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Personalized Detection of ctDNA Antedates Breast Cancer

By LabMedica International staff writers
Posted on 01 May 2019
Breast cancer is one of the most commonly diagnosed cancers worldwide and the second leading cause of cancer-related deaths in women. More...
The current standard of care for women with primary (non-metastatic) breast cancer is surgery, often followed with adjuvant therapy to eliminate microscopic minimal residual disease (MRD).

Circulating tumor DNA (ctDNA) detectable in blood plasma has been shown to reflect the mutational signatures of the primary tumor and is emerging as a potential non-invasive biomarker for monitoring tumor progression across different cancer types. However, up to 43% of breast cancer patients do not have hotspot mutations and thus cannot be monitored using a driver gene approach.

A large team of scientists collaborating with the Imperial College London (London, UK) recruited 49 primary breast cancer patients following surgery and adjuvant therapy. The scientists collected 208 plasma samples every six months for up to four years. Personalized assays targeting 16 variants selected from primary tumor whole exome data were tested in serial plasma for the presence of ctDNA by Signatera ultra-deep sequencing (Natera, San Carlos, CA, USA). Patient-specific somatic variants were identified by comparison of paired primary tumor and matched white blood cell DNA whole exome sequencing (WES) profiles for all 49 patients.

The investigators detected plasma ctDNA ahead of clinical or radiological relapse in 16 of the 18 relapsed patients (sensitivity of 89%); metastatic relapse was predicted with a lead time of up to two years (median=8.9 months; range: 0.5-24.0 months). None of the 31 non-relapsing patients were ctDNA-positive at any time point across 156 plasma samples (specificity of 100%). Of the two relapsed patients who were not detected in the study, the first had only a local recurrence, while the second patient had bone recurrence and had completed chemotherapy just 13 days prior to blood sampling.

The authors concluded that they had demonstrated that patient-specific ctDNA analysis can be a sensitive and specific approach for disease surveillance for breast cancer patients. More importantly, earlier detection of up to two years provides a possible window for therapeutic intervention. The study was published on April 16, 2019, in the journal Clinical Cancer Research.

Related Links:
Imperial College London
Natera


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