Asthma and Related Tissue Inflammation May Contribute to Cancer Metastasizing to Lung

Nick Mulcahy

October 22, 2008

October 22, 2008 — Controlling tissue inflammation of the lungs related to asthma might help prevent the metastasis of cancer to the lung, according to a new animal-model study that has potentially important implications for the management of cancer patients.

"It appears that inflammation changes the lung environment, encouraging the recruitment of circulating [cancer] cells [into the lungs]," said study coauthor Jamie J. Lee, PhD, associate professor of biochemistry and molecular biology at the Arizona campus of the Mayo Medical School, in Scottsdale.

In an interview with Medscape Oncology, Dr. Lee advised that "aggressive treatment" of asthma may have a "considerable effect" on the survival of patients with solid tumors by preventing lung metastases.

Dr. Lee's observations and recommendations come from studies of mice in which he and colleagues identified the localized tissue inflammation associated with asthma as a potentially significant contributor to lung metastasis; they also show that inhaled corticosteroids can prevent the event. Additionally, the researchers performed a small retrospective review of a breast cancer surgical patient database that suggested that a relationship between asthma and lung metastasis may exist in humans.

The study's conclusion that lung-tissue inflammation contributes to lung metastasis makes such good sense, said Dr. Lee, that scientists from other disciplines have expressed wonder to him that "no one else figured this out."

The research, which was published in the October 15 issue of Cancer Research, obviously needs additional and more detailed studies of patients, said Dr. Lee.

Mouse-Model Studies Show Possible Link

The new mice studies showed that, in mice injected with cancer cells, allergen-induced pulmonary inflammation resulted in a greater than 3-fold increase in lung metastases.

"The present study identifies allergic pulmonary inflammation as a potential contributing factor in the process by which the lung is a selected target of circulating cancer cells," write the study authors.

Furthermore, interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the pulmonary recruitment of cancer cells from circulation, they write.

"We have shown the following in the mouse model: if you treat patients with inhaled corticosteroids, you can reduce asthma symptoms and drop the level of lung metastases back to normal or baseline," explained Dr. Lee.

Hidden in Plain View

In establishing a possible link between tissue inflammation of the lungs and lung metastasis, the researchers made an observation about the lungs and cancer that other specialists found unusual for not having been previously uncovered, said Dr. Lee. "I've had both pulmonologists and oncologists comment to me: 'How did we miss that?'," he said.

Dr. Lee believes the link has never been made before because clinical trials regularly exclude patients with confounding health issues. So, in a cancer study, patients with asthma will be excluded and, in an asthma study, patients with cancer are, of course, excluded. Dr. Lee also observed that chemotherapy for cancer will improve asthma wheeze, which obscures the fact that some patients in cancer trials will have the condition but, by chance, will not have been excluded.

As basic scientists, Dr. Lee and his team are "not hamstrung" by having to deal with patients in a single-focused manner, he explained. Meanwhile, specialists and their clinical trials have been like "ships passing in the night" with regard to seeing this other "ship" — the likely link between lung-tissue inflammation and the metastasis of solid tumors to the lung.

Not Limited to Patients with Asthma or Breast Cancer

"This link may not be asthma-specific," noted Dr. Lee. "Other conditions or circumstances, such as pollution or chronic respiratory infections, can create the same inflammatory effect and allow circulating cancer cells to enter the lungs."

He also said that "there was no reason to believe that the link is specific to breast cancer," because all cancer cells circulate in the body. However, Dr. Lee and his team "enhanced" the significance of their findings by examining the Mayo Clinic Surgical Breast Cancer Database, a set of patients treated with surgery at the clinic since 1988. The database includes information on recurrence. The cohort from the database used in this study was 176 patients with distant metastases to the lung.

Of the 176 patients, 30 had a diagnosis of asthma and at least 23 were identified with asthma 1 year before the spread of cancer to the lung. Thus, the percent of women with asthma (13%) in the lung-metastases cohort was nearly twice the predicted frequency of asthma in a random population of women in the United States (7%–8%), the authors note. The difference in rates suggests "that the asthma of these cancer patients may have contributed to the appearance of lung metastases," they write. Also, importantly, the database records indicate that only 2 of the 23 patients had any indication of inhaled corticosteroid use. "The solution to this problem in cancer patients may be simple," summarized Dr. Lee. "If you have asthma, you need to be taking inhaled corticosteroids in a compliant way."

The researchers have disclosed no relevant financial relationships.

Cancer Res. 2008; 68:8582-8589. Abstract

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