Reason Ellery H, Aiduk Michael D, Nash Amanda L, McDuff Susan G R, Renner Derrick, Kollipara Rahul Krishna, Satta Sandro, Velichko Sharlene, Kalashnikova Ekaterina, Rodriguez Angel A, Liu Minetta C, Strickler John H, Grilley-Olson Juneko E, Rosenberger Laura H
Duke University School of Medicine, Durham, NC, USA.
Duke Cancer Institute, Duke University, Durham, NC, USA.
Ann Surg Oncol. 2025 Jul 23. doi: 10.1245/s10434-025-17851-3.
Malignant phyllodes tumors (MPT) are biologically aggressive breast neoplasms, with high local and distant recurrence rates and a median survival of 12 months when metastatic. With a disease-free interval often less than 2 years, circulating tumor DNA (ctDNA) may allow for earlier identification of patients with MPT at risk for recurrence. Here, we aim to determine the feasibility of detecting ctDNA in (1) patients with known, active metastatic disease and (2) patients with nonmetastatic MPT prior to surgical resection.
Nine patients with MPT were identified from an institutional review board-approved prospective phyllodes tumors registry and tumor biorepository. Whole exome sequencing (WES) was performed on tumor tissue and matched blood samples for each patient. A tumor informed assay with 16 patient-specific somatic variants was used to detect ctDNA in corresponding plasma samples.
Of the nine patients included (median age: 48.0 years), 67% (n = 6) had known untreated metastatic disease, and 33% (n = 3) did not have metastatic disease at the time of tissue collection. All patients (n = 6/6) with metastatic disease had detectable ctDNA (mean 119 mean tumor molecules (MTM)/mL). Furthermore, 33% (n = 1/3) of nonmetastatic patients had detectable ctDNA (mean 0.2 MTM/mL) before definitive surgery. The most common mutations revealed by tumor WES were in TERT, TP53, and NF1.
ctDNA is reliably detected in patients with known metastatic disease and may enable monitoring for distant relapses after primary surgical resection. These data will inform a prospective study design to determine the efficacy and utility of ctDNA for MPT as well as its potential for monitoring response to systemic therapies.
恶性叶状肿瘤（MPT）是具有生物学侵袭性的乳腺肿瘤，局部和远处复发率高，发生转移时的中位生存期为12个月。由于无病间期通常少于2年，循环肿瘤DNA（ctDNA）可能有助于更早识别有MPT复发风险的患者。在此，我们旨在确定在（1）已知患有活动性转移性疾病的患者和（2）手术切除前的非转移性MPT患者中检测ctDNA的可行性。
从机构审查委员会批准的前瞻性叶状肿瘤登记处和肿瘤生物样本库中识别出9例MPT患者。对每位患者的肿瘤组织和匹配的血液样本进行全外显子组测序（WES）。使用包含16个患者特异性体细胞变异的肿瘤知情检测法检测相应血浆样本中的ctDNA。
纳入的9例患者（中位年龄：48.0岁）中，67%（n = 6）已知患有未经治疗的转移性疾病，33%（n = 3）在采集组织时无转移性疾病。所有患有转移性疾病的患者（n = 6/6）均可检测到ctDNA（平均119个平均肿瘤分子（MTM）/mL）。此外，33%（n = 1/3）的非转移性患者在确定性手术前可检测到ctDNA（平均0.2 MTM/mL）。肿瘤WES揭示的最常见突变位于TERT、TP53和NF1基因。
在已知患有转移性疾病的患者中可可靠检测到ctDNA，这可能有助于在初次手术切除后监测远处复发。这些数据将为一项前瞻性研究设计提供信息，以确定ctDNA对MPT的疗效和实用性及其监测全身治疗反应的潜力。
