Pathogenic variant detection rate varies considerably in male breast cancer families and sporadic cases: minimal additional contribution beyondBRCA2, BRCA1andCHEK2

BackgroundMale breast cancer (MBC) affects around 1 in 1000 men and is known to have a higher underlying component of high and moderate risk gene pathogenic variants (PVs) than female breast cancer, particularly inBRCA2. However, most studies only report overall detection rates without assessing detailed family history.MethodsWe reviewed germline testing in 204 families including at least one MBC forBRCA1,BRCA2,CHEK2c.1100DelC and an extended panel in 93 of these families. Individuals had MBC (n=118), female breast cancer (FBC)(n=80), ovarian cancer (n=3) or prostate cancer-(n=3). Prior probability of having aBRCA1/2PV was assessed using the Manchester Scoring System (MSS).ResultsIn the 204 families,BRCA2was the major contributor, with 51 (25%) having PVs, followed byBRCA1andCHEK2,with five each (2.45%) but no additional PVs identified, including in families with high genetic likelihood on MSS. Detection rates were 85.7% (12/14) in MSS ≥40 and 65.5% with MSS 30–39 but only 12.8% (6/47) for sporadic breast cancer. PV rates were low and divided equally betweenBRCA1/2andCHEK2.ConclusionAs expected,BRCA2PVs predominate in MBC families with rates 10-fold those inCHEK2andBRCA1. The MSS is an effective tool in assessing the likelihood ofBRCA1/2PVs.