TARGETING the gut–mast cell relationship could prevent breast cancer from spreading and recurring, enabling a personalised, customisable approach to treatment. According to researchers from the University of Virginia (UVA) Cancer Center, Charlottesville, USA, this finding could help doctors to develop ways to stop breast cancer from metastasising.
Blood cells that help to regulate the immune response to disease and allergens, mast cell behaviour, and function could be influenced by the gut microbiome in the presence of tumours. The gut microbiome can reprogramme mast cells, which can happen when the microbiome is disrupted.
Gut microbiome disruption usually occurs due to poor diet, obesity, long-term antibiotic use, and other factors. According to Melanie R. Rutkowski, UVA Cancer Center and the UVA School of Medicine (SoM), Charlottesville, USA, mast cells restructure “tissue architecture in such a way that tumour cells metastasise to other organs.” As 29% of females and 22% of males with metastatic breast cancer survive after 5 years, this finding could be vital in enabling doctors to predict which patients are at high-risk of cancer recurrence following treatment.
Using mice models, the researchers discovered that an unhealthy microbiome resulted in mast cells accumulating in breast tissue, which continued after tumour formation in hormone receptor-positive breast cancer. Furthermore, they also discovered an increased amount of collagen in the breast tissue of mice, which encouraged earlier cancer spread. However, blocking the process that led to mast cell accumulation reduced the tumour spread to the lungs.
Rutkowski noted: “We show gut commensal dysbiosis, an unhealthy and inflammatory gut microbiome, systemically changes the mammary tissues of mice that do not have cancer. The tissue changes enhance infiltration of mast cells that, in the presence of a tumour, facilitate breast tumour metastasis.”
Tissue samples from human patients with hormone receptor-positive breast cancer also had an increased number of mast cells and collagen deposits. The researchers noted a correlation between the number of mast cells and amount of collagen and the risk of recurring breast cancer. While Rutkowski acknowledges that there is controversy surrounding the role that mast cells play in breast cancer, this investigation implied that considering “mast cell functional attributes, tissue collagen density, and mast cell location” would help to better define the relationship between mast cells and metastasising breast tumours.