Abstract B141: Landscape of circulating tumor DNA (ctDNA) in refractory metastatic breast cancer: Real-time evaluation of treatment-resistance

Background: Liquid biopsy is among the most important technological innovations in oncology in the past few years with the ability to provide real-time prognostic and predictive information. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) contain genetic information released by the tumor of origin or metastasis in the bloodstream. Therefore, genetic alterations occurring in the tumor at the time of diagnoses or after treatment failure, can be detected with a simple blood sample. The efforts are now focused on demonstrating the clinical value of this assessment to improve treatment outcomes. Metastatic breast cancer (MBC) is a heterogeneous disease showing molecular evolution over time representing a challenge for selection of appropriate palliative treatment without longitudinal use of a sensitive diagnostic method. Methods: We retrospectively identified ctDNA data from a single institution (Northwestern University). All patients had next-generation sequencing performed by Guardant Health (Redwood City, CA) from 2015-2019 for clinical evaluation, and patients were consented for participation in a prospective registry study. Reports were evaluated for type of genomic alterations, number of alterations, and mutant allele frequency (MAF) of the dominant clone. Clinical information including demographics, pathology, imaging, treatment, and response data were collected via patient chart review. Associations were tested through Fisher’s exact test or Kruskal-Wallis test as statistically appropriate. Matched paired samples were investigated through McNemar test. Results: We evaluated a cohort of 255 patients with MBC. In total, 371 ctDNA reports were reviewed, including 116 patients with serial assessments. Baseline ctDNA evaluation occurred at a median of 3 lines of therapy (interquartile range (IQR): 1 – 5). Median number of detected alterations was 4 (IQR: 2-7), while median MAF was 4% (IQR: 0.6% - 17.9%). The most frequent mutations detected across the entire cohort, were PIK3CA and TP53, while MYC, FGFR1, PIK3CA, and ERBB2 were the most commonly detected amplifications. 40% of patients had PIK3CA aberrations observed in the analyzed plasma samples (28% amplification, 22% H1047R, 11% E542K), which was independent of breast cancer subtype. Particularly, interesting and with clinical relevance were the results from the hormone-receptor positive (HR+) breast cancer cohort. In this subset, 30% of patients had ESR1 mutations (27% D538G, 19% Y537S, 12% Y537N, 11% E380Q)which was associated with resistance to endocrine therapy. When examining the correlation with treatment lines, only ESR1 and FGFR1 were associated with collection beyond the first line of therapy for HR+ patients (P=0.003 and P Citation Format: ELENA VAGIA, Andrew Adam Davis, Lorenzo Gerratana, Ami Shah, Amir Behdad, William Gradishar, Firas Wehbe, Massimo Cristofanilli. Landscape of circulating tumor DNA (ctDNA) in refractory metastatic breast cancer: Real-time evaluation of treatment-resistance [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B141. doi:10.1158/1535-7163.TARG-19-B141