ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease

• Published in: NPJ breast cancer Vol. 9; no. 1; p. 10
• Main Authors: Stecklein, Shane R, Kimler, Bruce F, Yoder, Rachel, Schwensen, Kelsey, Staley, Joshua M, Khan, Qamar J, O'Dea, Anne P, Nye, Lauren E, Elia, Manana, Heldstab, Jaimie, Home, Trisha, Hyter, Stephen, Isakova, Kamilla, Pathak, Harsh B, Godwin, Andrew K, Sharma, Priyanka
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 06.03.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Biomarkers; Breast cancer; Cancer therapies; Chemotherapy; Genetic testing; Immunotherapy; Medical prognosis; Mutation; Patients
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-023-00512-7

Triple-negative breast cancer (TNBC) patients with residual disease (RD) after neoadjuvant systemic therapy (NAST) are at high risk for recurrence. Biomarkers to risk-stratify patients with RD could help individualize adjuvant therapy and inform future adjuvant therapy trials. We aim to investigate the impact of circulating tumor DNA (ctDNA) status and residual cancer burden (RCB) class on outcomes in TNBC patients with RD. We analyze end-of-treatment ctDNA status in 80 TNBC patients with residual disease who are enrolled in a prospective multisite registry. Among 80 patients, 33% are ctDNA positive (ctDNA+) and RCB class distribution is RCB-I = 26%, RCB-II = 49%, RCB-III = 18% and 7% unknown. ctDNA status is associated with RCB status, with 14%, 31%, and 57% of patients within RCB-I, -II, and -III classes demonstrating ctDNA+ status (P = 0.028). ctDNA+ status is associated with inferior 3-year EFS (48% vs. 82%, P < 0.001) and OS (50% vs. 86%, P = 0.002). ctDNA+ status predicts inferior 3-year EFS among RCB-II patients (65% vs. 87%, P = 0.044) and shows a trend for inferior EFS among RCB-III patients (13% vs. 40%, P = 0.081). On multivariate analysis accounting for T stage and nodal status, RCB class and ctDNA status independently predict EFS (HR = 5.16, P = 0.016 for RCB class; HR = 3.71, P = 0.020 for ctDNA status). End-of-treatment ctDNA is detectable in one-third of TNBC patients with residual disease after NAST. ctDNA status and RCB are independently prognostic in this setting.