New Study Links Dual-Positive Cells to Shorter Survival in Advanced Breast Cancer
A study conducted by investigators at Weill Cornell Medicine and NewYork-Presbyterian has established a link between dual-positive (DP) circulating tumor cells and shorter survival times in patients with advanced breast cancer. These cells, which exhibit markers for both tumor and immune cells, were particularly associated with reduced survival in the triple-negative breast cancer subtype and demonstrated the ability to contribute to metastasis in animal models.
Understanding Dual-Positive Cells
Circulating tumor cells (CTCs) are tumor cells that detach from a primary tumor and travel through the bloodstream, potentially forming secondary tumors, known as metastases. DP cells are a distinct type of circulating cell that possesses markers characteristic of both tumor cells and both tumor and immune cells. Researchers hypothesize that DP cells may be hybrid cells resulting from the fusion of tumor cells with immune cells. Previous research has indicated a connection between the presence of DP cells and worse outcomes in melanoma and pancreatic cancer.
Key Research Findings
The recent study, published in Science Translational Medicine on March 11, specifically connected the presence of DP cells to reduced survival in patients with advanced breast cancer. The association was particularly noted in patients with triple-negative breast cancer, a subtype characterized by the absence of estrogen, progesterone, and HER2 receptors on tumor cells. Animal models utilized in the study demonstrated that DP cells are capable of seeding breast cancer metastases. The study's co-first authors included Dr. Eleonora Nicolò and Dr. Carolina Reduzzi, with Dr. Massimo Cristofanilli serving as the senior author.
The research involved the analysis of blood samples from 340 women diagnosed with advanced breast cancer. While DP cells were less numerous compared to standard circulating tumor cells, at least one DP cell was detected in 152 (44.7%) of the participants.
Key findings regarding patient survival included:
Patients with three or more detected DP cells had a median survival time of 23.5 months.
In contrast, patients with fewer than three detected DP cells had a median survival time of 33.6 months.
This association was further validated in an additional group of 51 patients. The risk of shorter survival linked to DP cells was primarily observed in patients with triple-negative breast cancer.
Insights into DP Cell Biology
The study provided evidence supporting the hypothesis that DP cells originate from tumor-cell/macrophage fusions:
- 60% of patient-derived DP cells analyzed displayed a standard macrophage marker.
- DP cells were detectable in breast cancer mouse models only when the mice possessed intact immune systems.
Approximately 29% of patient DP cells exhibited genetic abnormalities known as copy number alterations, which are common in tumors. Although ordinary circulating tumor cells more frequently showed such abnormalities, DP cells in animal models demonstrated the ability to form metastases.
Future Implications
The findings underscore the relevance of DP cells in breast cancer progression. Ongoing research aims to characterize the gene expression patterns of DP cells to better define their cellular origins. A more comprehensive understanding of the distinct biology of DP cells is considered crucial for developing targeted therapies and monitoring strategies, as existing treatments predominantly focus on ordinary cancer cells.