该对哪些乳腺癌女性进行遗传基因检测

　　美国国家综合癌症网络（NCCN）遗传性或家族性癌症检测指南仅推荐对有家族史等高风险女性进行遗传基因检测，而美国乳腺外科医师学会（ASBrS）指南推荐对所有女性进行遗传基因检测。

　　2020年3月3日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表梅奥医学中心、宾夕法尼亚大学的研究报告，对乳腺癌女性遗传致病变异检测标准进行了单中心评价。

　　该研究对2000年5月15日～2016年5月31日梅奥医学中心乳腺癌登记数据库3907例乳腺癌女性9种乳腺癌易感基因（ATM、BRCA1、BRCA2、CDH1、CHEK2、NF1、PALB2、PTEN、TP53）进行回顾分析，对NCCN标准与ASBrS标准的灵敏度（真阳性率）和特异度（真阴性率）进行比较。

　　结果，1872例（47.9%）符合NCCN标准与2035例（52.1%）不符合NCCN标准的女性相比，携带9种易感基因致病变异的比例显著较高（9.0%比3.5%，P<0.001）。

　　对于不符合NCCN标准的女性，其中14例（0.7%）携带BRCA1或BRCA2致病变异。

　　NCCN标准对于9种易感基因的灵敏度为70.1%、特异度为53.5%，对于BRCA1和BRCA2的灵敏度为86.9%、特异度为53.2%。

　　将NCCN标准扩展至所有年龄≤65岁时被诊断为乳腺癌女性，对于9种易感基因的灵敏度达92.1%、特异度为22.0%，对于BRCA1和BRCA2的灵敏度达98.1%、特异度为21.7%。

　　因此，该单中心研究结果表明，相当一部分乳腺癌患者虽然携带易感基因遗传致病变异，但是不符合NCCN标准。将NCCN标准扩展至所有年龄≤65岁时被诊断为乳腺癌女性，可以提高选择标准的灵敏度，而无需对所有乳腺癌女性进行检测。

J Clin Oncol. 2020 Mar 3. [Epub ahead of print]

Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.

Yadav S, Hu C, Hart SN, Boddicker N, Polley EC, Na J, Gnanaolivu R, Lee KY, Lindstrom T, Armasu S, Fitz-Gibbon P, Ghosh K, Stan DL, Pruthi S, Neal L, Sandhu N, Rhodes DJ, Klassen C, Peethambaram PP, Haddad TC, Olson JE, Hoskin TL, Goetz MP, Domchek SM, Boughey JC, Ruddy KJ, Couch FJ.

Mayo Clinic, Rochester, MN; University of Pennsylvania, Philadelphia, PA.

PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer.

MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons.

RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < 0.001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2.

CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

PMID: 32125938

DOI: 10.1200/JCO.19.02190