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Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis

Familial Cancer volume 14, pages 531–538 (2015)Cite this article

Abstract

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2–3 % per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

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Acknowledgments

FL and DGE are supported by the Manchester NIHR Biomedical Research Centre, DGE and AH by the Genesis Breast Cancer Prevention Appeal. AH is supported by Breakthrough Breast Cancer DGE is an NIHR Senior Investigator.

Author contribution

Conception and design: DGE. Collection and assembly of data: DGE, MB, FL. Data analysis and interpretation: NB, JH DGE, SI, AH. Manuscript writing: NB, JH, DGE, SI, AH, FL. Final approval of manuscript: All

Role of funding source

This is unfunded research. The study sponsor had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author confirms that he had full access to all the data in the study and had final responsibility for the decision to submit for publication

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Affiliations

  1. Department of Breast Surgery, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK

    N. N. Basu

  2. Centre for Health Informatics, Institute of Population Health, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester, M13 9PL, UK

    S. Ingham & A. Howell

  3. Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, Manchester, M23 9LT, UK

    N. N. Basu, S. Ingham & D. G. Evans

  4. Wolfson Computer Laboratory, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK

    J. Hodson

  5. Genetic Medicine, St. Mary’s Hospital, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester, M13 9WL, UK

    F. Lalloo, M. Bulman & D. G. Evans

  6. Manchester Breast Centre, Manchester Cancer Research Centre, University of Manchester, Withington, Manchester, M20 4BX, UK

    A. Howell & D. G. Evans

Authors
  1. N. N. Basu
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  2. S. Ingham
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  3. J. Hodson
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  4. F. Lalloo
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  5. M. Bulman
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  6. A. Howell
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  7. D. G. Evans
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Corresponding author

Correspondence to N. N. Basu.

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Basu, N.N., Ingham, S., Hodson, J. et al. Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis. Familial Cancer 14, 531–538 (2015). https://doi.org/10.1007/s10689-015-9825-9

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  • DOI: https://doi.org/10.1007/s10689-015-9825-9

Keywords

  • BRCA1
  • BRCA2
  • Contralateral
  • Breast cancer
  • Risk
  • SNP