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

Abstract

Purpose

BRCA1/BRCA2 predictive test negatives are proven non-carriers 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 standardised incidence ratios (SIR).

Results

A total of 1895 unaffected women were eligible for inclusion in the BC risk analysis and 1736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% 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 non-carriers from BRCA1 families and 1.03 (95% CI 0.57-1.87) in non-carriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort.

Conclusions

Our results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives.

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