How to identify the best index case in families with hereditary breast and ovarian cancer

Abstract

To date, a disease-causing mutation can be found in approximately 15-30% of families with hereditary breast and ovarian cancer and still more than half of the cases remain unsolved. Usually it is intended to perform genetic analyses in the family member with the most severe phenotype, which, however, is not always 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. This study now establishes clinical selection criteria to identify the best index case in families with hereditary breast and ovarian cancer and analyses the impact on genetic testing. 130 patients who presented at our department from 2016 to 2018 were divided into two groups. In group A, genetic analyses were performed in the best index case (N = 98). In group B, at least one family member had a more severe phenotype compared to the person who was tested (N = 32). The mutation detection rate was significantly higher for group A compared to group B (64.3% vs. 32.0%, p = 0.034), even though there was no significant difference of calculated mutation carrier risks between these groups. Furthermore, the mutation detection rate in group A was notably higher compared to the results of previous studies. We conclude that the mutation detection rate in families with hereditary breast and ovarian cancer can be improved by identifying the best index case for genetic testing according to the clinical selection criteria reported here and suggest that these can be used as a guideline for genetic counseling.