Liquid Biopsy Profiling with Multiple Tests in Patients with Metastatic Breast Cancer

Author:

Higa Nikki12ORCID,Welter Lisa13ORCID,Xu Liya145ORCID,Kolatkar Anand1,Bramlett Kelli S.6,Gjoerup Ole V.7,Graf Ryon7,Huang Richard S.P.7,Leary Rebecca J.8,Lee Young9,Perkins Jeremy G.1011,Riker Adam I.912,Singh Angad P.8,Tafra Lorraine13,Tweed Carol K.914,Shriver Craig D.1011ORCID,Hicks James13ORCID,Kuhn Peter1315161718ORCID

Affiliation:

1. Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA

2. Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

3. Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA

4. The Vision Center at Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA

5. USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

6. Thermo Fisher Scientific, Austin, TX 78744, USA

7. Foundation Medicine, Inc., Cambridge, MA 02141, USA

8. Novartis Biomedical Research, Cambridge, MA 02139, USA

9. Luminis Health, Anne Arundel Medical Center, DeCesaris Cancer Institute, Annapolis, MD 21401, USA

10. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA

11. Walter Reed National Military Medical Center, Bethesda, MD 20889, USA

12. Precision Healthcare Specialists, Naples, FL 34102, USA

13. Breast Care Architects, LLC., Crownsville, MD 21032, USA

14. Maryland Oncology Hematology, Annapolis, MD 21401, USA

15. Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

16. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

17. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA

18. Department of Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA

Abstract

The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.

Funder

Breast Cancer Research Foundation

National Cancer Institute’s Norris Comprehensive Cancer Center

Henry M. Jackson Foundation (HJF) for the Advancement of Military Medicine

HJF Cooperative Agreement with a Uniformed Services University of the Health Sciences (USUHS) Award: Breast Cancer Center of Excellence

Alan Joseph Endowed Fellowship

Vassiliadis Research Fund

Publisher

MDPI AG

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