Genomic Landscape of Circulating-Tumor DNA in a Diverse Cohort of Metastatic Breast Cancer Patients

Abstract

Introduction: Breast cancer is the most prevalent cancer and the second leading cause of cancer death among women in the United States. Liquid biopsy is becoming a more commonly accepted method in clinical practice. Thus, there is a need to investigate ways to utilize circulating-tumor DNA (ctDNA) in metastatic breast cancer (mBC). The primary objective of this study was to characterize the genomic landscape of ctDNA in a diverse patient population and across different subtypes of mBC. Methods: We analyzed the ctDNA profile in patients (n = 45) with mBC who received a Guardant360 liquid biopsy test. Patient demographics, age at diagnosis, race, subtype, and mutations were included in the analysis. Results: The majority of patients (n = 39, 86.7%) had at least one gene alteration detected in their liquid biopsy. We found no statistically significant differences in genomic landscape according to race. However, there were differences seen in tumor genomics according to age and subtype. Postmenopausal patients were more likely to have detectable disease on liquid biopsy compared to premenopausal patients (p = 0.001). Mutations in ESR1 (n = 10) and PIK3CA (n = 8) were more commonly seen in hormone positive (HR+) mBC, where known tailored treatment options are available (i.e., fulvestrant and alpelisib respectively). The most common alterations detected include TP53 (n = 22) followed by PIK3CA (n = 15), ESR1 (n = 11), CCND1 (n = 7), and ERBB2 (n = 7). Conclusion: Liquid biopsies are effective tools that can reveal clinically relevant information including mutational status and therapeutic options.