How Respiratory Viruses Can Reactivate Dormant Breast Cancer Cells in the Lungs？

Breast cancer remains one of the most prevalent malignancies among women worldwide, with metastatic disease representing a significant challenge to patient survival and quality of life. Recent research indicates that ​respiratory viral infections​, such as influenza and SARS-CoV-2, can play a crucial role in the ​reawakening of dormant metastatic breast cancer cells in the lungs​. Understanding these interactions is vital for developing effective treatment strategies and improving patient outcomes. This review synthesizes key findings on how respiratory infections influence ​breast cancer metastasis​, focusing on mechanisms that disrupt dormancy in disseminated cancer cells (DCCs) and the potential implications for clinical practice.

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What Did the Study Actually Show?

In August 2025, researchers published a study in Nature (Nature article) using mouse models of breast cancer to investigate how dormant disseminated tumor cells (DTCs) respond to ​respiratory viral infections​. The findings were striking: dormant cells didn’t merely stir—they re-entered the cell cycle and formed macroscopic metastases in the lungs.

Mechanistically, viral infection triggered inflammatory signaling cascades that disrupted the so-called ​pro-dormancy phenotype​. Immune cells, usually tasked with restraining these dormant cells, became preoccupied fighting the infection. Cytokines such as IL-6 and interferon-γ surged, reshaping the tumor microenvironment to favor cell proliferation.

This wasn’t a minor blip. Both influenza A and SARS-CoV-2 infections led to significant increases in metastatic burden compared to controls.

You know what’s fascinating? This reinforces a central idea in cancer biology: ​systemic inflammation can be a double-edged sword​. It may suppress tumor initiation in some contexts but, paradoxically, can reactivate dormant cells in others.

How Do Dormant Cancer Cells Actually Behave?

Dormant breast cancer cells are almost ghost-like. After leaving the primary tumor, some disseminated tumor cells enter a quiescent state—neither dividing nor causing harm, essentially invisible to the immune system.

Picture them as ​sleeping spies​—hiding behind enemy lines, awaiting the right signal to wake up. That trigger could be tissue injury, hormonal shifts, or, as this study shows, ​viral infections​.

Dormancy depends on a delicate balance of ​integrins, angiogenic signals, and immune surveillance​. When inflammation tips this balance, cells that once lay hidden decide it’s time to grow.

It’s ironic: the immune system, meant to defend the body, can unintentionally give cancer cells the green light during systemic infections.

Could This Phenomenon Occur in Humans?

Here’s the caveat. ​All direct evidence comes from mice​. No clinical study has yet confirmed that catching influenza or COVID-19 will definitively awaken dormant breast cancer cells in humans.

Yet, epidemiological data suggest correlations. Retrospective analyses indicate that ​infections sometimes coincide with cancer relapse​, though proving causation is challenging. Variables like patient age, immune status, and tumor subtype complicate interpretations.

Still, it’s plausible. Dormant breast cancer cells have been detected ​years—even decades—after primary treatment​. The immune system keeps them in check… until some event tilts the balance. Respiratory infections are prime suspects because the lung is a frequent metastatic site for breast cancer.

Think of it like a detective story: fingerprints, footprints, and a few eyewitnesses—but no smoking gun. This paper adds another piece to the puzzle.

Clinical Implications for Patients

First, context matters. This isn’t a reason to panic at every cough. The research is preliminary; no clinical guidelines have changed.

Still, it raises important considerations:

• Monitoring for recurrence becomes even more critical if dormant cells can “wake up.”
• Vaccination against influenza and COVID-19 reduces serious illness and may indirectly lower systemic inflammation, which could theoretically influence dormancy.

Symptoms of secondary breast cancer in the lung may include:

• Persistent cough or wheezing
• Shortness of breath
• Chest pain
• Unexplained fatigue

(Source: Cancer Research UK)

These symptoms aren’t unique to metastasis, but ​any new or persistent changes should prompt evaluation​.

Long-term, research may develop drugs that reinforce dormancy or block pro-inflammatory pathways during infections. Labs are already exploring immune-modulating therapies to prevent dormant cells from reactivating.

Integration with Broader Cancer Research

Cancer dormancy is a hot topic. Key questions include:

• Why do some cells remain dormant while others proliferate immediately?
• Can we ​force tumors into permanent dormancy​?
• What triggers reactivation—and how can we prevent it?

Interestingly, not all viruses are harmful in this context. Oncolytic viruses are engineered to kill cancer cells rather than awaken them. Context matters: immune responses can act as protectors or accidental enablers.

This finding does not overturn established cancer biology but adds nuance. The immune system’s role is ​situational​, not purely protective or harmful.

Future Research Directions

Upcoming studies are likely to focus on:

• Lineage tracing to track which dormant cells reactivate
• Single-cell sequencing to identify molecular switches
• Immune profiling to understand which cells lose control during infection

Clinical research will probably begin with ​retrospective analyses of breast cancer cohorts​, correlating viral infections with recurrence timing. Strong signals may lead to prospective trials testing anti-inflammatory or antiviral interventions.

The lab work is painstaking—infecting mice with flu and SARS-CoV-2 under controlled conditions involves long hours, careful tissue processing, and rigorous statistics. But the potential insights make the effort worthwhile.

How PubMed.ai Accelerates Research

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• Searching smarter: natural language queries for precise results
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For researchers exploring how infection, immunity, and metastasis intersect, PubMed.ai can transform hours of reading into actionable insight in minutes.

FAQs

What are dormant breast cancer cells, and why are they dangerous?

Dormant cells are disseminated tumor cells that remain inactive for years. They can suddenly resume growth, leading to metastatic disease long after primary treatment.

Can respiratory infections trigger metastatic breast cancer relapse?

Mouse studies suggest it’s possible. Human data are less direct but indicate systemic inflammation from infections may create conditions that awaken dormant cells.

What symptoms indicate secondary breast cancer in the lungs?

Persistent cough, wheezing, shortness of breath, chest pain, and unexplained fatigue. Persistent changes should prompt medical review.

Is this research relevant for COVID-19 survivors?

Potentially. SARS-CoV-2 was included in animal studies, suggesting that survivors with prior breast cancer may have altered recurrence risks.

What future treatments could keep cancer cells dormant?

Potential strategies include microenvironment-stabilizing drugs, anti-inflammatory therapies, and immune-modulating treatments to maintain dormancy.