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Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

BRCA mutations contribute to about 20% of all hereditary breast cancers. With full-genome sequencing as the emerging standard for genetic testing, other breast cancer susceptibility genes have been identified and may collectively contribute to up to 30% of all hereditary breast cancers. We re-assessed women who had previously tested negative for a BRCA mutation when outdated techniques were used, and discuss the implications of identifying a mutation several years after initial genetic testing.

Methods

We evaluated the prevalence of mutations in 12 breast cancer susceptibility genes (including BRCA1 and BRCA2) in 190 breast cancer patients with a strong family history of breast cancer. These women had previously tested negative for mutations in the large coding exons of BRCA1 and BRCA2 using the protein truncation test (PTT) between the years of 1996 and 2013.

Results

We identified pathogenic mutations in 17 of 190 (9%) women. Six mutations were detected in BRCA1 (n = 2) and BRCA2 (n = 4). Eleven mutations were found in other breast cancer susceptibility genes including CHEK2 (n = 5), PALB2 (n = 2), BLM (n = 2), ATM (n = 1) and TP53 (n = 1).

Conclusion

Among 190 breast cancer patients with a family history of the disease, and who previously received a negative result for BRCA mutations using the PTT, 17 (9%) women were found to carry a high-risk pathogenic mutation in a breast cancer susceptibility gene. Six of these women were BRCA mutation carriers who were missed previously. These findings support the rationale for updated genetic testing in patients who tested BRCA mutation negative using outdated techniques.

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Acknowledgements

Joanne Kotsopoulos is the recipient of a Cancer Care Ontario Research Chair in Population Studies and a Canadian Cancer Society Career Development Award in Prevention. Steven Narod is the recipient of a Canada Research Chair tier I. Olivia Moran is the recipient of the Enid Walker Graduate Student Award in Women’s Health Research and the Canadian Graduate Scholarship—Master’s award from the Canadian Institutes of Health Research. This study was funded by the Canadian Breast Cancer Foundation—Ontario Chapter Research Project Grant. The authors thank Chantelle Vernon, Nikita Rao, Tracy Graham, Stephanie Hurst, Kathleen Bell, Jeanna McCuaig, Yael Ogniewicz, Sonia Nanda, Spring Holter, Dawn Lee and Nicole Gojska for their help with participant recruitment and interpretation of the findings.

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Authors and Affiliations

  1. Familial Breast Cancer Unit, Women’s College Research Institute, Women’s College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada

    Olivia Moran, Dina Nikitina, Robert Royer, Aletta Poll, Kelly Metcalfe, Steven A. Narod, Mohammad R. Akbari & Joanne Kotsopoulos

  2. Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada

    Olivia Moran, Steven A. Narod & Joanne Kotsopoulos

  3. Lawrence S. Bloomberg Faculty of Nursing, 155 College Street, Toronto, ON, M5T 3M7, Canada

    Kelly Metcalfe

  4. Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada

    Steven A. Narod, Mohammad R. Akbari & Joanne Kotsopoulos

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  1. Olivia Moran
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  2. Dina Nikitina
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  3. Robert Royer
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  4. Aletta Poll
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  6. Steven A. Narod
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  7. Mohammad R. Akbari
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  8. Joanne Kotsopoulos
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Corresponding author

Correspondence to Joanne Kotsopoulos.

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The authors declare that they have no competing interests.

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The experiments described comply with the current laws of the country in which they were performed.

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Moran, O., Nikitina, D., Royer, R. et al. Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel. Breast Cancer Res Treat 161, 135–142 (2017). https://doi.org/10.1007/s10549-016-4038-y

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  • DOI: https://doi.org/10.1007/s10549-016-4038-y

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