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Breast Cancer Res Treat. 2017 Jan;161(1):135-142. doi: 10.1007/s10549-016-4038-y. Epub 2016 Oct 31.

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

Author information

1
Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
2
Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada.
3
Lawrence S. Bloomberg Faculty of Nursing, 155 College Street, Toronto, ON, M5T 3M7, Canada.
4
Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada.
5
Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada. joanne.kotsopoulos@wchospital.ca.
6
Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada. joanne.kotsopoulos@wchospital.ca.
7
Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada. joanne.kotsopoulos@wchospital.ca.

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 We re-assessed women who had previously tested negative for a BRCA mutation when outdated techniques were used, and discuss the implications of identifying a mutation several years after initial genetic testing.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.

KEYWORDS:

BRCA1; BRCA2; Breast cancer; Family history; Genetic testing; Susceptibility genes

PMID:
27798748
DOI:
10.1007/s10549-016-4038-y
[Indexed for MEDLINE]

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