An enigmatic type of circulating tumour cell, called a dual-positive (DP) cell, is associated with shorter survival in patients with advanced breast cancer, according to a study led by investigators at Weill Cornell Medicine and New York-Presbyterian in the USA.
The findings highlight the potential importance of these understudied cells in breast cancer progression.
Circulating tumour cells are tumour cells that have broken away and can seed secondary tumours (metastases), and they are commonly detected in the blood of patients with cancer.
Dual-positive cells are circulating cells that bear both tumour-cell and immune-cell markers and are thought to be hybrid cells resulting from rare fusions of tumour cells with immune cells.
Featured Event
Recent studies have linked DP cells’ presence in patients’ blood to worse outcomes in melanoma and pancreatic cancer.
In the new study, published March 11 in Science Translational Medicine, the researchers linked DP cells to shorter survival times in patients with advanced breast cancer, especially the aggressive “triple-negative” breast cancer subtype. The team also showed, using animal models, that DP cells can seed breast cancer metastases.
“A better understanding of the role of these unusual cells in triple-negative breast cancer might help us devise better treatments and methods for predicting and monitoring treatment responses,” said study co-first author Dr. Carolina Reduzzi, assistant professor of cancer biology research in medicine at Weill Cornell Medicine.
Dr. Eleonora Nicolò, instructor of cancer research in medicine at Weill Cornell Medicine, is the other co-first author of the study.
The team initially analysed blood samples from 340 women with advanced breast cancer who had agreed to participate in the research study when it began at Northwestern University, where Dr. Cristofanilli was originally located.
DP cells tended to be less numerous than ordinary circulating tumour cells, which are a known risk factor for metastasis and shorter survival. However, the researchers identified at least one DP cell in 152 (44.7%) of the women.
Patients with three or more detected DPs had a median survival of just 23.5 months, compared with 33.6 months for patients with fewer than 3 detected DPs.
The association between more than 3 DP cells and shorter median survival was validated in an additional group of 51 patients with advanced breast cancer who agreed to participate in the study at Dr. Cristofanilli’s clinic at New York-Presbyterian/Weill Cornell Medical Centre.
Comparisons of different breast cancer subtypes indicated that the shorter-survival risk from DP cells was concentrated mainly among patients with triple-negative breast cancer, a subtype in which tumour cells lack the three most common breast tumour markers: oestrogen, progesterone, and HER2 receptors.
Supporting the hypothesis that DP cells originate from tumour-cell/macrophage fusions, the researchers found that 60% of the analysed DP cells from patients bore a standard macrophage marker.
Moreover, the team was able to detect DP cells in breast cancer mouse models only when the mice had intact immune systems.
About 29% of patient DP cells had genetic abnormalities called copy number alterations, which are commonly found in tumours.
Although patients’ circulating tumour cells were more likely to exhibit such abnormalities, DP cells appeared fully capable of seeding metastases in animal models.
The findings underscored the relevance of DP cells in breast cancer and the need to study them further.
The team is currently conducting a comprehensive characterisation of DP cells’ gene expression patterns, which should better define their cellular origins.
“Our current therapies target ordinary cancer cells, but DP cells have a different biology,” said Dr.Cristofanilli, who is also the scientific director and head of the Liquid Biopsy Platform at the Englander Institute for Precision Medicine and the associate director of precision oncology at the Sandra and Edward Meyer Cancer Centre. “We need to understand that better if we’re going to target them effectively.”
Source: Weill Cornell Medicine