FREQUENCY OF DELETERIOUS GERMLINE VARIANTS IN HER-2 LOW BREAST CANCER PATIENTS USING A HEREDITARY MULTI-PANEL GENE TESTING

Introduction: Around 10% of Breast Cancer (BC) are linked to genetic predisposition. Recently, Trastuzumab-Deruxtecan showed efficacy among patients with HER2-Low (i.e. HER2 with IHQ 1+, or 2+ with FISH negative). In HER2-Low breast cancer the prevalence of deleterious germline variants is not well characterized. Aim We aim to describe the frequency and clinical characteristics of deleterious germline variants in HER-2 Low BC patients tested with a germline multigene panel test (MGPT) and compare it with overall patients. Methods: We analyzed retrospectively results from patients with BC that performed a MGPT (20 to 145 genes) treated at a private hospital in Sao Paulo, Brazil, between 2018-2019. We compared the findings of patients with HER2-Low BC with overall BC population evaluated in the period. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Results: We evaluated 167 Brazilian BC patients who underwent MGPT. There were 79 HR positive, 38 HER2-positive and 27 TN. The median age was 45.8 years. There were 75 stage I, 62 stage II, 20 stage III, and 10 stage IV. In HER2-Low BC, 27 patients were HR positive and 7 negative. Median age for HER2-Low group was 45 years, and there were 19 stage I, 12 stage II, 3 stage III, and none stage IV. Pathogenic or likely pathogenic variant (PGV or LPGV) was found in 33 patients overall, as described: 7 BRCA1, 4 BRCA2, 2 ATM, 1 ATR, 2 CFTR, 3 CHEK2, 1 FANCA, 1 MERTK, 1 MLH1, 3 MUTYH, 1 RAD50, 3 RAD51, 1 RECQL4, and 2 TP53 mutations. In HER2-Low, a PGV or LPGV was identified in 26.5 % of the patients, meanwhile the incidence in overall cohort was 19.8 %. HER-2 Low patients were not related to a higher or lower incidence of deleterious variant (p= 0.17). No statistical differences were identified in prevalence of mutations in BRCA1/2 or homologous recombinant repair genes (p=0.9). Furthermore, no statistical significance was observed in clinical characteristics including age, histological type, tumor grade or ki67 in patients with HER-2 Low comparing to overall cohort. Conclusion: HER-2 Low breast cancer patients does not seem to have a different patterns or incidence of germline genetic findings compared to overall breast cancer population. Additionally, similar alterations in BRCA1/2 and homologous recombinant deficient genes in this subgroup of patients were observed compared to overall cohort.