Lu Kit, Smith Meagan, Kanderi Tejaswi, Verbiar Julia, Laspe Jennifer, Bair Latesha, Torp Lisa
Medical Oncology, University of Pittsburgh Medical Center Hillman Cancer Center, Harrisburg, USA.
Genetics, University of Pittsburgh Medical Center Hillman Cancer Center, Harrisburg, USA.
Cureus. 2021 Apr 22;13(4):e14637. doi: 10.7759/cureus.14637.
Background Breast cancer is the second leading cause of cancer death in women. There are multiple pathogenic mutations in addition to BRCA1/2 that are implicated in causing hereditary breast cancer. Methods and results We conducted a retrospective analysis of 1568 patients with breast cancer diagnosed between January 1, 2015, and December 31, 2018. The age range is 23-87. Among the study population, 26% had genetic testing and 8% of those were found to carry a pathogenic variant, as designated in NCCN (National Comprehensive Cancer Network) Guidelines. Of that 8%, 3.4% were BRCA1 and BRCA2 mutations, and the rest were other prevalent pathogenic variants. Discussion Expanded panel testing has the potential to increase the detection rate of pathogenic variants compared to testing for BRCA1/2 alone. Diagnostic accuracy of genetic causes of breast cancer has a significant clinical impact on patients and their families in terms of targeted treatment and prevention strategies. There is a strong need for further understanding of genetic patterns and variations in hereditary breast cancer. Awareness of the possibility of moderate to low penetrance genes and variants of uncertain significance (VUS) is important to assist with appropriate genetic counseling. We believe that physicians should consider re-testing with an expanded panel if patients previously had BRCA1 and BRCA2 testings only with a negative result as it may identify additional mutations.
乳腺癌是女性癌症死亡的第二大主要原因。除BRCA1/2外，还有多种致病突变与遗传性乳腺癌的发生有关。
我们对2015年1月1日至2018年12月31日期间确诊的1568例乳腺癌患者进行了回顾性分析。年龄范围为23 - 87岁。在研究人群中，26%进行了基因检测，其中8%被发现携带NCCN（美国国立综合癌症网络）指南中指定的致病变异。在这8%中，3.4%是BRCA1和BRCA2突变，其余是其他常见的致病变异。
与仅检测BRCA1/2相比，扩展检测 panel 有可能提高致病变异的检出率。乳腺癌遗传病因的诊断准确性在靶向治疗和预防策略方面对患者及其家庭具有重大临床影响。迫切需要进一步了解遗传性乳腺癌的基因模式和变异。认识到中度至低度 penetrance 基因和意义未明变异（VUS）的可能性对于协助进行适当的遗传咨询很重要。我们认为，如果患者之前仅进行了BRCA1和BRCA2检测且结果为阴性，医生应考虑使用扩展检测 panel 进行重新检测，因为这可能会识别出其他突变。
