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

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 ctDNA in metastatic breast cancer (mBC). The primary objective of this study is 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 (ie. 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.