Journal Article

Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA

White, Jason B., Addanki, Sridevi, Roy, Dhruvajyoti, Moulder, Stacy L., Lucci, Anthony, Barcenas, Carlos H., Sethi, Himanshu, Yam, Clinton, Meas, Salyna, Chen, Jennifer H., Rauch, Gaiane M., Kuerer, Henry M., Tripathy, Debu, Spickard, Erik, Liu, Minetta C., Korkut, Anil, Kalashnikova, Ekaterina, Sarli, Vanessa N., Bassett, Roland, Arun, Banu K., Rodriguez, Angel A.

2024

Overview

Background Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). Methods Patients with TNBC were enrolled between 2017–2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera TM , Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher’s exact tests were used for comparisons between groups and Kaplan–Meier analysis used for survival outcomes. Results In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response ( p  = 0.02), whereas CTC clearance was not ( p  = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS ( p  = 0.0002 and p  = 0.0034, respectively). Conclusions Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvant treatment / Adult / Aged / Analysis / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Automation / Biomarkers / Biomarkers, Tumor - blood / Biomedical and Life Sciences / Biomedicine / Biopsy / Blood / Breast cancer / Cancer / Cancer Research / Cancer therapies / Chemotherapy / Circulating Tumor DNA - blood / Circulating Tumor DNA - genetics / Clinical trials / CTC / ctDNA / Development and progression / DNA / Enumeration / Female / Genetic aspects / Health Promotion and Disease Prevention / Humans / Liquid biopsy / Liquid biopsy in neoadjuvant setting / Lymphatic system / Medical examination / Medical prognosis / Medicine/Public Health / Metastasis / Middle Aged / Neoadjuvant therapy / Neoadjuvant Therapy - methods / Neoplastic Cells, Circulating - metabolism / Neoplastic Cells, Circulating - pathology / Oncology / Patient outcomes / Patients / Plasma / Prognosis / Quality control / Standard of care / Surgery / Surgical Oncology / Treatment Outcome / Triple negative breast cancer / Triple Negative Breast Neoplasms - blood / Triple Negative Breast Neoplasms - drug therapy / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - mortality / Triple Negative Breast Neoplasms - pathology / Tumor markers / Tumors