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Communications to the Editor |

Breast Cancer in Smokers FREE TO VIEW

Harry W. Daniell
Author and Funding Information

Affiliations: University of California, Davis, Medical School Redding, CA,  University of California, Davis, School of Medicine Sacramento, CA

Correspondence to: Harry W. Daniell, MD, Clinical Professor of Family Practice, University of California Davis Medical School, 2626 Edith Ave, Redding, CA 96001



Chest. 2003;123(5):1771-1772. doi:10.1378/chest.123.5.1771
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To the Editor:

The observation by Murin and Inciardi (June 2001)1 of increased pulmonary metastases from breast cancer among smokers is supported by more evidence than they included in their article. This evidence also helps to discount the possibility of coincidence as posed by Lillington and Sachs (June 2001)2 and answers some of the questions posed by the authors of both publications.

In a study of 485 postmenopausal women, we found more frequent axillary metastases among smokers than among nonsmokers after control for age, estrogen receptor status, primary tumor size, and obesity.3 In a separate series of 176 women with axillary metastases,4 we found that metastases were larger in smokers (p < 0.01) after control for primary tumor size, obesity, the number of positive nodes, and host age. Primary tumors were slightly smaller in smokers, evidence against delayed tumor diagnosis among them. These observations are most compatible with earlier and more frequent metastasis by breast cancer cells in smokers, and they are also compatible with more rapid growth of breast cancer metastases among them.

Murin and Inciardi1 did not report whether smokers in their study demonstrated more axillary nodes than otherwise similar nonsmokers, but this data would be of interest.

The phenomenon of more frequent metastases from primary tumors in smokers, or of more rapid progression of primary or metastatic tumor tissue in them, was referenced by Murin and Inciardi in patients with myelogenous leukemia, prostate cancer, and malignant melanoma. This phenomenon is not restricted to these tumor types, having also been documented in patients with carcinomas of the endometrium,5 cervix,6 bladder,7 lung,8 and colon,9 as well as those with breast cancer. Most metastases from these tumors are nonpulmonary, indicating the presence of smoking-related systemic factors, which either directly stimulate malignant cells or inhibit host antitumor defense mechanisms, resulting in accelerated growth, invasion, or metastasis by these cells. The probability of smoking-induced inhibition of host antitumor immune defenses was recognized by Murin and Inciardi and is supported by evidence documenting widespread impairment of immune responses in smokers,10 including the easily measured responses to vaccines against influenza11 and hepatitis B.12 Most tumor types with smoking-associated worse prognosis are not hormone sensitive, suggesting that smoking-induced endocrine abnormalities cannot explain this general pattern. The possibility of increased pulmonary metastases having resulted from direct influence on pulmonary tissue by tobacco smoke seems remote.

References

Murin, S, Inciardi, J (2001) Cigarette smoking and the risk of pulmonary metastasis from breast cancer.Chest119,1635-1640. [PubMed] [CrossRef]
 
Lillington, GA, Sachs, DP Cigarette smoking, pulmonary metastases, and breast carcinoma: coincidence or causality?Chest2001;119,1627-1628. [PubMed]
 
Daniell, H Increased lymph node metastases at mastectomy for breast cancer associated with host obesity, cigarette smoking, age, and large tumor size.Cancer1988;62,429-435. [PubMed]
 
Daniell, H, Tam, E, Filice, A Larger axillary metastases in obese women and smokers with breast cancer: an influence by host factors on early tumor behavior.Breast Cancer Res Treat1993;25,193-201. [PubMed]
 
Daniell, H More advanced-stage tumors among smokers with endometrial cancer.Am J Clin Pathol1993;100,439-443. [PubMed]
 
Kucera, H, Enzelsberger, H, Eppel, W, et al The influence of nicotine abuse and diabetes mellitus on the results of primary irradiation in the treatment of carcinoma of the cervix.Cancer1987;60,1-4. [PubMed]
 
Thompson, IM, Peek, M, Rodriguez, FR The impact of cigarette smoking on stage, grade, and number of recurrences of transitional cell carcinoma of the bladder.J Urol1987;137,401-403. [PubMed]
 
Hinds, MW, Yang, H-Y, Stemmerman, G, et al Smoking history and lung cancer survival in women.J Natl Cancer Inst1982;68,395-399. [PubMed]
 
Daniell, HW More advanced colonic cancer among smokers.Cancer1986;58,784-787. [PubMed]
 
Burton, RC Smoking, immunity, and cancer.Med J Aust1983;2,411-412. [PubMed]
 
Finklea, JF, Hasselblad, V, Riggan, WB, et al Cigarette smoking and hemagglutination inhibition response to influenza after natural disease and immunization.Am Rev Respir Dis1971;104,368-376. [PubMed]
 
Hollinger, FB Factors influencing the immune response to hepatitis B vaccine, booster dose guidelines, and vaccine protocol recommendations.Am J Med1989;87,36S-40S
 
To the Editor:

I am very pleased to comment upon Dr. Daniell’s very scholarly response to our article. His work on prostate cancer and smoking was referenced in our article. I appreciate his bringing to my attention his earlier, related work examining the relationship between smoking and the natural histories of breast and colon cancers. Those studies provide further evidence of an effect of smoking upon the biological behavior of malignancies for which a causal association with smoking has not been established. I agree with Dr. Daniell that systemic effects of smoking, particularly but not limited to immunologic effects, may explain the relationship between smoking and a greater propensity to metastasis. However, I also believe a direct effect of smoking upon the lung to be another, very plausible, contributing factor. In our study, we found that the relationship between smoking and metastatic disease was strongest, in fact, for the subgroup of patients with known metastases limited only to the lung. We have recently validated an animal model of the effects of smoking upon breast cancer metastasis to the lung, and we look forward to employing this model to help clarify the mechanisms involved. As for the issue of hormonal effects of smoking, I agree with Dr. Daniell that, while smoking does have minor hormonal effects, those effects are unlikely to explain the effects of smoking upon metastasis. This possibility was included at the request of the reviewers of the manuscript.

In answer to his one specific question about our work, we employed a matched, case-control study design, and axillary lymph node status was one of the factors for which we matched cases and controls. Thus, it is not possible to compare the nodal status for smokers and nonsmokers in our database, which was, by design, the same for both groups


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References

Murin, S, Inciardi, J (2001) Cigarette smoking and the risk of pulmonary metastasis from breast cancer.Chest119,1635-1640. [PubMed] [CrossRef]
 
Lillington, GA, Sachs, DP Cigarette smoking, pulmonary metastases, and breast carcinoma: coincidence or causality?Chest2001;119,1627-1628. [PubMed]
 
Daniell, H Increased lymph node metastases at mastectomy for breast cancer associated with host obesity, cigarette smoking, age, and large tumor size.Cancer1988;62,429-435. [PubMed]
 
Daniell, H, Tam, E, Filice, A Larger axillary metastases in obese women and smokers with breast cancer: an influence by host factors on early tumor behavior.Breast Cancer Res Treat1993;25,193-201. [PubMed]
 
Daniell, H More advanced-stage tumors among smokers with endometrial cancer.Am J Clin Pathol1993;100,439-443. [PubMed]
 
Kucera, H, Enzelsberger, H, Eppel, W, et al The influence of nicotine abuse and diabetes mellitus on the results of primary irradiation in the treatment of carcinoma of the cervix.Cancer1987;60,1-4. [PubMed]
 
Thompson, IM, Peek, M, Rodriguez, FR The impact of cigarette smoking on stage, grade, and number of recurrences of transitional cell carcinoma of the bladder.J Urol1987;137,401-403. [PubMed]
 
Hinds, MW, Yang, H-Y, Stemmerman, G, et al Smoking history and lung cancer survival in women.J Natl Cancer Inst1982;68,395-399. [PubMed]
 
Daniell, HW More advanced colonic cancer among smokers.Cancer1986;58,784-787. [PubMed]
 
Burton, RC Smoking, immunity, and cancer.Med J Aust1983;2,411-412. [PubMed]
 
Finklea, JF, Hasselblad, V, Riggan, WB, et al Cigarette smoking and hemagglutination inhibition response to influenza after natural disease and immunization.Am Rev Respir Dis1971;104,368-376. [PubMed]
 
Hollinger, FB Factors influencing the immune response to hepatitis B vaccine, booster dose guidelines, and vaccine protocol recommendations.Am J Med1989;87,36S-40S
 
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