Abstract
Simple SummaryIn 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.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.
Highlights
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related mortality in women worldwide [1]
Pathogenic variants were identified in two high-penetrance BC and Triple-negative breast cancer (TNBC) susceptibility genes, in 8 out of 163 patients tested (4.9%) (Table 1)
Two PALB2-positive patients did not have a family history of breast, ovarian, pancreatic, or colorectal cancer, whereas two other patients had a strong family history (Table 1)
Summary
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related mortality in women worldwide [1]. Triple-negative breast cancer (TNBC) is a distinct, highly aggressive form of BC, characterized by lack of expression of the estrogen and progesterone receptors (ER/PR) as well as of human epidermal growth factor receptor 2 (HER2) in breast tumors [2]. Survival rates are lower compared to other forms of breast cancer, with the majority of patients presenting with early recurrence and a high frequency of metastasis, especially to the central nervous system (20%) and viscera (29%) [3,6,7]. The five-year survival rate of patients with TNBC is estimated at 70%
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