Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.


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Authors
Girardi, Fabio 
Barnes, Daniel R 
Barrowdale, Daniel 
Frost, Debra 
Brady, Angela F 
Abstract

PURPOSE: BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives. METHODS: We used cohort analysis to estimate incidences, cumulative risks, and standardized incidence ratios (SIRs). RESULTS: A total of 1,895 unaffected women were eligible for inclusion in the BC risk analysis and 1,736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% confidence interval (CI) 5.9-15%) by age 85 years and the corresponding risk of EOC was 0.6% (95% CI 0.2-2.6%). The SIR for invasive BC was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in noncarriers from BRCA1 families, and 1.03 (95% CI 0.57-1.87) in noncarriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort. CONCLUSION: Our results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives.

Description
Keywords
BRCA1/BRCA2, breast cancer, ovarian cancer, predictive test negatives, risks, Adult, Aged, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Middle Aged, Ovarian Neoplasms, Risk Assessment, Risk Factors
Journal Title
Genet Med
Conference Name
Journal ISSN
1098-3600
1530-0366
Volume Title
20
Publisher
Elsevier BV
Sponsorship
Cancer Research UK (20861)
Cancer Research Uk (None)
Cancer Research UK (23382)
Cancer Research UK (A11990)
Cancer Research UK (A16563)
Cancer Research UK (A10118)
Cancer Research UK (A17523)