Data from: Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease

Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell‐free circulating tumor DNA (ctDNA) contains tumor‐specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow‐up. Using an approach combining low‐coverage whole‐genome sequencing of primary tumors and quantification of tumor‐specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA‐based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long‐term disease‐free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.

转移性乳腺癌（Metastatic breast cancer）通常在出现症状后才得以确诊，此时几乎已无治愈可能。无细胞循环肿瘤DNA（cell-free circulating tumor DNA，ctDNA）携带有肿瘤特异性染色体重排，可通过血浆样本进行检测分析。我们针对20例确诊原发性乳腺癌且接受长期随访的患者开展回顾性研究，评估ctDNA连续监测用于更早发现肿瘤转移的效果。本研究采用结合原发性肿瘤低覆盖度全基因组测序（low-coverage whole-genome sequencing）以及通过液滴数字PCR（droplet digital PCR）定量血浆中肿瘤特异性重排的分析方法，首次证实ctDNA监测在术后区分最终发生临床确诊复发的患者与未复发者时具有极高准确性：前者检出率达93%，后者为100%。在最终发生临床确诊转移的患者中，86%的病例通过ctDNA检测提前发现了异常，平均提前时长为11个月（范围0~37个月）；而长期无病生存期（disease-free survival）患者术后未检测到ctDNA。ctDNA载量可预测不良生存结局。本研究结果为早期乳腺癌开展更大规模验证研究奠定了理论基础，以评估ctDNA作为监测工具用于早期转移检测、治疗方案调整，并助力避免过度治疗的可行性。