Abstract：
BACKGROUND: Recently, genes involved in homologous recombination repair (HRR) pathway have been extensively studied. However, the landscapes of HRR gene mutations remain poorly defined in Chinese high-risk breast cancer (BC) patients. Our study aims to identify the status of germline and somatic HRR gene mutations and their association with clinicopathological features in these patients.
METHODS: A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis.
RESULTS: Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05).
CONCLUSIONS: The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.
METHODS: A total of 100 high-risk BC patients from our institution who underwent paired peripheral blood germline and BC tissues somatic 26 genes next-generation sequencing (NGS) from January 2018 to July 2023 were enrolled for retrospective analysis.
RESULTS: Out of 100 high-risk BC patients, 55 (55%) had at least one germline or somatic mutation in HRR genes. Among them, 22% carried germline pathogenic variants (19 BRCA1/2 and 3 non-BRCA genes), 9% harbored somatic pathogenic mutations (3 BRCA1/2 and 6 non-BRCA genes). Among high-risk factors, family history and early onset BC showed a correlation with HRR gene mutations (p < 0.05). BRCA1 germline and HRR gene somatic mutations showed a correlation with TNBC, but BRCA2 germline mutations were associated with Luminal B/HER2-negative BC (p < 0.05). Patients with HRR gene somatic pathogenic variant more likely had a lympho-vascular invasion and distant metastasis (p < 0.05).
CONCLUSIONS: The prevalence of HRR gene germline and somatic mutations were higher in Chinese BC patients with high risk factors. We strongly recommend that these high-risk BC patients receive comprehensive gene mutation testing, especially HRR genes, which are not only related to genetic consultation for BC patients and provide a theoretical basis for necessary prevention and individualized treatment.
摘要：
背景：最近，同源重组修复（HRR）途径中涉及的基因已被广泛研究。然而,在中国高危乳腺癌(BC)患者中,HRR基因突变的景观仍然不明确.我们的研究旨在确定这些患者种系和体细胞HRR基因突变的状态及其与临床病理特征的关系。
方法：纳入我院于2018年1月至2023年7月接受配对外周血种系和BC组织体细胞26基因下一代测序（NGS）的100例高危BC患者进行回顾性分析。
结果：在100例高危BC患者中，55（55％）在HRR基因中至少有一个种系或体细胞突变。其中,22％携带种系致病变异（19个BRCA1/2和3个非BRCA基因），9%有体细胞致病性突变(3个BRCA1/2和6个非BRCA基因)。在高风险因素中，家族史和早发性BC与HRR基因突变相关(p<0.05)。BRCA1种系和HRR基因体细胞突变与TNBC,但BRCA2种系突变与LuminalB/HER2阴性BC相关(p<0.05)。具有HRR基因体细胞致病变异的患者更有可能发生淋巴血管浸润和远处转移（p<0.05）。
结论：在具有高危因素的中国BC患者中，HRR基因种系和体细胞突变的患病率较高。我们强烈建议这些高危BC患者接受全面的基因突变检测，尤其是HRR基因，这不仅关系到BC患者的遗传咨询,而且为必要的预防和个体化治疗提供了理论依据。
方法：纳入我院于2018年1月至2023年7月接受配对外周血种系和BC组织体细胞26基因下一代测序（NGS）的100例高危BC患者进行回顾性分析。
结果：在100例高危BC患者中，55（55％）在HRR基因中至少有一个种系或体细胞突变。其中,22％携带种系致病变异（19个BRCA1/2和3个非BRCA基因），9%有体细胞致病性突变(3个BRCA1/2和6个非BRCA基因)。在高风险因素中，家族史和早发性BC与HRR基因突变相关(p<0.05)。BRCA1种系和HRR基因体细胞突变与TNBC,但BRCA2种系突变与LuminalB/HER2阴性BC相关(p<0.05)。具有HRR基因体细胞致病变异的患者更有可能发生淋巴血管浸润和远处转移（p<0.05）。
结论：在具有高危因素的中国BC患者中，HRR基因种系和体细胞突变的患病率较高。我们强烈建议这些高危BC患者接受全面的基因突变检测，尤其是HRR基因，这不仅关系到BC患者的遗传咨询,而且为必要的预防和个体化治疗提供了理论依据。
