The circulating tumor DNA (ctDNA) alteration level predicts therapeutic response in metastatic breast cancer: Novel prognostic indexes based on ctDNA

• Authors: Binliang Liu, Central South University; Zheyu Hu, Central South University; Jialu Ran, Emory University; Ning Xie, Central South University; Can Tian, Central South University; Yu Tang, Central South University; Quchang Ouyang, Central South University
• Journal Title: BREAST
• Volume: Volume 65
• Publisher: CHURCHILL LIVINGSTONE | 2022-08-02, Pages 116-123
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.breast.2022.07.010
• Subjects: Health Sciences, Oncology; Biology, Biostatistics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Obstetrics & Gynecology; Breast cancer; Circulating tumor DNA; Genetic alterations; Progression -free survival (PFS); RESISTANCE; PLASMA

Abstract

Purpose: Circulating tumor DNA (ctDNA) has good clinical guiding value for metastatic breast cancer (MBC) patients. This study aimed to apply a novel genetic analysis approach for therapeutic prediction based on ctDNA alterations. Method: This nonrandomized, multicenter study recruited 223 MBC patients (NCT05079074). Plasma samples were collected for target-capture deep sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when progressive disease (PD) was evaluated. Samples were categorized into four levels according to the number of ctDNA alterations: level 1 (no alterations), level 2 (1–2 alterations), level 3 (3–4 alterations) and level 4 (≥5 alterations). According to ctDNA alteration level and variant allele frequency (VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors (ctle-RECIST) was established to assess treatment response and predict progression-free survival (PFS). Results: The median PFS in level 1 (6.63 months) patients was significantly longer than that in level 2–4 patients (level 2: 5.70 months; level 3–4: 4.90 months, p < 0.05). After 2 cycles of treatment, based on ctle-RECIST, the median PFS of level-based disease control rate (lev-DCR) patients was significantly longer than that of level-based PD (lev-PD) patients [HR 2.42 (1.52–3.85), p < 0.001]. In addition, we found that ctDNA level assessment could be a good supplement to radiologic assessment. The median PFS in the dual-DCR group tended to be longer than that in the single-DCR group [HR 1.41 (0.93–2.13), p = 0.107]. Conclusion: The ctDNA alteration level and ctle-RECIST could be novel biomarkers of prognosis and could complement radiologic assessment in MBC.