The uptake of predictive DNA-testing in 40 BRCA1/ BRCA2 mutation-positive families. An evaluation of the standard proband-mediated procedure

Fred H Menko, Kiki N. Jeanson, Eveline M.A. Bleiker, Carla W.M. van Tiggelen, Frans B.L. Hogervorst, Jacqueline A. ter Stege, Daoud Ait Moha, Lizet E. van der Kolk

Antoni van Leeuwenhoek Hospital, the Netherlands Cancer Institute, Amsterdam, Netherlands



After the genetic diagnosis of hereditary breast ovarian cancer the proband is requested to inform her or his at-risk family members. In the Netherlands, in 2012, a new guideline was introduced aimed at improving this proband-mediated procedure.


To evaluate the uptake of BRCA1/ BRCA2testing in 40 consecutive families diagnosed in our centre in 2014.


We performed a retrospective observational study of all 40 families in which in 2014 a pathogenic BRCA1/ BRCA2mutation was identified. We reviewed pedigree information and scored the uptake of predictive testing from 2014-2018.


Two families were excluded. In the remaining 38 families a mean of 3.7 predictive tests (range 0-14) was performed. Among 249 adult family members at 50% or 25% risk of being mutation carrier 101 (41%) were tested. Among 107 females 25-75 years of age and at 50% risk 56 (52%) underwent predictive testing, among 40 males with daughters ≥ 18 years and at 50% risk 21 (53%) were tested. Multiple factors were identified that complicated cascade screening, including family members living abroad, probands not wanting to share information and limited pedigree information.


The standard proband-mediated procedure of informing relatives is far from optimal. We suggest that the standard proband-mediated procedure is replaced by a tailored approach for each family including the option of direct contact with at-risk family members by the geneticist. In addition, we suggest detailed monitoring and follow-up of families to evaluate these alternative procedures.