Abstract P4-01-06: Comparison of Tumor Genotyping and Cell-Free Circulating Tumor DNA Sequencing in Metastatic Breast Cancer Patients and Their Utility in the Selection of Matched Therapy

Background: Oncogenic mutations are potential targets for therapeutic intervention in metastatic breast cancer (MBC). While tumor genotyping (TG) has been viewed as the gold standard for identifying oncogenic mutations, cell-free circulating tumor DNA (cfDNA) is emerging as an alternate technique. We previously reported the selection of matched therapy targeted to an actionable mutation based on either TG or cfDNA testing (Vidula N, ASCO, 2018). Therefore, we are now comparing TG and cfDNA results in MBC patients undergoing both tests to examine their relative utility in the selection of matched therapy. Methods: Patients with MBC at an academic institution who underwent both TG (Next Generation Sequencing/NGS, institutional platform, 104 gene assay) and cfDNA testing (NGS/Guardant360, 73 gene assay) between 1/2016-10/2017 were identified. A chart review was conducted to identify tumor subtype, demographics, treatment, TG and cfDNA results, and clinical outcomes. The relative utility of these tests in the selection of matched therapy was determined, and linked with clinical outcomes (progression-free survival and overall survival). Results: Thirty patients who underwent both TG and cfDNA testing were identified. The median age was 60 years, the majority (97%) had hormone receptor (HR) positive/HER2 negative disease, and most patients had recurrent disease (83.3%) at MBC diagnosis. The median number of therapies prior to obtaining either test was 1 (cfDNA range 0-9, TG range 0-8). The majority had simultaneous cfDNA and tumor genotyping testing (83.3%) versus sequential testing (16.7%). Twenty-four (80%) patients had actionable mutations detected by cfDNA compared to 19 (63.3%) patients with actionable mutations detected by TG. The median number of actionable mutations detected by cfDNA was 2 (range 0-11) compared with a median of 1 (range 0-4) detected by TG. Failure of TG occurred in 2 of 30 patients (6.7%) but no test failures were seen with cfDNA. Eleven of 30 patients (36.7%) had ≥ 1 concordant mutation via cfDNA and TG. Altogether, 12 out of 30 (40%) patients received matched therapy, 5 of which were based on cfDNA actionable mutations alone (ESR1, ERBB2, CCND1, and PIK3CA), and 7 based on cfDNA and TG results (ESR1, PIK3CA, STK11, and BRCA). Twelve of 24 (50%) patients with actionable cfDNA mutations went on to receive matched therapy compared with 7 of 19 (36.8%) patients with actionable TG results. Matched therapies included SERDs, inhibitors of CDK 4/6, PI3K, mTOR, HER2 directed therapy, and DNA damaging chemotherapy. The impact of matched therapy on survival outcomes will be presented at the meeting. Conclusions: In patients undergoing both TG and cfDNA testing, both tests identify a significant cohort of HR+ MBC patients with actionable mutations, with greater detection of actionable mutations by cfDNA. Greater application of matched therapy occurred via cfDNA, which independently informed the selection of matched therapies. Further research is needed to prospectively evaluate the clinical utility of blood based genotyping assays versus TG for patients with MBC. Citation Format: Vidula N, Juric D, Niemierko A, Spring L, Moy B, Malvarosa G, Yuen M, Habin K, Shin J, Peppercorn J, Isakoff S, Ellisen L, Iafrate AJ, Bardia A. Comparison of tumor genotyping and cell-free circulating tumor DNA sequencing in metastatic breast cancer patients and their utility in the selection of matched therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-06.