Germline BRCA1/2 mutations are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC). Whenever possible, Index testing should be done in a family member with a previous breast or ovarian cancer (affected individuals, AI) and not in non-affected individuals (NAI). In here we review the characteristics, decisional process and BRCA1/2 mutation detection rate of index testing in AI and NAI.
Analysis of all consecutive HBOC files registered from November 2000-December 2017. The BRCAPRO model was applied to affected patients (pts) and the Tyrer-Cuzick model to all non-affected female individuals. Comprehensive BRCA1/2 analysis was done, including MLPA and c.156_157insAlu testing (Machado PM et al., 2007)
6112 individuals were counseled and 4642 (76%) consented on genetic BRCA1/2 testing: 3420 (56%) index pts and 1222 (20%) family relatives. Index pts: 3361 (98.3%) had a previous cancer diagnosis (AI) and 59 were NAI. Both groups included mostly women (AI-95.2%; NAI-97%). The mean age for NAI was 40.7 years (20-79) and 79% had at least one-first degree relative with breast or ovarian cancer. Testing decision for NAI: either affected relatives were dead (80%), refused testing (15%) or were unreachable (5%). The global BRCA1/2 detection rate for index pts was 10.44%, being higher (13.6%) for NAI index cases (8 pathogenic variants: 2 BRCA1, 6 BRCA2). The mean pretest BRCA mutation probability (P) for NAI was 10.72% (range 0.06-42.8). This P was 18,5% for those who tested positive and 9,45% for inconclusive results ( p > 0.05). The pre-test lifetime breast cancer risk was 26.69% for all NA cases, being higher for those found to be BRCA1/2 carriers (36.07% vs 28.04%).
Our conservative approach allowed for a detection rate in NAI that compared favorably to affected index pts. Although some groups propose widespread BRCA1/2 screening we suggest that NAI should be tested as index only if no cancer relatives are available. Despite the small sample size, the BRCA pre-test probability of 10% or higher seems to increase the detection rate in this subgroup.
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All authors have declared no conflicts of interest.