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Does the age of breast cancer diagnosis in first-degree relatives impact on the risk of breast cancer in BRCA1 and BRCA2 mutation carriers?

  • Epidemiology
  • Published:
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Abstract

The purpose of this study is to estimate the age-specific annual risks of breast cancer in a woman with a germline BRCA mutation and an affected first-degree relative according to the age of breast cancer diagnosis in the relative. Women with BRCA mutations with no previous diagnosis of breast cancer and with one first-degree relative with breast cancer were followed for breast cancers for a mean of 5.9 years (minimum 2 years). Age-specific annual breast cancer risks were calculated, according to the age of breast cancer diagnosis in the proband and the first-degree relative. 1114 cancer-free women with a BRCA mutation with a single first-degree relative with breast cancer were eligible for the study. 122 women (11.0 %) were diagnosed with incident breast cancer. The annual risk of breast cancer was 2.0 % for women with BRCA1 mutations and was 1.6 % for women with BRCA2 mutations. The age of breast cancer diagnosis in the first-degree relative did not affect the annual breast cancer risks for BRCA1 mutation carriers. For BRCA2 mutation carriers, the annual breast cancer risk was 4.5 % for women with a first-degree relative diagnosed with breast cancer under the age of 30 years and was 0.7 % for women with a relative diagnosed over the age of 60. Among women with BRCA2 mutations, a family history of early-onset breast cancer is a risk factor for developing breast cancer. Risk assessment for healthy BRCA2 mutation carriers should consider the ages of breast cancers diagnosed in first-degree relatives.

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Acknowledgments

Dr. John Semple is supported through the Canadian Breast Cancer Foundation (Ontario Chapter). This work is supported through the Canadian Cancer Society Research Initiative. C.E. is the Sondra J. and Stephen R. Hardis Endowed Chair in Cancer Genomic Medicine at the Cleveland Clinic and an ACS Clinical Research Professor. This study complies with the current laws of the country in which it was performed. This study was carried out in Canada.

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Authors and Affiliations

  1. Women’s College Research Institute, 790 Bay Street, Toronto, ON, Canada

    John Semple, Kelly A. Metcalfe, Javaid Iqbal & Steven A. Narod

  2. Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada

    Kelly A. Metcalfe

  3. Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

    Jan Lubinski, Tomasz Huzarski & Jacek Gronwald

  4. University Health Network, Toronto, ON, Canada

    Susan Armel

  5. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA

    Henry T. Lynch

  6. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Beverly Hills, CA, USA

    Beth Karlan

  7. Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada

    William Foulkes

  8. Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Christian F. Singer

  9. Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA

    Susan L. Neuhausen

  10. Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Taussig Cancer Institute, Cleveland, OH, USA

    Charis Eng

  11. Stanley Shalom Zielony Institute of Nursing Excellence, Cleveland Clinic, Cleveland, USA

    Charis Eng

  12. Department of Genetics and Genome Sciences, and Germline High Risk Cancer Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Charis Eng

Authors
  1. John Semple
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  2. Kelly A. Metcalfe
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  3. Jan Lubinski
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  4. Tomasz Huzarski
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  5. Jacek Gronwald
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  6. Susan Armel
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  7. Henry T. Lynch
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  8. Beth Karlan
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  9. William Foulkes
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  10. Christian F. Singer
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  11. Susan L. Neuhausen
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  12. Charis Eng
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  13. Javaid Iqbal
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  14. Steven A. Narod
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the Hereditary Breast Cancer Clinical Study Group

Corresponding author

Correspondence to Steven A. Narod.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

The members of the Hereditary Breast Cancer Clinical Study Group were available in the Appendix.

Appendix: Hereditary breast cancer clinical study group:

Appendix: Hereditary breast cancer clinical study group:

P. Ainsworth, L. Bordeleau, T. Byrski, A. Chudley, F. Couch, C. Cullinane, C. Cybulski, M. Daly, R. Demsky, T. Donenberg, A. Eisen, G. Evans, T. Fallen, E. Friedman, J. Garber, D. Gilchrist, O. Ginsburg, B. Gorski, C. Isaacs, N. Kauff, J. Klijn, E. Lemire, L. Maehle, S. Manoukian, J. McCuaig, W. McKinnon, J. McLennan, W. Meschino, P. Moller, K. Offit, O. Olopade, B. Pasini, D. Rayson, B. Rosen, H. Saal, L. Senter, C. Singer, D. Stoppa–Lyonnet, K. Sweet, E. Warner, J. Weitzel, M. Wood, and D. Zakalik.

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Semple, J., Metcalfe, K.A., Lubinski, J. et al. Does the age of breast cancer diagnosis in first-degree relatives impact on the risk of breast cancer in BRCA1 and BRCA2 mutation carriers?. Breast Cancer Res Treat 154, 163–169 (2015). https://doi.org/10.1007/s10549-015-3596-8

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  • DOI: https://doi.org/10.1007/s10549-015-3596-8

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