Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer?

Purpose To characterize the spectrum ofBRCA1andBRCA2pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations. Methods Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation inBRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screenedBRCA1andBRCA2in the germline DNA of 426 women in total. Results We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants inBRCA1andBRCA2, respectively. We observed fiveBRCA1and eightBRCA2P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 inBRCA1and 10 inBRCA2). Conclusions These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.