Scholarlink

Background <p>The prevalence and spectrum of pathogenic and likely pathogenic variants (PVs/LPVs) in <i>BRCA1/2</i> 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 <i>BRCA</i> testing outcomes from Central Europe.</p> Methods <p>A next-generation sequencing (NGS) analysis of <i>BRCA1/2</i> 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.</p> Results <p>Nineteen distinct PVs/LPVs (11 in <i>BRCA1</i> and 8 in <i>BRCA2</i>) were identified in 30 patients (2.94%; 95% CI: 2.07%–4.16%, Wilson). The most frequent variant was <i>BRCA1</i> c.5266dup (30% of all variants), followed by c.181T &gt; 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; <i>p</i> &lt; 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; <i>p</i> &lt; 0.0001), lower ER/PR expression, higher Ki-67, larger tumor size, and more advanced stage at diagnosis (all <i>p</i> &lt; 0.05).</p> Conclusions <p>The prevalence of <i>BRCA1/2</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

查看全文
  • Rafal Matkowski,
  • Mariola Abrahamowska,
  • Dagmara Michalowska,
  • Agnieszka Chrusciel,
  • Jolanta Szelachowska,
  • Dorota Blomka,
  • Paulina Lawicka,
  • Ewelina Czykalko,
  • Aleksandra Pietron,
  • Marcin Ekiert,
  • Anna Doraczynska-Kowalik,
  • Gabriela Janus-Szymanska,
  • Piotr Kasprzak,
  • Bartlomiej Szynglarewicz,
  • Izabela Laczmanska

摘要

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.