Chan Soon-Shiong Institute of Molecular Medicine at Windber, 620 Seventh Street, Windber, PA, 15963, USA.
Murtha Cancer Center/Research Program, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA.
Fam Cancer. 2021 Jul;20(3):181-187. doi: 10.1007/s10689-020-00213-1. Epub 2020 Oct 21.
African American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project. National Comprehensive Cancer Network (NCCN) Hereditary Cancer testing criteria version 1.2020 were applied to determine genetic risk. Targeted sequencing was performed using the TruSight Cancer panel and variants classified using the ClinVar database. Using NCCN criteria, 64.1% of African American women would be eligible for genetic testing. Fifty pathogenic or likely pathogenic mutations were detected in 19 genes with the highest frequencies in BRCA2 (29.4%) and BRCA1 (15.7%). Mutation frequencies in test-eligible and test-ineligible women were 13.1% and 3.5%, respectively. One-third of women harbored variants that could not be classified. While these data do not suggest a need to expand current commercial gene panels, NCCN criteria would fail to identify 12.5% of African American women with mutations in hereditary cancer predisposing genes.
非裔美国女性被诊断出患有乳腺癌的年龄较小，且患有三阴性乳腺癌的风险增加，这两个因素都包含在当前确定可能受益于基因检测的女性的指南中。商业乳腺癌易感性基因检测面板主要基于源自欧洲裔女性的数据，可能无法捕获与非裔美国女性乳腺癌相关的全部癌症易感性基因。在 2001 年至 2018 年期间，488 名未经选择的患有浸润性乳腺癌的非裔美国女性参加了临床乳房保健项目。国家综合癌症网络 (NCCN) 遗传性癌症检测标准版本 1.2020 被用于确定遗传风险。使用 TruSight 癌症面板进行靶向测序，并使用 ClinVar 数据库对变体进行分类。使用 NCCN 标准，64.1%的非裔美国女性有资格进行基因检测。在 19 个基因中检测到了 50 个致病性或可能致病性的突变，BRCA2（29.4%）和 BRCA1（15.7%）的突变频率最高。在符合检测条件和不符合检测条件的女性中，突变频率分别为 13.1%和 3.5%。三分之一的女性携带无法分类的变异。虽然这些数据表明不需要扩大当前的商业基因面板，但 NCCN 标准将无法识别出 12.5%的携带遗传性癌症易感基因突变的非裔美国女性。
