Tumor Tissue- versus Plasma-based Genotyping for Selection of Matched Therapy and Impact on Clinical Outcomes in Patients with Metastatic Breast Cancer

Abstract

PURPOSE: Actionable mutations can guide genotype-directed matched therapy. We evaluated the utility of tissue-based and plasma-based genotyping for the identification of actionable mutations and selection of matched therapy in patients with metastatic breast cancer (MBC). METHODS: Patients with MBC who underwent tissue genotyping (institutional platform, 91 gene assay) or plasma based cell-free DNA (cfDNA, Guardant360^®, 73 gene assay) between January 2016 and December 2017 were included. A chart review of records to identify subtype, demographics, treatment, outcomes, and tissue genotyping or cfDNA results was performed. The incidence of actionable mutationsand the selection of matched therapy in tissue genotyping or cfDNA cohorts was determined. The impact of matched therapy status on overall survival (OS) in tissue genotyping or cfDNA subgroups was determined with Cox regression analysis. RESULTS: Of 252 patients who underwent cfDNA testing, 232 (92%) had detectable mutations, 196 (78%) had actionable mutations, and 86 (34%) received matched therapy. Of 118 patients who underwent tissue genotyping, 90 (76%) had detectable mutations, 59 (50%) had actionable mutations, and 13 (11%) received matched therapy. For cfDNA patients with actionable mutations, matched versus non-matched therapy was associated with better OS (HR 0.41, 95% CI: 0.23-0.73, p=0.002), and this remained significant in a multivariable analysis correcting for age, subtype, visceral metastases, and brain metastases (HR = 0.46, 95% CI: 0.26-0.83, p = 0.010). CONCLUSION: Plasma-based genotyping identified high rates of actionable mutations, which was associated with significant application of matched therapy and better OS in patients with MBC.