Identification of the best index case significantly improves mutation detection rates in families with hereditary breast and ovarian cancer

To date, a disease-causing mutation can be found in 15-30% of families with hereditary breast and ovarian cancer (HBOC) and it is believed that more than half of the cases still remain unsolved. Usually it is intended to perform genetic analyses in the family member with the most severe phenotype, which, however, may not always be possible. Moreover, no standard criteria have been established to define the person who is most suitable for genetic testing within a family: ‘the best index case’. We therefore established clinical criteria to identify the best index case in HBOC and analyzed the impact on genetic testing. 130 patients who presented at our department from 2016 to 2018 were divided into two groups. In group A (N = 98) genetic analyses were performed in the best index case based on our criteria. In group B (N = 32) at least one other family member was considered a better index case. The detection rate of expected mutations was significantly higher for group A (64.3% vs. 32.0%, p = 0.034) while there was no significant difference of calculated mutation carrier risks between these groups. We conclude that the mutation detection rate in families with HBOC is notably higher after identifying the best index case for genetic testing according to the clinical selection criteria reported here.