Factors predictingBRCA1/2pathogenic variants in patients with ovarian cancer: a systematic review with meta-analysis

Abstract

AimTo provide accurate figures of the frequency of specific clinical features in ovarian cancer (OC) associated with germlineBRCA1/2pathogenic variants and to define their relevance in predicting the presence of a germline pathogenic variant in these genes.MethodsA systematic review of papers published from 1995 to February 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data from eligible papers were synthesised through meta-analysis.ResultsThirty-seven papers were reviewed, including a total of 12 886 patients with OC. AmongBRCAcarriers, 86.4% displayed serous type, 83.3% high grade (G3), 83.7% FIGO (The International Federation of Gynecology and Obstetrics) stage III/IV, 39.7% age at diagnosis ≤50 years and 18.1% personal breast cancer history, while the frequency of these features in non-carriers resulted significantly lower (p<0.001). The meta-analysis showed that the strongest predictor ofBRCA1/2pathogenic variants was a personal breast cancer history (OR 5.21, 95% CI 4.02 to 6.55, compared with no previous breast cancer), followed by high grade (OR 2.47, 95% CI 1.97 to 3.10, compared with low/intermediate grade), serous histotype (OR 2.33, 95% CI 2.07 to 2.64, compared with other histotypes), advanced (III/IV) FIGO stage (OR 1.89, 95% CI 1.67 to 2.15, compared with stage I/II) and age at diagnosis ≤50 years (OR 1.20, 95% CI 1.01 to 1.42, compared with >50 years).ConclusionThe results of this meta-analysis provide data on features increasing the prior probability of findingBRCA1/2pathogenic variants that may prove helpful in counselling patients and prioritising testing.PROSPERO registration numberCRD42021271815.