Rosenberger Laura H, Thomas Samantha M, Hieken Tina J, Gallagher Kristalyn K, Spanheimer Philip M, Neuman Heather B, Weiss Anna C, King Tari A, Wong Jasmine, Tong Barry S, Nash Amanda L, Frazier Margaret Powell, Menendez Carolyn S, Hwang E Shelley, Jakub James W, Plichta Jennifer K
Department of Surgery, Duke University Medical Center, DUMC 3513, Durham, NC, 27710, USA.
Duke Cancer Institute, Duke University, Durham, NC, USA.
Breast Cancer Res Treat. 2025 Jan;209(2):275-282. doi: 10.1007/s10549-024-07488-3. Epub 2024 Sep 13.
Germline genetic mutations in women with phyllodes tumors (PT) are understudied, although some describe associations of PT with various mutations. We sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in women with PT.
A 6-site multi-center study of women with a PT was initiated, then expanded nationally through an online "Phyllodes Support Group." All women underwent 84-gene panel testing. We defined eligibility for testing based on select NCCN (National Comprehensive Cancer Network) criteria (v1.2022). Logistic regression was used to estimate the association of covariates with the likelihood of a P/LP variant.
274 women were enrolled: 164 (59.9%) through multi-center recruitment and 110 (40.1%) via online recruitment. 248 women completed testing; overall 14.1% (N = 35) had a P/LP variant, and over half (N = 19) of these individuals had a mutation in genes associated with autosomal dominant (AD) cancer conditions. The most common AD genes with a P/LP variant included CHEK2, ATM, and RAD51D. A quarter of participants (23.8%) met NCCN criteria for testing, but we found no difference in prevalence of a P/LP variant based on eligibility (p = 0.54). After adjustment, the presence of P/LP variants was not associated with age, NCCN testing eligibility, or PT type (all p > 0.05).
Our study demonstrates that 7.7% of women with PT harbor germline P/LP variants in genes associated with AD cancer conditions. Early identification of these variants has implications for screening, risk reduction, and/or treatment. National guidelines for women with PT do not currently address germline genetic testing, which could be considered.
叶状肿瘤（PT）女性患者的胚系基因突变研究较少，尽管有研究描述了PT与各种突变之间的关联。我们试图确定PT女性患者中致病/可能致病（P/LP）变异的发生率。
启动了一项针对PT女性患者的6个位点的多中心研究，然后通过在线“叶状肿瘤支持小组”在全国范围内扩大研究。所有女性均接受了84基因检测。我们根据美国国立综合癌症网络（NCCN）的特定标准（v1.2022）定义检测资格。采用逻辑回归分析来估计协变量与P/LP变异可能性之间的关联。
共纳入274名女性：164名（59.9%）通过多中心招募，110名（40.1%）通过在线招募。248名女性完成检测；总体而言，14.1%（N = 35）有P/LP变异，其中超过一半（N = 19）的个体在与常染色体显性（AD）癌症相关的基因中有突变。具有P/LP变异的最常见AD基因包括CHEK2、ATM和RAD51D。四分之一的参与者（23.8%）符合NCCN检测标准，但我们发现基于检测资格的P/LP变异发生率没有差异（p = 0.54）。调整后，P/LP变异的存在与年龄、NCCN检测资格或PT类型均无关联（所有p>0.05）。
我们的研究表明，7.7%的PT女性患者在与AD癌症相关的基因中携带胚系P/LP变异。这些变异的早期识别对筛查、降低风险和/或治疗具有重要意义。目前，针对PT女性患者的国家指南未涉及胚系基因检测，这一点值得考虑。
