Next-Generation Sequencing of Patients With Breast Cancer in Community Oncology Clinics

Abstract

Molecular biomarkers informing disease diagnosis, prognosis, and treatment decisions in patients with breast cancer are being uncovered by next-generation sequencing (NGS) technologies. In this study, we survey how NGS is used for patients with breast cancer in real-world settings with a focus on physician behaviors and sequencing results. We conducted a retrospective analysis of patients with breast cancer who received NGS testing from commercial vendors as part of standard of care from 2014 to 2019. A total of 2,635 NGS reports from 2,316 unique breast cancer patients were assessed. Hormone receptor and human epidermal growth factor receptor 2 statuses were abstracted from patient medical records. Comparative gene amplification and mutation frequencies were analyzed using Pearson's correlation and Lin's concordance statistics. The number of physicians ordering NGS tests for patients with breast cancer increased more than six-fold from 2014 to 2019. Tissue- and plasma-based tests were ordered roughly equally by 2019, with plasma-based testing ordered most frequently in hormone receptor-positive subtypes. Patients with triple-negative breast cancer were most likely to receive NGS testing. Gene amplifications including ERBB2 were detected less frequently in our real-world data set as compared to previous genomic landscape studies, whereas the opposite was true for gene mutations including ESR1. Pathogenic mutations in the PI3K pathway (38.6%) and DNA damage repair pathway (11.0%) were frequently reported. Alterations were also reported across other cellular pathways. Overall, we found that an increasing number of physicians in community settings are adopting NGS in the care of patients with breast cancer. Discrepancies between our real-world NGS data and previous genomic landscape studies are likely owed to the prevalence of plasma-based testing in community oncology clinics, as the reference data were from tissue-based NGS alone.