The first direct evidence that respiratory viruses can trigger metastatic breast cancer has been published in Nature. Researchers from the University of Colorado Anschutz Medical Campus, Montefiore Einstein Comprehensive Cancer Center, and Utrecht University conducted the study using mice and patient data.
The research shows that breast cancer cells left dormant in the lungs after initial treatment may become active again following exposure to viruses like SARS-CoV-2 and influenza.
Dormant Cancer Cells Reactivated by Viral Infections in Mouse Models
The researchers demonstrated how breast cancer cells that had quietly settled in the lungs could be reawakened by viral infections using specialised mouse models. Within just days of exposure to SARS-CoV-2 or influenza, these dormant cells began multiplying rapidly, forming visible metastatic lesions in two weeks.
“Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames,” explained Dr James DeGregori, senior author and deputy director of the CU Cancer Center.
The key player behind this reactivation? Interleukin-6 (IL-6), a protein released during inflammation. According to the study, IL-6 was identified as a crucial trigger in the process that reawakens these “sleeper” cells.
“The identification of IL-6 as a key mediator in arousing DCCs from dormancy suggests that using IL-6 inhibitors or other targeted immunotherapies might prevent or lessen the resurgence of metastasis following viral infection,” said Dr Julio Aguirre-Ghiso, co-leader of the study.
Population-Level Evidence Supports Laboratory Findings
The researchers turned to human data from two major databases to assess whether this phenomenon translated beyond the lab. Their analysis of the UK Biobank, which includes over half a million participants, found that cancer survivors who tested positive for COVID-19 were nearly twice as likely to die from cancer compared to those who tested negative.
“The effect was most pronounced in the first year after infection,” said Dr Roel Vermeulen, who led the population study analysis.
In the U.S., data from the Flatiron Health database further supported the findings: female breast cancer patients who had COVID-19 were almost 50% more likely to develop lung metastases than those who did not contract the virus.
“Our findings suggest that cancer survivors may be at increased risk of metastatic relapse after common respiratory viral infections,” Vermeulen added. “It is important to note that our study focused on the period before COVID-19 vaccines were available.”
Preventive Strategies for Cancer Survivors Facing Respiratory Risk
The researchers stress this is a call for awareness—not fear. “Our findings indicate that individuals with a history of cancer may benefit from taking precautions against respiratory viruses, such as vaccination when available, and discussing any concerns with their healthcare providers,” said Dr Aguirre-Ghiso.
Future Research into Viral Triggers and Cancer Progression
The research team plans to expand their investigation to other cancer types and metastatic sites.
“By understanding underlying mechanisms, we will work hard to develop interventions that can limit the risk of metastatic progression in cancer survivors who experience respiratory viral infections,” said Dr DeGregori.
The long-term impact on cancer survivors could become a crucial public health issue, as respiratory viruses continue to circulate globally. “Respiratory viral infections are forever a part of our lives, so we need to understand the longer-term consequences of these infections,” DeGregori concluded.