Fig. 1. Scoring of at-risk and tested family members.

In this fictitious pedigree (A), a pathogenic BRCA1 germline variant was identified in the proband affected with breast cancer (III-1). Subsequently, both her parents were tested and, as expected based on pedigree data (no breast or ovarian cancer had occurred in the maternal family members, data not shown), the father of the proband proved to be a carrier of the pathogenic germline BRCA1 variant. As a next step, a letter was sent to the family for circulation amongst the proband’s at-risk paternal family members. Testing of the proband and both her parents was labelled as diagnostic testing, while subsequent testing of additional family members was labelled as predictive or confirmatory testing for unaffected and affected at-risk relatives, respectively. When the family first received the letter, five adult relatives were at 50% risk, or at 25% risk if a parent at 50% risk was deceased, comprising the relatives II-4, II-5, III-2, III-3 and III-4. Three of these five relatives were tested. It should be noted that additional family members were tested, including III-5 and III-6 once they learned that their mother did not wish to be tested, and III-8 based on cascade testing after her father was found to be mutation carrier. In the current study, II-4 was scored as untested; however, the fact that the offspring III-5 and III-6 were tested is relevant and is given as extra information in Table 1. The fact that individual III-8 was tested has been added to the total number of tested family members, but individual III-8 was not counted as an at-risk family member since she was originally not at-risk (before her father was tested) according to the criteria used.