title: Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel.
abstract: 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 We re-assessed women who had previously tested negative for a BRCA mutation when outdated techniques were used, and discuss the implications of identifying a mutation several years after initial genetic testing.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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 These findings support the rationale for updated genetic testing in patients who tested BRCA mutation negative using outdated techniques.
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.|Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada.
authors: Olivia
authors: O
authors: Moran
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
authors: Dina
authors: D
authors: Nikitina
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
authors: Robert
authors: R
authors: Royer
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
authors: Aletta
authors: A
authors: Poll
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.|Lawrence S. Bloomberg Faculty of Nursing, 155 College Street, Toronto, ON, M5T 3M7, Canada.
authors: Kelly
authors: K
authors: Metcalfe
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.|Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada.|Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada.
authors: Steven A
authors: SA
authors: Narod
authors: Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.|Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada.
authors: Mohammad R
authors: MR
authors: Akbari
authors: 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.|Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada. joanne.kotsopoulos@wchospital.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada. joanne.kotsopoulos@wchospital.ca.
authors: Joanne
authors: J
authors: Kotsopoulos
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor
keywords: BRCA1; BRCA2; Breast cancer; Family history; Genetic testing; Susceptibility genes