Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer

• Published in: Breast cancer research and treatment Vol. 209; no. 3; pp. 493 - 502
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2025; Springer Nature B.V
• Subjects: Adult; Aged; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Chemotherapy; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Cohort analysis; Deoxyribonucleic acid; DNA; Female; High-Throughput Nucleotide Sequencing; Humans; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm, Residual; Next-generation sequencing; Oncology; Patients; Prognosis; Treatment Outcome; Tumors; Minimal residual disease; Liquid biopsy; Relapse; Breast cancer; CtDNA
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-024-07508-2

Purpose 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. Methods 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. Results 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. Conclusion 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.