UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

Abstract

Germline pathogenic variants (GPVs) in the cancer predisposition genesBRCA1,BRCA2,MLH1,MSH2,MSH6,BRIP1,PALB2,RAD51DandRAD51Care identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV inBRCA1,BRCA2,MLH1,MSH2andMSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV inBRIP1,PALB2,RAD51DandRAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition ofRAD51Cand RAD51Das OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management ofBRIP1,PALB2,RAD51DandRAD51Ccarriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.