Smoking Effect on Pulmonary Metastasis from Breast Cancer

Institution: University of California, Davis
Investigator(s): Susan Murin, M.D. -
Award Cycle: 2001 (Cycle VII) Grant #: 7IB-0049 Award: $74,968
Award Type: IDEA
Research Priorities
Biology of the Breast Cell>Pathogenesis: understanding the disease

Initial Award Abstract (2001)
Smokers are more likely to die of breast cancer than are non-smokers, though they donít get breast cancer any more often. This suggests that breast cancer may behave more aggressively among smokers. The reasons for this are not clear. Studies with animals have shown that a variety of things that injure the lung, like exposure to high concentrations of oxygen or to radiation, do increase metastasis to the lung. Because smoking also injures the lung, we think it may make breast cancer more likely to spread to the lung, but this has not been directly studied. Studies in populations of patients have suggested that smoking may encourage the spread of breast cancer to the lungs, but these types of studies can only indirectly look at the association between smoking and breast cancer behavior. We propose to examine the relationship between smoking and the spread of breast cancer to the lungs more directly, in an animal model of breast cancer.

We will study the effect of smoking on the spread of breast cancer to the lung by measuring the number and size of breast cancer deposits in the lung among mice exposed to cigarette smoke compared to mice not exposed to cigarette smoke. The experiments will be carried out using specialized smoke-exposure chambers that generate smoke concentrations that are comparable to those experienced by actively smoking adults. The breast cancer model in the mice is one that is very much like the human situation and that has previously been used to answer other questions about things that affect the spread of breast cancer, such as diet. We will compare both smoking and non-smoking animals, as well as a third group of animals that stops smoking after the breast cancer has grown for awhile. We include this third group because it allows us to model the situation of a woman quitting smoking at the time her breast cancer is diagnosed. If smoking does cause breast cancer to spread more easily, it will be important to see if this effect can be prevented by a woman quitting smoking when she finds out about her cancer.

Since breast cancer and smoking are both very common among women an effect of smoking on the behavior of breast cancer is potentially quite important. This is especially true if the adverse effect of smoking can be reversed by quitting smoking at the time of breast cancer diagnosis. Even if it can not be reversed, it is still important. Women smokers may be persuaded to quit smoking if they know it will make them more likely to die should they get breast cancer. Also, studies that compare women with breast cancer will need to take their smoking status into account if smoking really does make a difference in the way breast cancer behaves.

Final Report (2003)
Women who smoke are more likely to die of breast cancer than non-smoking women. There is some evidence that breast cancer may be more likely to spread (metastasize) to the lungs of women who smoke, which could contribute to their increased rate of death from breast cancer. To determine whether there is a biological basis for this observation in women, we investigated the effect of cigarette smoke exposure upon the spread of breast cancer cells to the lungs of mice.

We demonstrated that mice exposed to cigarette smoke had an increase in the total amount of breast cancer that metastasized to their lungs compared with animals exposed only to room air. This increase was statistically significant. This increase was largely due to an increase in the number of cancer nodules that developed in their lungs; the nodules were not larger than those of non-exposed animals. We also saw a trend toward a lesser cancer burden in the lungs of mice whose exposure to cigarette smoke was stopped at the time they were injected with cancer cells compared with those mice who continued being exposed to smoke. The effect was not statistically significant in this small group.

This study provides direct, experimental evidence that exposure to cigarette smoke is associated with an increase in the spread of cancer cells to the lung. This suggests one possible way to explain the higher breast cancer death rate observed among smoking women. It highlights the need for smoking cessation efforts directed at women, particularly those at increased risk of breast cancer. In future investigations, we plan to study the way(s) in which cigarette smoke exposure causes an increase in metastasis of breast cancer to the lungs, and see if the effects can be modified.

The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer
Index Medicus: Chest
Authors: Murin S, Pinkerton KE, Hubbard NE, Erickson K
Yr: 2004 Vol: 125 Nbr: 4 Abs: Pg:1467-71