Prevalence of recurrent and non-recurrent BRCA1 and BRCA2 pathogenic variants in Polish breast cancer patients: insights from a regional genetic testing cohort from Lower Silesia.

BACKGROUND: The prevalence and spectrum of pathogenic and likely pathogenic variants (PVs/LPVs) in BRCA1/2 vary across populations, necessitating region-specific analyses to identify recurrent and non-recurrent variants and to evaluate the effectiveness of current diagnostic strategies. Published experience remains dominated by North American and West-European or Nordic cohorts. To address this gap, we present the first comprehensive analysis of BRCA testing outcomes from Central Europe. METHODS: A next-generation sequencing (NGS) analysis of BRCA1/2 was performed in a regional cohort of 1,021 consecutive breast cancer patients from Lower Silesia (Poland), treated between March 2024 and April 2025. Clinical and pathological characteristics were compared between PV/LPV carriers and non-carriers. RESULTS: Nineteen distinct PVs/LPVs (11 in BRCA1 and 8 in BRCA2) were identified in 30 patients (2.94%; 95% CI: 2.07%–4.16%, Wilson). The most frequent variant was BRCA1 c.5266dup (30% of all variants), followed by c.181T > G (10%). Most variants (56.7%) were unique. No copy number variants were detected. Carriers were significantly younger at diagnosis (median 47 vs. 66 years; p < 0.0001) and exhibited a distinct tumor phenotype, including a markedly higher prevalence of triple-negative breast cancer (43.3% vs. 8.5%; OR = 8.24; p < 0.0001), lower ER/PR expression, higher Ki-67, larger tumor size, and more advanced stage at diagnosis (all p < 0.05). CONCLUSIONS: The prevalence of BRCA1/2 PVs/LPVs in this unselected Polish regional cohort was lower than previously reported, with a high proportion of non-recurrent variants. This Central European cohort demonstrates results consistent with international benchmarks. Our findings suggest limited effectiveness of founder mutation–based testing strategies and support the implementation of comprehensive NGS-based diagnostics in routine clinical practice to improve detection of clinically relevant variants and guide treatment decisions.