Recent research from institutions in London and Australia has advanced the understanding and application of DNA analysis in breast cancer. One study focuses on a new DNA blood test designed to predict treatment response for advanced breast cancer patients, while another explores DNA barcoding to track cancer cell diversity in biopsies, aiming to improve diagnostic accuracy and reliability.
Predicting Treatment Response with Circulating Tumour DNA
Researchers at the Institute of Cancer Research (ICR) in London have developed a liquid biopsy designed to predict the effectiveness of breast cancer treatments. This test analyzes circulating tumour DNA (ctDNA) released by cancer cells into the bloodstream, with the aim of indicating a patient's likely response to specific treatments before they begin.
The test was trialled using blood samples from 167 patients with advanced breast cancer, collected before treatment and again four weeks into the first treatment cycle.
Key Findings:
- A strong association was observed between low ctDNA levels at the start of treatment and a positive treatment response. Similar associations were found with ctDNA levels measured after four weeks of treatment.
- For patients with specific mutations (ESR1, HER2, AKT1, AKT, or PTEN) receiving targeted treatments: Undetectable ctDNA levels after four weeks of treatment were associated with a longer progression-free survival of 10.6 months, compared to 3.5 months for those with detectable ctDNA.
- For patients with triple-negative breast cancer receiving a combination of olarparib and ceralasertib:
- Low pre-treatment ctDNA levels were associated with longer progression-free survival (10.2 months versus 4.4 months).
- The treatment response rate was 40% for patients with low ctDNA levels, compared to 9.7% for those with higher levels.
- After four weeks of treatment, patients with undetectable ctDNA maintained cancer control for 12 months, versus 4.3 months for those with detectable ctDNA.
Early prediction of treatment response could enable patients to avoid ineffective drugs and receive alternative therapies, potentially improving outcomes.
The potential application of these tests extends to early-stage breast cancers, which could facilitate faster, more personalized, and more effective treatment decisions.
Tracking Cancer Cell Diversity with DNA Barcoding
Australian scientists from the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI, and Peter MacCallum Cancer Centre have investigated the use of DNA barcoding to track cancer cells in both solid and liquid biopsies. The research aims to understand how these biopsy types capture the diverse cellular composition (heterogeneity) within tumors, which can vary in aggressiveness and treatment sensitivity.
The team optimized a DNA barcoding technique that uses lentiviruses to label individual cancer cells with unique DNA tags, functioning as barcodes. These barcodes allow researchers to track and identify cells in tumors and matched biopsies.
Key Findings:
- DNA barcodes shed by the primary tumor were detected in blood and plasma samples for the first time.
- Tumors in different models shed varying amounts of DNA into the bloodstream, even when their cancer cell composition appeared similar.
- The varying detectability of DNA tags across models suggests that DNA shedding is model-specific and could potentially lead to false-negative liquid biopsy results.
- Findings indicated that DNA shedding in the bloodstream varied based on factors such as necrosis, tumor burden, and preclinical models.
- Barcode diversity in the center of primary tumors was significantly higher than in the periphery, which could affect the interpretation of solid biopsies.
- While research suggests that both liquid and solid biopsies generally represent tumor composition, combining these strategies may offer a more accurate representation of the disease due to observed variability between tumors.
Liquid biopsies are recognized as a non-invasive method to monitor disease progression.
This research aims to contribute to understanding factors influencing DNA shedding from tumors, which could enhance the clinical utility of liquid biopsies for diagnosis and treatment strategies.