancer Genetics, McGill University, 546 Pine Ave. West, Montreal, QC, H2W 1S6, Canada

    Tarek A. Bismar

  4. Human Cancer Genetics Programme, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, Madrid, 28029, Spain

    Javier Benítez

  5. Program in Cancer Genetics, Gerald Bronfman Centre for Cancer Research, Department of Oncology, McGill University, 546 Pine Ave. West, Montreal, QC, H2W 1S6, Canada

    William D. Foulkes

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  1. Lindsay A. Brown
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  2. Karynn Johnson
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  7. David G. Huntsman
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Correspondence to Lindsay A. Brown.

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Brown, L.A., Johnson, K., Leung, S. et al. Co-amplification of CCND1 and EMSY is associated with an adverse outcome in ER-positive tamoxifen-treated breast cancers. Breast Cancer Res Treat 121, 347–354 (2010). https://doi.org/10.1007/s10549-009-0479-x

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  • DOI: https://doi.org/10.1007/s10549-009-0479-x

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