Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Duke Cancer Institute, Duke University, Durham, NC, USA.
Ann Surg Oncol. 2020 Oct;27(10):3633-3640. doi: 10.1245/s10434-020-08480-z. Epub 2020 Jun 5.
A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT.
We performed an 11-institution review of contemporary (2007-2017) PT practice. We recorded multigenerational family history and personal history of genetic testing. We identified patients meeting NCCN criteria for genetic evaluation. Logistic regression estimated the association of select covariates with likelihood of undergoing genetic testing.
Of 550 PT patients, 59.8% (n = 329) had a close family history of cancer, and 34.0% (n = 112) had ≥ 3 family members affected. Only 6.2% (n = 34) underwent genetic testing, 38.2% (n = 13) of whom had only BRCA1/BRCA2 tested. Of 34 patients tested, 8.8% had a deleterious mutation (1 BRCA1, 2 TP53), and 5.9% had a BRCA2 VUS. Of women who had TP53 testing (N = 21), 9.5% had a mutation. Selection for testing was not associated with age (odds ratio [OR] 1.01, p = 0.55) or PT size (p = 0.12) but was associated with grade (malignant vs. benign: OR 9.17, 95% CI 3.97-21.18) and meeting NCCN criteria (OR 3.43, 95% confidence interval 1.70-6.94). Notably, an additional 86 (15.6%) patients met NCCN criteria but had no genetic testing.
Very few women with PT undergo germline testing; however, in those selected for testing, a deleterious mutation was identified in ~ 10%. Multigene testing of a PT cohort would present an opportunity to discover the true incidence of germline mutations in PT patients.
目前关于叶状肿瘤（PT）相关遗传突变的数据很少；然而，已经有一些报道（TP53、BRCA1 和 RB1）。PT 诊断不符合 NCCN 检测标准，包括 Li-Fraumeni 综合征（TP53）。我们试图确定与 PT 相关的突变的流行率。
我们对 11 个机构的当代（2007-2017 年）PT 实践进行了回顾。我们记录了多代家族史和个人遗传检测史。我们确定了符合 NCCN 遗传评估标准的患者。逻辑回归估计了选择的协变量与接受遗传检测可能性的关联。
在 550 名 PT 患者中，59.8%（n=329）有近亲患癌症的家族史，34.0%（n=112）有≥3 名家庭成员患病。只有 6.2%（n=34）接受了基因检测，其中 38.2%（n=13）仅检测了 BRCA1/BRCA2。在 34 名接受检测的患者中，8.8%（n=3）有有害突变（1 例 BRCA1，2 例 TP53），5.9%（n=2）有 BRCA2 VUS。在接受 TP53 检测的女性中（n=21），9.5%（n=2）有突变。检测的选择与年龄（比值比[OR]1.01，p=0.55）或 PT 大小（p=0.12）无关，但与分级（恶性与良性：OR 9.17，95%CI 3.97-21.18）和符合 NCCN 标准（OR 3.43，95%置信区间 1.70-6.94）有关。值得注意的是，另外 86 名（15.6%）符合 NCCN 标准但未进行基因检测的患者。
很少有 PT 患者接受种系检测；然而，在选择接受检测的患者中，约 10%发现了有害突变。对 PT 患者进行多基因检测将有机会发现 PT 患者种系突变的真实发生率。
