A recent study looked at an understudied link between metastatic breast cancer and respiratory viruses.

It found that the inflammation caused by the influenza and SARS‑CoV‑2 viruses can trigger cancer metastasis in laboratory mice.

Cancer cells can detach from their original tumors and travel to different parts of the body. Far away from their original location, these disseminated cancer cells (DCC) can grow into new tumors.

DCCs can remain dormant for years or decades, long after the original tumor was removed, before awakening and becoming tumors. We do not know the cause of this exodus of cells or the reasons they awaken and reactivate.

These new findings begin to explain this phenomenon. Studies have demonstrated that cancer metastasis can be triggered by inflammation. Infection by respiratory viruses, such as the flu and SARS‑CoV‑2, usually causes inflammation.

A team of researchers led by Dr. James DeGregori at the University of Colorado Anschutz Medical Campus wanted to find out if respiratory virus infections could cause DCC awakening. They used breast cancer models in mice to study the effects of the flu and SARS‑CoV‑2 infection on DCCs and lung metastasis.

The study was published in the journal Nature on July 30, 2025.

Before infection, the mice’s lungs contained only a small number of isolated DCCs. Three days after they were infected by the flu or influenza virus, a notable increase in the number of DCCs was observed in their lungs. This number continued to rise over two weeks and remained elevated even nine months after infection. As the number of DCCs increased, the proportion of DCCs in the dormant stage decreased.

Scientists observed similar effects in mice infected by SARS‑CoV‑2 in the laboratory, explains a review of this study published in NIH Research Matters.

Subsequent studies demonstrated that virus‑induced activation of DCCs required the inflammatory signaling molecule Interleukin 6 (IL‑6). Mice that could not produce IL‑6 showed much less DCC growth and a greater proportion of dormant DCCs in their lungs after flu infection. Additionally, organoids formed from the mice’s mammary glands grew significantly after treatment with IL‑6.

The team observed that DCCs tended to cluster near immune cells called CD4+ T lymphocytes. Depletion of CD4+ T lymphocytes reduced the number of DCCs that remained awake one month after infection. It also increased the number of CD8+ T lymphocytes, which destroy cancer cells and virus‑infected cells, in the lungs. CD8+ T lymphocytes in CD4+ T lymphocyte‑depleted mice were more effective at destroying breast cancer cells.

This suggests that CD4+ T lymphocytes help awaken DCCs by suppressing the activity of CD8+ T lymphocytes.

The scientists then translated the observations gathered from data collected in mice to the real world.

They analyzed the association between SARS‑CoV‑2 infection, cancer progression, and mortality in electronic medical records in the United Kingdom Biobank from almost 5,000 people who had a prior cancer diagnosis and were inferred to be in remission. In this population, a positive test for SARS‑CoV‑2 almost doubled the risk of death from cancer.

In a separate dataset of over 36,000 women with breast cancer, having COVID‑19 increased the risk of lung metastasis by approximately 40%.

The findings suggest how respiratory virus infections can contribute to the risk of cancer recurrence and metastasis. They also point to potential pathways for interventions that could reduce this risk.

As Dr. DeGregori put it simply, “Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames.”

Breast cancer is the second most common cancer worldwide, and most deaths (of which there were about 670,000 in 2022) are caused by metastatic disease, often after long periods of clinical dormancy.