A study led by Weill Cornell Medicine and NewYork-Presbyterian researchers has found that mysterious circulating tumor cells called double-positive (DP) cells are associated with shorter survival times in patients with advanced breast cancer. This finding highlights the potential importance of these poorly studied cells in breast cancer progression.
Circulating tumor cells are shed tumor cells that can give rise to secondary tumors (metastasis) and are commonly found in the blood of cancer patients. Dual-positive cells are circulating cells that carry markers of both tumor and immune cells and are thought to be hybrid cells resulting from rare fusions of tumor and immune cells. Recent studies have linked the presence of DP cells in a patient’s blood to worse outcomes in melanoma and pancreatic cancer.
In a new study published March 11 in the journal Science Translational Medicine, researchers found that DP cells are associated with shorter survival times in patients with advanced breast cancer, particularly in the aggressive “triple-negative” breast cancer subtype. The research team also showed in animal models that DP cells can seed breast cancer metastases.
A better understanding of the role of these abnormal cells in triple-negative breast cancer may help devise better treatments and ways to predict and monitor treatment response. ”
Dr. Carolina Reduzzi, co-lead author of the study and research assistant professor of cancer biology at Weill Cornell Medical School
Dr. Eleonora Nicolo, a cancer research instructor at Weill Cornell Medicine, is the study’s other co-lead author. Doctors. Reduzzi and Nicolò are members of the lab’s senior author Dr. Massimo Cristofanilli, a professor in the Department of Hematology and Medical Oncology at Weill Cornell Medical College and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The researchers initially analyzed blood samples from 340 women with advanced breast cancer who agreed to participate when the study began at Northwestern University, Dr. Cristofanilli’s hometown. DP cells tended to be fewer in number than normal circulating tumor cells, which are known risk factors for metastasis and shortened survival. However, the researchers identified at least one DP cell in 152 (44.7%) women. Median survival for patients with three or more detected DP cells was only 23.5 months, compared to 33.6 months for patients with fewer than three detected DP cells. The association between more than three DP cells and shorter median survival was tested in an additional group of 51 patients with advanced breast cancer who agreed to participate in the study at Dr. Cristofanilli’s clinic at NewYork-Presbyterian/Weill Cornell Medical Center.
A comparison of different breast cancer subtypes showed that the risk of shortened survival with DP cells was mainly concentrated in triple-negative breast cancer patients. This is a subtype in which tumor cells lack the three most common breast cancer markers: estrogen, progesterone, and HER2 receptors.
Supporting the hypothesis that DP cells originate from the fusion of tumor cells and macrophages, the researchers found that 60% of the patient-derived DP cells analyzed had standard macrophage markers. Additionally, the research team was only able to detect DP cells in the breast cancer mouse model when the mice had a normal immune system.
Approximately 29% of patients’ DP cells have genetic abnormalities called copy number alterations, which are commonly found in tumors. Although normal circulating tumor cells in patients are more likely to exhibit such abnormalities, DP cells appear to be fully capable of disseminating metastases in animal models.
This finding highlighted the relevance of DP cells in breast cancer and the importance of further studying DP cells. The research team is currently conducting a comprehensive characterization of the gene expression patterns of DP cells, which should provide a clearer picture of the cells’ origin.
“While our current treatments target regular cancer cells, DP cells have a different biology,” said Dr. Cristofanilli, scientific director and head of the liquid biopsy platform at the Englander Institute for Precision Medicine and associate director of precision oncology at the Sandra Edward Meyer Cancer Center. “We need to understand that better in order to effectively target them.”
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Reference magazines:
Reduzzi, C. others. (2026) Double-positive CTCs in advanced breast cancer patients indicate metastatic potential and prognostic value.. scientific translational medicine. DOI: 10.1126/scitranslmed.adw7698. https://www.science.org/doi/10.1126/scitranslmed.adw7698
