Genetic features of breast cancer patients and women with a cancer-prone family history

Introduction . 5–10% of breast cancer (BC) cases are associated with germline pathogenic variants (PVs) in predisposition genes. In Russia, detection of “8 frequent” BRCA1,2 variants by PCR is recommended, with next generation sequensing (NGS) performed only at a second stage. Most studies on BC PVs have focused on BRCA1,2 , not exploring other candidate genes. Aim . Analyze the frequency and spectrum of PVs in candidate genes in patients with BC and healthy women with a family history of cancer. Materials and methods . Results of NGS testing (26-gene panel) on peripheral blood from 291 women were retrospectively analyzed. Participants were divided into 2 groups: 1 – patients with a history of BC (n = 146); 2 – women with 1 st /2 nd degree relatives diagnosed with BC or ovarian cancer (n = 145). Results . PVs were 2.5 times more frequent in Group 1 (21.2%) vs Group 2 (8.3%), р = 0,0012. BC onset with PVs occurred earlier than in women in whom significant genetic variants were not identified (39.3 ± 1 vs 44 ± 0,9 years, р = 0,01). PV in the BRCA1,2 genes were detected in 14.3% of group 1 and 6.2% of group 2, respectively. The most frequently detected variants were. BRCA1,2 PVs were most frequent (14.3% Grp1, 6.2% Grp2); Most common PVs were in BRCA1 : c.5266dupC, c.4035delA. BRCA1,2 PVs comprised only 68,18% of all PVs, confirming importance of testing other genes. CHEK2 PVs were frequent in Group 1 (4.8%), 7 times higher than Group 2 (р = 0,0076). CHEK2 :c.1100delC comprised 57% of these. 20.4% were VUS (variants of uncertain significance), often in non- BRCA genes. PVs in Group 2 were 8 times higher than general population rates. Conclusion . NGS enables detection of a full spectrum of clinically significant variants, requiring high expertise for interpretation.