Garcia-Murillas Isaac, Cutts Rosalind J, Walsh-Crestani Giselle, Phillips Edward, Hrebien Sarah, Dunne Kathryn, Sidhu Kally, Daber Robert, Hubert Benjamin, Graybill Chiharu, DeFord Peter M, Wooten David J, Zhao Jianhua, Ellsworth Rachel E, Johnston Stephen R D, Ring Alistair, Russell Simon, Evans Abigail, Skene Anthony, Wheatley Duncan, Smith Ian E, Korn W Michael, Turner Nicholas C
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Breast Unit, Royal Marsden Hospital, London, UK.
Breast Cancer Res Treat. 2025 Feb;209(3):493-502. doi: 10.1007/s10549-024-07508-2. Epub 2024 Oct 18.
Detection of molecular residual disease (MRD) allows for the identification of breast cancer patients at high-risk of recurrence, with the potential that early initiation of treatment at early stages of relapse could improve patient outcomes. The Invitae Personalized Cancer Monitoring™ assay (PCM) is a newly developed next-generation sequencing approach that utilizes up to 50 patient-specific, tumor-informed DNA variants, to detect circulating tumor DNA (ctDNA). The ability of the PCM assay to detect MRD before clinical relapse was evaluated.
The cohort included 61 female patients with high-risk breast cancer who underwent neoadjuvant chemotherapy. Plasma samples were collected before and during neoadjuvant therapy, after surgery and during monitoring. PCM was used to detect ctDNA at each time point.
The sensitivity to detect ctDNA in plasma from patients who relapsed during the monitoring phase was 76.9% (10/13). Specificity and positive predictive values were both 100% with all (10/61, 16%) of the patients who had ctDNA detected during the monitoring phase subsequently relapsing. Detection of ctDNA during monitoring was associated with a high-risk of future relapse (HR 37.2, 95% CI 10.5-131.9, p < 0.0001), with a median lead-time from ctDNA detection to clinical relapse of 11.7 months.
PCM detected ctDNA in patients who relapsed with a long lead-time over clinical relapse, shows strong association with relapse-free survival and may be used to identify patients at high-risk for relapse, allowing for earlier intervention.
检测分子残留病（MRD）有助于识别具有高复发风险的乳腺癌患者，早期复发阶段尽早开始治疗有可能改善患者预后。Invitae个性化癌症监测™检测法（PCM）是一种新开发的下一代测序方法，它利用多达50个患者特异性的、肿瘤信息性DNA变异来检测循环肿瘤DNA（ctDNA）。评估了PCM检测法在临床复发前检测MRD的能力。
该队列包括61例接受新辅助化疗的高危乳腺癌女性患者。在新辅助治疗前和治疗期间、手术后及监测期间采集血浆样本。在每个时间点使用PCM检测ctDNA。
监测阶段复发患者血浆中ctDNA的检测灵敏度为76.9%（10/13）。特异性和阳性预测值均为100%，监测阶段检测到ctDNA的所有患者（10/61，16%）随后均复发。监测期间ctDNA的检测与未来复发的高风险相关（HR 37.2，95%CI 10.5 - 131.9，p < 0.0001），从ctDNA检测到临床复发的中位提前期为11.7个月。
PCM在临床复发前很长时间就检测到复发患者的ctDNA，与无复发生存期有很强的相关性，可用于识别复发高危患者，从而实现更早的干预。
