Zafar Maha, Krishnakumar Manaswini, Reddy Aswanth
Department of Internal Medicine, Mercy Hospital Fort Smith, Fort Smith, AR, USA.
Department of Internal Medicine, Arkansas College of Osteopathic Medicine Mercy Program, Fort Smith, AR, USA.
J Cancer Prev. 2025 Mar 30;30(1):41-46. doi: 10.15430/JCP.25.001.
Breast cancer is the most common cancer among women worldwide, with germline mutations in high-penetrance genes like BRCA1 and BRCA2, and moderate-penetrance genes such as CHEK2 and ATM contributing majorly to the onset of the same. Universal germline genetic testing offers an avenue to improve early identification and develop appropriate management guidelines. Our retrospective cohort study analyzed data from 525 newly diagnosed breast cancer patients at Mercy Hospital Fort Smith from January 2020 to December 2023. Patients underwent germline genetic testing using next-generation sequencing panels irrespective of family history of cancer. Details on patient demographics, clinical characteristics, and genetic test results were collected and analyzed. The median age at diagnosis of patients was 66, with invasive ductal carcinoma (IDC) being the major subtype (66%). CHEK2 mutations were the most common pathogenic mutations (9 patients), followed by BRCA1 and MUTYH (6 each). Pathogenic mutations were more prevalent in patients over 60 years (63%). Germline mutations were identified more frequently in IDC than in ductal carcinoma in situ. Among patients with germline mutations, there was a significant drift toward mastectomy over breast-conserving surgery. Universal germline genetic testing identified pathogenic mutations in a significant proportion of breast cancer patients, especially among the older patient population. The findings further emphasize the importance of integrating universal genetic testing into routine care to guide surgical and risk-reduction management protocols effectively. Further research is needed to regularize genetic testing in similar patients.
乳腺癌是全球女性中最常见的癌症，胚系突变存在于高外显率基因如BRCA1和BRCA2以及中低外显率基因如CHEK2和ATM中，这些基因在很大程度上导致了乳腺癌的发病。全面的胚系基因检测为改善早期识别和制定适当的管理指南提供了一条途径。我们的回顾性队列研究分析了2020年1月至2023年12月在史密斯堡仁慈医院新诊断的525例乳腺癌患者的数据。无论癌症家族史如何，患者均使用下一代测序平台进行胚系基因检测。收集并分析了患者人口统计学、临床特征和基因检测结果的详细信息。患者诊断时的中位年龄为66岁，浸润性导管癌（IDC）是主要亚型（66%）。CHEK2突变是最常见的致病突变（9例），其次是BRCA1和MUTYH（各6例）。致病突变在60岁以上患者中更为普遍（63%）。胚系突变在IDC中比原位导管癌中更常见。在有胚系突变的患者中，与保乳手术相比，乳房切除术有明显增加的趋势。全面的胚系基因检测在很大比例的乳腺癌患者中发现了致病突变，尤其是在老年患者群体中。这些发现进一步强调了将全面基因检测纳入常规护理以有效指导手术和降低风险管理方案的重要性。需要进一步研究以规范对类似患者的基因检测。
