Different association of gBRCA1 and gBRCA2 variants with HER2-low status in invasive breast cancer: findings from a Ukrainian study.

HER2-low breast cancer (BC) representing about 40-55% of all BC has emerged as a targetable entity. However, little is known about the link between germline BRCA1/2 mutations (gBRCA1/2) and HER2-low status in BC, especially in Ukrainian population. This study aims to elaborate on the rates of HER2-low status among patients with sporadic and BRCA1/2-associated hereditary BC in the Ukrainian population and investigate the relationship between gBRCA1/2 and HER2 status. This was a retrospective multicenter cross-sectional study on 1412 cases of BC. HER2 status was assessed according to ASCO-CAP Guidelines. All patients underwent germline NGS testing to detect SNV and indel variants in BRCA1 and BRCA2 genes. Overall, gBRCA1/2 genetic variants were found in 212 (15.0%) patients with BC. gBRCA1 variants were associated mostly with TNBC molecular subtype, while gBRCA2 mutations were linked to Luminal-like BC. The majority (343 of 436; 78.7%) of HER2-low BC was associated with luminal-like BC (P < 0.001). We also found significant relationships between gBRCA1/2 and HER2 status (P = 0.006). There were 837 HER2-zero (59.3%), 436 HER2-low (30.9%) and 139 HER2-positive (9.8%) BC. More than 70% of patients with gBRCA1 were HER2-negative. Alternatively, gBRCA2 cases possessed a higher rate of HER-low BC status (37.5%) as compared to WT (31.2%) and gBRCA1-associated BC (25.7%). In conclusion, gBRCA1 and gBRCA2 variants differed in their association with breast carcinoma molecular subtype and HER2-low status. gBRCA1 variants were linked to the prevalence of TNBC type and HER2 zero status. In contrast, gBRCA2 cases had a higher rate of HR + and HER-low breast cancer.