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

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). Experimental Design: 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 cfDN A results was performed. The incidence of actionable mutations and 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 cIDN A 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 nonmatched therapy was associated with better OS [HR 0.41, 95% confidence interval (CI): 0.23-0.73, P =0.002], and this remained significant in a multivatiable analysis correcting for age, subtype, visceral metastases, and brain metastases (HR = 0.46, 95% CI: 0.26-0.83, p = 0.010). Conclusions: 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.

Automated summary

Plasma-based genotyping can identify high rates of actionable mutations, leading to significant application of matched therapy and improved overall survival in patients with metastatic breast cancer.