NGS Panel Testing of Triple-Negative Breast Cancer Patients in Cyprus: A Study of BRCA-Negative Cases

SIMPLE SUMMARY: In Cyprus, approximately 9% of triple-negative (negative in common breast cancer receptors—estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors) breast cancer (TNBC) patients carry inherited mutations in the BRCA1/2 breast cancer (BC) susceptibility genes. These mutations increase the risk of BC. However, the contribution of other BC susceptibility genes has not yet been determined. To this end, we aimed to investigate the prevalence of mutations in BRCA1/2-negative TNBC patients in Cyprus. Ninety-five cancer susceptibility genes were sequenced for 163 TNBC patients. The frequency of non-BRCA mutations and especially PALB2 in TNBC patients in Cyprus appears to be higher compared to other populations, and half of the mutation-positive patients were diagnosed over the age of 60 years. Based on these results, we believe that PALB2 and TP53 along with BRCA1/2 genetic testing could be beneficial for a large proportion of TNBC patients in Cyprus, irrespective of their age of diagnosis. ABSTRACT: In Cyprus, approximately 9% of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer (TNBC) patients are positive for germline pathogenic variants (PVs) in BRCA1/2. However, the contribution of other genes has not yet been determined. To this end, we aimed to investigate the prevalence of germline PVs in BRCA1/2-negative TNBC patients in Cyprus, unselected for family history of cancer or age of diagnosis. A comprehensive 94-cancer-gene panel was implemented for 163 germline DNA samples, extracted from the peripheral blood of TNBC patients. Identified variants of uncertain clinical significance were evaluated, using extensive in silico investigation. Eight PVs (4.9%) were identified in two high-penetrance TNBC susceptibility genes. Of these, seven occurred in PALB2 (87.5%) and one occurred in TP53 (12.5%). Interestingly, 50% of the patients carrying PVs were diagnosed over the age of 60 years. The frequency of non-BRCA PVs (4.9%) and especially PALB2 PVs (4.3%) in TNBC patients in Cyprus appears to be higher compared to other populations. Based on these results, we believe that PALB2 and TP53 along with BRCA1/2 genetic testing could be beneficial for a large proportion of TNBC patients in Cyprus, irrespective of their age of diagnosis.