Abstract P3-01-14: Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort

Abstract

Abstract Background: There is unmet need for biomarkers to guide the treatment selection in MBC. We described phenotypic CTC heterogeneity in metastatic castrate resistant prostate cancer(mCRPC), and showed that pts with CTC high heterogeneity have improved OS with chemotherapy, while with pts low CTC heterogeneity pts have longer OS with AR inhibitors (Scher et al. 2017 Cancer Research). Here, the same methodology was applied to evaluate the feasibility of CTC heterogeneity analysis in MBC pts. Material and methods: 92 blood samples from MBC pts were processed for HER2 CTC analysis utilizing the Epic Sciences platform. Following enumeration, multi-dimensional phenotypic characterization analysis was performed utilizing protein expression and digital pathology features. 20 features from each CTC were clustered using unsupervised approach (K-means) and the optimal number of clusters was determined using the elbow method with greater than 85% of variance taken into account. Shannon Index was used to score intra-patient CTC heterogeneity. Results: CTCs were detected in 77.2% (71/92) of the MBC pts. 1501 CTCs from 60 pts were clustered into phenotypic subtypes which are distinctively different in nuclear size, circularity, CK and HER2 intensity etc. HER2 expression was enriched in cell types that had higher CK intensity and was more circular morphologies often associated with replicative stress. A wide range of CTC phenotypic heterogeneity was observed across pts, Shannon Index scores from 0 (low heterogeneity) to 1.67 (high heterogeneity) with a median of 0.60. CTC heterogeneity was independent of CTC counts, some low count pts had heterogeneous CTC subtypes while some high count pts had homogeneous CTC subtypes. Conclusions: Diverse inter- and intra-patient phenotypic CTC heterogeneity were observed in this MBC cohort, consistent with that seen in mCRPC and other MBC cohorts (Beverly H et al, ASCO 2018). Studies linking degree and patterns of CTC heterogeneity to therapeutic outcomes are ongoing. Citation Format: Wang Y, Hom B, Ontiveros P, Landaverde C, Roth E, Levin MK, Hippely S, Landers M, Dittamore R, O'Shaughnessy JA. Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort [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 P3-01-14.