Dual-Positive Cells Linked to Worse Survival in Breast Cancer

An often-overlooked type of circulating tumor cell, dubbed “dual-positive” or DP cells, appears to be linked to poorer outcomes for women with advanced breast cancer, particularly those with the aggressive triple-negative subtype. The findings, published today in Science Translational Medicine, underscore the complexity of cancer progression and suggest that current diagnostic and treatment strategies may not be capturing the full picture of the disease.

What are Dual-Positive Cells?

Circulating tumor cells (CTCs) are cancer cells that have broken away from the primary tumor and are traveling through the bloodstream. They are considered a key driver of metastasis – the spread of cancer to other parts of the body. Traditionally, CTCs are identified by the presence of specific proteins on their surface, known as epithelial markers. However, DP cells are unusual because they express both epithelial markers, characteristic of tumor cells and leukocyte markers, typically found on immune cells. This suggests they may be hybrid cells formed through a rare fusion of tumor cells and immune cells, potentially including macrophages. Researchers at Weill Cornell Medicine and NewYork-Presbyterian led the study that revealed this connection.

“These cells are enigmatic,” explains Dr. Carolina Reduzzi, assistant professor of cancer biology research in medicine at Weill Cornell Medicine. “They don’t fit neatly into our existing understanding of how cancer spreads.” The presence of both tumor and immune cell markers on DP cells suggests a potentially unique mechanism of immune evasion, and metastasis.

Study Details and Findings

The research team analyzed blood samples from 340 women with advanced breast cancer. They found that patients with a higher proportion of DP cells in their blood had significantly shorter survival times. This association was particularly strong in women with triple-negative breast cancer, a particularly aggressive form of the disease that lacks the hormone receptors typically targeted by hormone therapies. The study, published March 11, 2026, also included animal models demonstrating that DP cells can indeed seed the development of breast cancer metastases.

Previous research had hinted at the importance of DP cells in other cancers, including melanoma and pancreatic cancer, where their presence also correlated with worse clinical outcomes. This recent study strengthens the evidence that DP cells are not simply a rare curiosity, but a potentially significant factor in cancer progression across different tumor types.

What Does This Mean for Patients?

It’s critical to emphasize that this research does not mean that all patients with advanced breast cancer should be immediately tested for DP cells. The study is a crucial first step in understanding the role of these cells, but further research is needed to determine how best to use this information in clinical practice. Currently, DP cell analysis is not a standard part of breast cancer diagnosis or treatment planning.

The findings do, however, highlight the need for more comprehensive monitoring of circulating tumor cells. Traditional CTC detection methods may be missing these DP cells, potentially underestimating the extent of the disease and the risk of metastasis. Developing more sensitive and accurate methods for detecting DP cells could lead to earlier diagnosis, more personalized treatment strategies, and improved outcomes for patients with advanced breast cancer.

Limitations and Areas for Further Research

The study, even as significant, has limitations. The researchers acknowledge that the exact mechanism by which DP cells form and contribute to cancer progression remains unclear. It is still unknown whether DP cells directly cause shorter survival, or if they are simply a marker of more aggressive disease. Further research is needed to investigate the molecular characteristics of DP cells, how they interact with the immune system, and how they respond to different therapies.

The study population was also limited to women with advanced breast cancer. It is unclear whether the findings would apply to women with earlier stages of the disease. The study did not investigate whether targeting DP cells directly could improve treatment outcomes. Future research should explore the potential of developing therapies specifically designed to eliminate these cells.

The Role of the Immune System

The fact that DP cells express both tumor and immune cell markers suggests a complex interplay between cancer cells and the immune system. These hybrid cells are able to evade immune surveillance, allowing them to survive and spread more effectively. Alternatively, they may actively suppress the immune response, creating a more favorable environment for tumor growth.

Understanding the role of the immune system in the formation and function of DP cells is crucial for developing new treatment strategies. Immunotherapies, which aim to boost the body’s own immune defenses against cancer, may be particularly effective in targeting these cells. However, more research is needed to determine how best to combine immunotherapies with other treatments to maximize their effectiveness.

What Comes Next: Ongoing Investigations and Clinical Trials

Researchers are now focused on several key areas. One priority is to refine methods for isolating and characterizing DP cells, making them easier to study. This includes developing more sensitive assays and improving our understanding of the specific markers expressed by these cells. Another focus is to investigate the molecular mechanisms driving DP cell formation – what triggers the fusion of tumor and immune cells? Ongoing studies are also exploring whether the presence of DP cells can be used as a biomarker to predict response to treatment, potentially guiding treatment decisions.

While no clinical trials are currently underway specifically targeting DP cells, the findings from this study are likely to spur the development of such trials in the future. These trials could evaluate the effectiveness of new therapies designed to eliminate DP cells or to prevent their formation. The National Cancer Institute maintains a comprehensive database of clinical trials, which patients can search to find potential opportunities: https://www.cancer.gov/about-cancer/treatment/clinical-trials.