Triple-negative breast cancer (TNBC) is one of the most aggressive and difficult-to-treat forms of breast cancer.
Unlike other types, TNBC doesn’t respond to common hormonal or HER2-targeted therapies, making early and accurate diagnosis critical for improving outcomes.
Now, a team of researchers has developed a promising new molecular imaging technique that can detect multiple subtypes of TNBC, potentially transforming how this challenging disease is diagnosed and managed.
The study, published in The Journal of Nuclear Medicine, introduces a new imaging method that targets a specific protein in the tumor environment called extra domain A of fibronectin (EDA-FN).
This protein is commonly found in breast tumors, especially TNBC, and remains stable across different subtypes. That consistency makes it an ideal target for imaging in a disease known for its wide biological variability.
TNBC is not a single disease but a group of subtypes with different behaviors and treatment responses. Because of this, traditional imaging techniques often struggle to identify all forms of the disease, and the development of effective diagnostic tools has lagged behind those for other types of breast cancer.
To address this, researchers developed a PET (positron emission tomography) tracer based on a monoclonal antibody. The tracer, called [89Zr]Zr-DFO-F8, is designed to bind specifically to EDA-FN.
In lab tests and animal models, the tracer was able to locate and bind to TNBC tumors with high accuracy. It not only detected the tumors but also highlighted more aggressive forms of the disease, correlating closely with the levels of EDA-FN in the tumors.
Dr. Jason Lewis, lead researcher and Chair at Memorial Sloan Kettering Cancer Center, explained the significance of the findings: “We developed this imaging agent to overcome the problem of TNBC’s tumor cell diversity.
By targeting the stable EDA-FN protein in the tumor’s surrounding environment, rather than the tumor cells themselves, we were able to detect a range of TNBC subtypes with a single tool.”
In animal studies, the tracer successfully identified both subcutaneous and orthotopic (breast tissue-based) TNBC tumors. Its uptake in tumors matched the amount of EDA-FN present, showing its ability to accurately reflect disease severity.
The study opens up the possibility of using tumor microenvironment-based imaging, rather than relying only on tumor cell markers. This is important because many cancers, especially aggressive ones like TNBC, often change or lose the markers that most imaging tools rely on.
Targeting stable proteins like EDA-FN could create more reliable methods for diagnosing not only TNBC but other hard-to-image cancers as well.
Dr. Lewis believes this approach could expand the use of precision imaging, allowing doctors to better plan treatment and monitor how well a therapy is working. It could also help in selecting patients for clinical trials or identifying those who may benefit from newer, targeted therapies.
While the study was conducted in preclinical models, the results are promising and pave the way for future clinical trials in humans. If proven successful in patients, this imaging technique could become a valuable addition to the tools used to fight one of the most stubborn forms of breast cancer.
In summary, this new imaging method offers hope for earlier, more accurate diagnosis of triple-negative breast cancer. By targeting a stable and widely expressed protein in the tumor environment, the technique could overcome the limitations of current approaches and help guide better treatment decisions for patients facing this aggressive disease.
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The research findings can be found in Journal of Nuclear Medicine.
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