Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.
Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.
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DOI：
10.1200/po.21.00249
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发表时间：
2021-11
影响因子：
4.6
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中科院分区：
文献类型：
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前期多基因小组检测(MGPT)的临床效用直接关系到筛查人群中致病变异(PV)的频率，以及如何将遗传结果用于指导治疗决策和癌症预防工作。MGPT对许多常见恶性肿瘤的益处仍有待确定。在这项研究中，我们评估了未选择的子宫内膜癌(EC)患者的预先MGPT，以确定癌症易感基因中PV的频率。从2017年10月1日到2020年12月31日，9家俄亥俄州机构前瞻性地登记了EC患者。对961例新诊断的食管癌患者进行了47个肿瘤易感基因的临床种系检测。除了估计生殖系PV的流行率外，还比较了MGPT和基于肿瘤的筛查中发现的Lynch综合征(LS)的个体数量。在961名妇女中，97人(10.1%)被确定为可能的致病变异或PV。961例患者中有29例(3%；95%CI，2.1~4.3)诊断为LS，以PMS2中PVs最多见。除了通过常规肿瘤筛查确定的20名患者外，MGPT还发现了9名LS患者。1%的患者(10/961；95%CI，0.6~1.9)发现BRCA1和BRCA2PV，该组患者的II型内皮细胞显著丰富。这项前瞻性的多中心研究显示，在10%未经选择的新诊断EC妇女中存在潜在的可操作的生殖系变异，支持对所有EC患者预先使用MGPT。BRCA1或BRCA2杂合子经常患有II型癌症的发现表明，患有侵袭性组织学EC亚型的女性有治疗机会。
Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.