Cell-free DNA Comparative Analysis of Genomic Landscape of First-line Hormone-receptor Positive Metastatic Breast Cancer From US and China

Abstract

Background: The differential mutation landscape between ethnics is more comparable when using the identical detecting platform.We explored the differences in genomic landscape of patients with hormone-receptor positive (HR+), HER2-negative MBC of first recurrence or Stage IV at diagnosis from the United States (US) and China (CN).Methods: Twenty-seven US patients and 65 CN patients had circulating tumor DNA (ctDNA) sequencing from plasma using the harmonized CLIA-certified, 152-gene PredicineCareTM liquid biopsy assay. Clinical outcomes were correlated with ctDNA variants. Progression-free survival (PFS) and overall survival analysis was performed for patients and compared using log-rank test. Results: Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The most common mutations detected included TP53, PIK3CA, CDH1, AKT1, ESR1, and BRCA2 in both US and CN patients. AKT1(18.5% vs. 3.1%, P = 0.008) and CDH1 mutations were more frequent in the US population (18.5% vs. 1.5%, P = 0.021), and gain of FGFR1 was more common in the CN cohort (7.4% vs. 24.6%, P = 0.048). PTEN deletion (5.7 months vs. 13.2 months, P = 0.03) and ESR1 alterations (9.0 months vs. 13.2 months, P = 0.02) were associated with significantly shorter PFS in CN cohort. Conclusions: To our knowledge, this is the first real world study using a single harmonized ctDNA assay to profile plasma samples of patients from the US and CN. Differential prevalence of the mutations with therapeutic potential were found between US and CN.