Apr. 17, 2007 An intriguing study, conducted in mice and supported by an ongoing examination of breast cancer patient records, suggests a link between the pulmonary inflammation seen in asthma and increased risk of lung metastasis.
The study, conducted by researchers at Mayo Clinic Arizona, suggests that breast cancer patients who have asthma could reduce their risk of cancer spread by using readily available inhaler medications.
"A link between pulmonary inflammation and lung metastasis would not only have significant effects on patient diagnosis and care, but will also immediately affect the way breast cancer patient are treated," said Anna Taranova, M.D., a senior research fellow in the laboratory of James Lee, Ph.D. at Mayo. "Those with asthma might be able to reduce their risk of lung metastasis, and increase their survival, with aggressive corticosteroid treatment."
Furthermore, the findings could prove to be relevant to asthma patients diagnosed with other cancers that metastasize to the lungs, according to Dr. Taranova. "We suspect that the relationship between lung inflammation and metastasis will not be limited to breast cancer patients," Dr. Taranova said.
The researchers say these results, along with findings from their other recent research, offer a biological link: activation of cells that line blood vessels is required both for the movement of pro-inflammatory white blood cells into lung tissue (as occurs in asthma) and for the movement of circulating cancer cells from the blood into lung tissue.
In this study, mice were exposed to an aerosolized allergen commonly used in mouse asthma studies and then were injected with melanoma cells. Three other groups of mice were also studied: control mice; mice that received the human corticosteroid allergy and asthma therapeutic agent budesonide after exposure to the allergen; and mice treated with an antibody to eliminate CD4+ T cells before exposure to allergen. (CD4+ T cells orchestrate immune responses to allergens and are largely responsible for the lung inflammation that occurs in asthma.) Metastasis was continually assessed in all groups.
The researchers found that allergen-induced pulmonary inflammation was associated with an almost 400 percent increase in lung metastasis in the mice. But in mice treated with either an antibody to deplete CD4+ T-cells or budesonide to reduce their allergic lung inflammation, the rate of metastasis fell to that seen in mice that were not exposed to allergen. "The treatments wiped out the increases in the rate of metastasis induced by allergic inflammation, reducing the observed rates of metastasis to those found in mice that never experienced the allergen," Dr. Taranova said.
The researchers are now working with epidemiologists at Mayo Clinic Rochester to determine if breast cancer patients with lung metastasis had higher than normal rates of asthma. To date, they have found "productive and provocative results," Dr. Taranova says: over 20 percent of women with breast cancer who developed lung metastasis also appear to have had a previous diagnosis of asthma. The typical frequency of asthma occurrence in U.S. women is, at most, eight percent, she said.
"Our long term goal is to continue this detailed retrospective study of breast cancer patients, eventually translating these studies into a multi-center prospective examination of cancer patients," Dr. Taranova said. "We want to define the specific parameters that link lung metastasis and pulmonary disease."
The researchers say that many questions need to be answered, including whether asthmatics who regularly use anti-inflammatory corticosteroids experience a side benefit of reduced risk for lung metastasis, and whether people who have allergies, but not asthma, are at the same risk.
Dr. Taranova believes these findings are surprising, as the researchers originally suspected that patients with asthma would have limited lung metastasis. "However, as in most things in science, we have learned much more from studies disproving our flawed hypotheses than from studies confirming our preconceived ideas," she said.
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