A new study published in prestigious journal Nature has sent ripples through the medical community, raising urgent questions about the hidden risks faced by breast cancer survivors.

The research, led by a team at the University of Colorado and collaborating institutions, reveals a startling connection between common respiratory viruses and the reactivation of dormant breast cancer cells in the lungs. The implications are profound, touching on the lives of millions who have battled cancer and now live with the lingering fear of recurrence.

For years, the focus in breast cancer treatment has been on eradicating the primary tumour. Yet, the real threat often lies elsewhere. After successful therapy, tiny clusters of cancer cells, known as disseminated cancer cells (DCCs), can quietly settle in distant organs such as the lungs, bone or liver. These cells may remain inactive for months, years or even decades, posing no immediate danger. However, when they awaken, they can multiply rapidly, forming metastatic tumours that are responsible for the majority of breast cancer deaths.

The question of what triggers these dormant cells to spring back to life has long puzzled scientists. Inflammation has been suspected as a possible culprit, but direct evidence has been elusive. The new study bridges this gap, demonstrating that infections with respiratory viruses like influenza and COVID-19 (SARS-CoV-2) can act as a wake-up call for these hidden cancer cells.

The researchers employed sophisticated mouse models to unravel this mystery. In one model, mice genetically engineered to overexpress the HER2 oncogene in mammary tissue developed small numbers of HER2-positive DCCs in their lungs. These cells remained largely quiescent for up to a year. Another model, using a different genetic strain, showed a shorter dormancy period but confirmed the same phenomenon. A third approach involved transplanting established breast tumour cells into mice, leading to solitary DCCs in the lung.

Once the dormant cells were in place, the team introduced a sublethal dose of influenza A virus through the nose. The mice developed typical symptoms—weight loss, lung inflammation and eventual recovery. But what happened inside their lungs was anything but typical.

Within days, the number of HER2-positive cells exploded, increasing by up to a thousand-fold compared to uninfected controls. By two weeks after infection, clusters of proliferating carcinoma cells had formed, persisting for months. The same pattern emerged in other models, confirming that influenza infection could transform dormant single cells into growing micro-metastases.

To test whether this effect was unique to influenza, the scientists turned to a mouse-adapted strain of SARS-CoV-2 of COVID19. The results were strikingly similar. Infected mice showed high levels of the inflammatory cytokine interleukin-6 (IL-6) in their lungs, and the number of HER2-positive DCCs surged dramatically. When the gene for IL-6 was knocked out, the virus-driven expansion of DCCs was almost completely blocked. This pointed to IL-6 as a key mediator in the awakening process.

Delving deeper, the researchers analysed the cellular changes triggered by infection. Under normal conditions, dormant DCCs adopt a mesenchymal-like state, marked by the expression of proteins such as vimentin and maintained by the transcription factor ZFP281. After virus infection, many DCCs lost vimentin and briefly expressed epithelial markers—a hybrid phenotype—before entering rapid cell division.

RNA sequencing revealed that post-infection DCCs ramped up genes involved in collagen production, matrix remodelling, blood vessel growth and, notably, IL-6–JAK–STAT3 signalling. Laboratory experiments confirmed that IL-6 directly stimulates solitary cancer cells to multiply.

The story did not end there. The researchers discovered a second, immune-mediated phase that helped the newly awakened cancer cells survive. Analysis of immune cells in the lung weeks after infection showed the formation of organised lymphoid structures rich in CD4+ T cells and B cells, but notably sparse in CD8+ cytotoxic T cells.

When CD4+ T cells were depleted, the number of HER2-positive lesions fell by more than half. Depleting CD8+ cells had no such effect. Further experiments revealed that CD4+ T cells acquired a regulatory or memory-like phenotype, suppressing CD8+ cell activation. Removing CD4+ cells unleashed CD8+ T cells, which then produced more interferon-gamma and killed HER2-positive cancer cells more efficiently. In essence, CD4+ T cells helped keep the newly awakened metastases alive by muzzling their CD8+ counterparts.

Animal studies, while powerful, cannot prove that the same phenomenon occurs in humans. To address this, the team turned to two large human datasets. The first was the UK Biobank, a prospective study of more than half a million participants, including over 48,000 cancer survivors.

Among those who had tested positive for SARS-CoV-2 and whose primary cancer diagnosis dated back at least five years, the odds of dying from any cause—excluding recorded COVID-19 deaths—were more than 2.5 times higher than for matched cancer survivors who remained virus-negative. Deaths attributed specifically to cancer were almost twice as frequent among the infected group.

The second dataset came from the Flatiron Health database, covering nearly 37,000 women diagnosed with breast cancer. Those who developed COVID-19 after their initial diagnosis faced a 44 percent higher risk of subsequently being diagnosed with lung metastases than women who never had COVID-19. Even after adjusting for age, race, cancer subtype and comorbidities, the raised hazard ratio remained around 1.4.

These findings, while compelling, come with important caveats. Mouse-adapted influenza and SARS-CoV-2 infections may not perfectly mimic human disease, and the doses used in the laboratory are carefully controlled. Observational studies in people cannot prove cause and effect. Unmeasured factors, such as differences in healthcare access or treatments delayed by COVID-19, might partly contribute to the higher mortality and metastasis rates. The UK Biobank cohort skews older and healthier than the general population, while the Flatiron data do not capture undiagnosed COVID-19 cases among the negative group.

Moreover, the study focused primarily on breast cancer models and lung metastasis. Whether other dormant cancer cells in bone or liver, or disseminated cells from different tumour types, behave in the same way remains to be seen. The researchers acknowledge these limitations and call for further studies to explore the broader relevance of their findings.

Despite these uncertainties, the implications are clear. Seasonal influenza affects over a billion people each year, and the SARS-CoV-2 pandemic has recorded more than 770 million confirmed COVID-19 cases so far. If even a fraction of cancer survivors harbour dormant cells that can be stirred into life by respiratory viruses, the public health impact could be significant.

What can be done to mitigate this risk? For individuals, the simplest step is to reduce the chance of infection. Vaccination against influenza and COVID-19 remains the first line of defence. Good hand hygiene, wearing masks in high-risk settings and avoiding close contact with sick individuals are sensible precautions, especially for those with a history of cancer. Clinicians may need to heighten follow-up monitoring in the weeks and months after a significant respiratory infection.

On the research front, the role of IL-6 offers a potential therapeutic target. Several drugs that block the IL-6 receptor, such as tocilizumab, or inhibit downstream JAK–STAT signalling, are already in clinical use for inflammatory diseases and have been tested in severe COVID-19. Could a carefully timed dose of such agents during a respiratory infection protect against DCC awakening without compromising the body’s ability to clear the virus? Designing trials to test this hypothesis safely will be challenging but could pay dividends in preventing metastatic relapse.

The study also opens new avenues for understanding the complex interplay between inflammation, immunity and cancer recurrence. It highlights the need for a fresh lens on cancer survivorship, recognising that the journey does not end with the eradication of the primary tumour. Dormant cancer cells may lie in wait for years, and a seemingly innocuous bout of flu or COVID-19 could be enough to rouse them from their slumber, with potentially deadly consequences.

As we enter each new season of respiratory viruses, these findings serve as a timely reminder that vigilance against infections is not just about avoiding a few days of discomfort. For cancer survivors, it may be a crucial step in keeping hidden dangers at bay. The research underscores the importance of preventive measures, ongoing monitoring and the development of new strategies to protect those at risk.

The medical community will undoubtedly be watching closely as further studies unfold. The link between respiratory viruses and metastatic cancer is a new frontier, one that demands attention, innovation and collaboration. For now, the message is clear: protecting cancer survivors from common infections is more important than ever.

The study published offers a compelling narrative that connects two of medicine’s most pressing challenges—respiratory viruses and metastatic cancer. It provides a scientific foundation for renewed efforts in prevention, monitoring and therapy.

The journey to lasting cancer freedom may be winding, but with vigilance and continued research, the path can be made safer for all.