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Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).

Publication ,  Journal Article
Magbanua, MJM; Rugo, HS; Wolf, DM; Hauranieh, L; Roy, R; Pendyala, P; Sosa, EV; Scott, JH; Lee, JS; Pitcher, B; Hyslop, T; Barry, WT ...
Published in: Clin Cancer Res
March 15, 2018

Purpose: We profiled circulating tumor cells (CTCs) to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC).Methods: CTCs were isolated from 105 patients with MBC using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACS), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n = 151) and genome-wide copy-number analysis by array comparative genomic hybridization (aCGH; n = 49).Results: Combined transcriptional and genomic profiling showed that CTCs were 26% ESR1-ERBB2-, 48% ESR1+ERBB2-, and 27% ERBB2+ Serial testing showed that ERBB2 status was more stable over time compared with ESR1 and proliferation (MKI67) status. While cell-to-cell heterogeneity was observed at the single-cell level, with increasingly stable expression in larger pools, patient-specific CTC expression "fingerprints" were also observed. CTC copy-number profiles clustered into three groups based on the extent of genomic aberrations and the presence of large chromosomal imbalances. Comparative analysis showed discordance in ESR1/ER (27%) and ERBB2/HER2 (23%) status between CTCs and matched primary tumors. CTCs in 65% of the patients were considered to have low proliferation potential. Patients who harbored CTCs with high proliferation (MKI67) status had significantly reduced progression-free survival (P = 0.0011) and overall survival (P = 0.0095) compared with patients with low proliferative CTCs.Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time. Clin Cancer Res; 24(6); 1486-99. ©2018 AACR.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2018

Volume

24

Issue

6

Start / End Page

1486 / 1499

Location

United States

Related Subject Headings

  • Single-Cell Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis
  • MCF-7 Cells
  • Kaplan-Meier Estimate
  • Humans
  • Genomics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Magbanua, M. J. M., Rugo, H. S., Wolf, D. M., Hauranieh, L., Roy, R., Pendyala, P., … Park, J. W. (2018). Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance). Clin Cancer Res, 24(6), 1486–1499. https://doi.org/10.1158/1078-0432.CCR-17-2312
Magbanua, Mark Jesus M., Hope S. Rugo, Denise M. Wolf, Louai Hauranieh, Ritu Roy, Praveen Pendyala, Eduardo V. Sosa, et al. “Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).Clin Cancer Res 24, no. 6 (March 15, 2018): 1486–99. https://doi.org/10.1158/1078-0432.CCR-17-2312.
Magbanua, Mark Jesus M., et al. “Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).Clin Cancer Res, vol. 24, no. 6, Mar. 2018, pp. 1486–99. Pubmed, doi:10.1158/1078-0432.CCR-17-2312.
Magbanua MJM, Rugo HS, Wolf DM, Hauranieh L, Roy R, Pendyala P, Sosa EV, Scott JH, Lee JS, Pitcher B, Hyslop T, Barry WT, Isakoff SJ, Dickler M, Van’t Veer L, Park JW. Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance). Clin Cancer Res. 2018 Mar 15;24(6):1486–1499.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2018

Volume

24

Issue

6

Start / End Page

1486 / 1499

Location

United States

Related Subject Headings

  • Single-Cell Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis
  • MCF-7 Cells
  • Kaplan-Meier Estimate
  • Humans
  • Genomics