PURPOSE Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. EXPERIMENTAL DESIGN We profiled 93 genes in tissue from 193 patients with early breast cancer. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. RESULTS At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR = 0.062; 95% CI, 0.01-0.48; P = 0.0077). Of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were nonresponders (RCB II, n = 8; RCB III, n = 22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, whereas 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. CONCLUSIONS Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III.

中文翻译：

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乳腺癌患者新辅助治疗期间 ctDNA 的持续存在是肿瘤反应不佳的重要预测因素。


目的 新辅助全身治疗 (NST) 期间准确的反应评估提出了临床挑战。因此，基于无细胞循环肿瘤 DNA (ctDNA) 的肿瘤反应微创评估可能有益于指导治疗决策。实验设计 我们分析了 193 名早期乳腺癌患者组织中的 93 个基因。为 145 名患者设计了患者特异性检测，以追踪 NST 期间血浆中的 ctDNA。 ctDNA 的存在和水平与完全病理反应 (pCR) 和残留癌症负荷 (RCB) 以及肿瘤的临床病理特征相关，以确定 ctDNA 释放的潜在指标。结果 基线时，63/145 (43.4%) 患者可检测到 ctDNA，治疗中期 (MT) 25/63 (39.7%) 患者和治疗结束时 15/63 (23.8%) 患者持续存在 ctDNA。 MT 时的 ctDNA 检测与较高的 RCB 显着相关（OR = 0.062；95% CI，0.01-0.48；P = 0.0077）。在 MT 时可检测到 ctDNA 的 31 名患者中，30 名患者 (96.8%) 无反应（RCB II，n = 8；RCB III，n = 22），只有 1 名患者对治疗有反应（RCB I）。考虑到所有 145 名基线 (BL) 血浆患者，没有 RCB 0 患者和只有 6.7% 的 RCB I 患者在 MT 时检测到 ctDNA，而 RCB II/III 患者中分别有 30.6% 和 29.6% 的 ctDNA 检测到。 ctDNA 阳性结果。结论 总体而言，我们的结果表明，MT 时 ctDNA 的检测和持续存在可能会对新辅助治疗的反应产生负面预测，并识别出无法实现 pCR 或被分类为 RCB II/III 的患者。