估计有10%的乳腺癌和卵巢癌是由遗传原因引起的。乳腺癌患者种系易感性基因的当前测试指南已开发出来,以鉴定BRCA1/2变体的携带者,并且在小组测试时代已经发展。我们评估了国家综合癌症网络(NCCN)指南在扩展面板测试中识别具有致病变异的乳腺癌患者的能力。
一个机构审查委员会批准的多中心前瞻性注册是由20个社区和学术网站在癌症基因检测和咨询方面经验丰富。合格标准包括先前或新诊断的乳腺癌患者,他们没有接受单基因或多基因检测。连续18至90岁的患者获得同意,并接受了80基因小组测试。符合健康保险可移植性和责任法案的电子病例报告表格收集了患者人口统计信息,诊断,表型,和测试结果。
招募了1000多名患者,分析了959例患者的数据记录;49.95%符合NCCN标准,50.05%没有。总的来说,8.65%的患者具有致病性/可能致病性(P/LP)变异。在符合NCCN指南的测试结果的患者中,9.39%有P/LP变异。在不符合指南的患者中,7.9%有P/LP变异。这些组之间的阳性结果差异无统计学意义(Fisher精确检验P=0.4241)。
我们的结果表明,目前的测试指南错过了将近一半的具有临床可操作和/或管理指南的P/LP变异的乳腺癌患者。我们建议所有诊断为乳腺癌的患者都接受扩大的小组检查。
An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing
guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN)
guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing.
An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results.
More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN
guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet
guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher\'s exact test P = .4241).
Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing
guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.