Bader Gilbert, Quintanilha Julia C F, Veney Deloris, Graf Ryon P, Levy Mia, Pasquina Lincoln W, Stover Daniel G
The Ohio State University, Columbus, OH, USA.
Foundation Medicine, Inc., Boston, MA, USA.
Breast Cancer Res Treat. 2025 May 30. doi: 10.1007/s10549-025-07740-4.
Bone metastases develop in 50-70% of patients with metastatic breast cancer (MBC), with around one-third having bone as only site of distant disease (bone-only [BO]). Standard imaging is frequently insufficient to track bone metastases. Evidence suggests that circulating tumor DNA (ctDNA) tumor fraction (TF) is prognostic in MBC. We hypothesized that TF would be detectable and prognostic for BO-MBC.
MBC patients who underwent FoundationOne LiquidCDX comprehensive genomic profiling within 60 days before starting therapy were included. Clinical data was obtained from the nationwide deidentified Flatiron Health/Foundation Medicine Clinico-Genomic Database between 01/2011 and 12/2023.
We identified 778 patients for inclusion: 299 TF < 1% (TF-low), 175 TF 1-10% (TF-intermediate [int]), 304 TF > 10% (TF-high). Of these, 155 had BO-MBC, 622 had non-BO MBC (1 missing metastasis data). Among samples collected prior to first-line therapy (n = 256), there was no significant difference in the proportion of patients with detectable ctDNA comparing BO-MBC to non-BO MBC patients (P = 1.0). TF was prognostic among patients with BO-MBC: TF-low demonstrated more favorable real-world overall survival (rwOS) relative to TF-int (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.1-4.35) and TF-high (HR 2.07, 95% CI 1.12-3.82; log-rank P = 0.027). Multivariable analyses confirmed the independent and additive association of TF and less favorable rwOS. In multivariable analyses evaluating clinicopathologic factors associated with TF, non-BO metastases were not associated with higher ctDNA TF.
BO-MBC patients are as likely as non-BO-MBC to have detectable ctDNA and TF remains prognostic among BO-MBC patients, with TF < 1% associated with significantly better prognosis.
50%-70%的转移性乳腺癌（MBC）患者会发生骨转移，其中约三分之一患者的远处转移仅发生在骨（仅骨转移[BO]）。标准影像学检查往往不足以追踪骨转移情况。有证据表明，循环肿瘤DNA（ctDNA）肿瘤分数（TF）对MBC具有预后价值。我们假设TF在BO-MBC中是可检测的且具有预后价值。
纳入在开始治疗前60天内接受FoundationOne LiquidCDX综合基因组分析的MBC患者。临床数据来自2011年1月至2023年12月全国性的匿名Flatiron Health/Foundation Medicine临床基因组数据库。
我们确定了778例纳入患者：299例TF＜1%（低TF），175例TF为1%-10%（中等TF[int]），304例TF＞10%（高TF）。其中，155例为BO-MBC，622例为非BO-MBC（1例转移数据缺失）。在一线治疗前采集的样本（n = 256）中，BO-MBC患者与非BO-MBC患者中可检测到ctDNA的患者比例无显著差异（P = 1.0）。TF在BO-MBC患者中具有预后价值：低TF组相对于中等TF组显示出更有利的真实世界总生存期（rwOS）（风险比[HR] 2.19，95%置信区间[CI] 1.1-4.35）和高TF组（HR 2.07，95% CI 1.12-3.82；对数秩P = 0.027）。多变量分析证实了TF与较差rwOS之间的独立和相加关联。在评估与TF相关的临床病理因素的多变量分析中，非BO转移与较高的ctDNA TF无关。
BO-MBC患者与非BO-MBC患者检测到ctDNA的可能性相同；TF在BO-MBC患者中仍具有预后价值，TF＜1%与显著更好的预后相关。
