Smoking May Increase Risk for Breast Cancer in Postmenopausal Women

Laurie Barclay, MD

March 09, 2011

March 9, 2011 — Smoking is linked to an increased risk for breast cancer in postmenopausal women, according to the results of a prospective cohort study reported in the February 28 issue of the BMJ.

"The detection of smoking-specific DNA adducts and mutations in the p53 gene in the breast tissue of smokers supports the biological plausibility of a positive association between cigarette smoking and breast cancer," write Juhua Luo, from West Virginia University in Morgantown, and colleagues. "Despite this mechanistic evidence, systematic reviews of epidemiological studies published as of 2002 concluded that there was no overall association between active smoking and breast cancer risk, and attributed conflicting results of individual studies in part to the confounding effects of alcohol. However, recent reappraisals of evidence from recent cohort studies have suggested an increased risk of breast cancer that is independent of the effects of alcohol among women who smoked cigarettes for a long period of time or who started smoking at a young age."

The goal of the study was to evaluate the association between smoking and the risk for invasive breast cancer in postmenopausal women, using quantitative measures of lifetime exposure to passive and active smoking. At 40 clinical US centers, 79,990 women aged 50 to 79 years were enrolled in the Women's Health Initiative Observational Study during the period from 1993 to 1998. The primary study endpoint was pathologically confirmed, invasive breast cancer as a function of self-reported active and passive smoking.

During follow-up of average duration 10.3 years, there were 3520 incident cases of invasive breast cancer. Compared with never-smokers, former smokers had a 9% increase in breast cancer risk (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.02 - 1.17), and current smokers had a 16% increase in breast cancer risk (HR, 1.16; 95% CI, 1.00 - 1.34).

Active smokers with high intensity and duration of smoking, as well as those who began smoking when they were teenagers, had significantly higher breast cancer risk. Women who had smoked for at least 50 years had the highest risk for breast cancer (HR, 1.35; 95% CI, 1.03 - 1.77) vs all lifetime nonsmokers (HR, 1.45; 95% CI, 1.06 - 1.98) and vs lifetime nonsmokers with no exposure to passive smoking. After stopping smoking, the risk for breast cancer remained increased for up to 20 years.

The most extensive exposure to passive smoking was considered to be at least 10 years' exposure in childhood, at least 20 years' exposure as an adult at home, and at least 10 years' exposure as an adult at work. Among women who had never smoked, those with the most extensive exposure to passive smoking had a 32% increased risk for breast cancer vs those who had never been exposed to passive smoking (HR, 1.32; 95% CI, 1.04 - 1.67), after adjustment for potential confounders. Other groups with lower exposure to cumulative passive smoking had no significant association with breast cancer risk, nor was there any apparent dose response to cumulative passive smoking exposure.

"Active smoking was associated with an increase in breast cancer risk among postmenopausal women," the study authors write. "There was also a suggestion of an association between passive smoking and increased risk of breast cancer."

Limitations of this study are use of only baseline values for women's smoking status and all covariates, inability to account for changes in exposure during follow-up, possible recall bias regarding passive smoking exposure in childhood, and lack of data regarding the intensity or frequency of passive smoke exposure.

"Our findings highlight the need for interventions to prevent initiation of smoking, especially at an early age, and to encourage smoking cessation at all ages," the study authors conclude. "Future studies examining how genetic polymorphisms and other risk factors modify the effect of tobacco exposure on breast cancer risk are likely to further our understanding of this important issue."

Editorial: More Study Limitations

In an accompanying editorial, Paolo Boffetta, from Tisch Cancer Institute and Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, NY, and Philippe Autier, from International Prevention Research Institute in Lyon, France, note additional study limitations of potential confounding by working status and by drinking alcohol.

"Overall, Luo and colleagues' analysis supports the hypothesis that smoking increases the risk of breast cancer, in particular when the habit starts early in life," Drs. Boffetta and Autier write. "These data, however, should be placed in the context of the overall evidence, and in particular the results of a pooled analysis of 10 cohort studies and 43 case-control studies, which found no increased risk in either group of studies. In the case of secondhand smoke, the evidence can still be considered suggestive of an association at best."

The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services. The study authors and editorialists have disclosed no relevant financial relationships.

BMJ. 2011;342:d1016, d1093. Full text Full text

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