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Liquid Biopsy Clinical Application Demonstrated for Metastatic Breast Cancer

By LabMedica International staff writers
Posted on 10 May 2016
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Image: The ANGLE Parsortix cell separation system (Photo courtesy of ANGLE).
Image: The ANGLE Parsortix cell separation system (Photo courtesy of ANGLE).
Metastasis is responsible for the vast majority of breast cancer related deaths and initial treatment recommendations for breast cancer are based on primary tumor biology from the initial solid biopsy at patient presentation.

Access to the secondary cancer site to obtain this tissue biopsy is challenging and requires the patient to undergo an invasive procedure, which causes trauma and delays treatment until they have recovered from the procedure. Furthermore the surgical intervention takes time to arrange, is expensive and diverts resources from care for the patient.

Scientists at the Norris Comprehensive Cancer Center (Los Angeles, CA, USA) enrolled metastatic breast cancer patients to a prospective, observational clinical study in which circulating tumor cells (CTCs) are enumerated and captured from 10-20 mL peripheral blood. CTCs, peripheral blood (PB), and metastatic sites were profiled with whole transcriptome shotgun sequencing. The team obtained fresh frozen tissue biopsies from the following metastatic sites: skin, brain, pleural effusion, pericardial effusion, breast, cerebrospinal fluid and bone tissue.

The CTC enumeration was performed via the Parsortix system (ANGLE plc, Guildford, UK) and metastatic sites were profiled with RNA Seq, the primary predictor via the HiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA). Bioinformatics analysis was then performed. NanoString PAM50 (NanoString Technologies, Seattle, WA, USA) and real-time polymerase chain reaction will be used as validation studies. For every one of the patients, CTCs were successfully harvested and RNA-Seq analysis successfully completed. This analysis demonstrated a statistically significant correlation between the expression signature of 192 genes in the Parsortix harvested CTCs with similar analysis of tissue obtained from an invasive biopsy of a secondary cancer site.

The study also suggests that the Parsortix system also has the potential to be a useful tool for identifying drug targets in metastatic breast cancer and might be utilized to assess the effectiveness of drugs under development in clinical trials. Replacement of the metastatic biopsy for breast cancer with a Parsortix blood test would be non-invasive, cheaper and faster, and could be repeated more frequently, thereby providing "real-time" information for therapy selection reflecting disease progression.

Julie E. Lang, MD, FACS, Director of the USC Breast Cancer Program, said, “As a breast cancer surgeon, I am very enthusiastic about the potential of liquid biopsy to gain information to guide the treatment of breast cancer patients based on the specific tumor biology for each patient. Our pilot data shows that potentially the same information can be obtained from a simple blood test using Parsortix as from an invasive tissue biopsy and indeed may be advantageous over invasive tissue biopsies in regards to the diverse sites of metastatic disease, thus providing a compelling rationale for use in clinical practice after further validation.” The study was presented at the American Association for Cancer Research Annual Meeting, held April 16-20, 2016, in New Orleans (LA, USA).

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