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

Girardi, Fabio, Barnes, Daniel R., Barrowdale, Daniel, Frost, Debra, Brady, Angela F., Miller, Claire, Henderson, Alex, Donaldson, Alan, Murray, Alex, Brewer, Carole, Pottinger, Caroline, Evans, D. Gareth, Eccles, Diana, Lalloo, Fiona, Gregory, Helen, Cook, Jackie, Eason, Jacqueline, Adlard, Julian, Barwell, Julian, Ong, Kai Ren, Walker, Lisa, Izatt, Louise, Side, Lucy E., Kennedy, M John, Tischkowitz, Marc, Rogers, Mark T., Porteous, Mary E., Morrison, Patrick J., Eeles, Ros, Davidson, Rosemarie, Snape, Katie, Easton, Douglas F. and Antoniou, Antonis C. 2018. Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study. Genetics in Medicine 10.1038/gim.2018.44

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1098-3600
Date of First Compliant Deposit: 27 April 2018
Date of Acceptance: 12 January 2018
Last Modified: 30 Apr 2018 10:00
URI: http://orca.cf.ac.uk/id/eprint/111052

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