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Date of release: 16 May, 2011

Cigarette smoking and the incidence of breast cancer


A recent paper, published by Xue and colleagues in the Archives of Internal Medicine, looked at the association between active or passive smoking and breast cancer risk among the Nurses’ Health Study cohort [1]. The Nurses’ Health Study is a prospective cohort study of 111,140 participants followed up from 1976 to 2006 for active smoking and 36,017 women followed from 1982 to 2006 for passive smoking. The study was based on biennial questionnaires, which included data on smoking and other clinical characteristics. During 3,005,863 person-years of follow-up, 8772 incident cases of invasive breast cancer were reported. After adjustment for potential confounders, the hazard ratio (HR) of breast cancer was 1.06 (95% confidence interval (CI) 1.01–1.10) for ever-smokers relative to never-smokers. Body mass index did not modify the HR, and there was a marginally significant increase in breast cancer risk with increasing number of pack-years of smoking. Heavy smokers (measured by an index that integrates having started smoking at < 18 years of age, having smoked for > 35 years and smoking > 25 cigarettes/day) had a HR of 1.25 (95% CI 1.06–1.46). Also, smoking before the first birth was associated with an increased risk. Every increase of 20 pack-years of smoking after menopause was associated with a decrease of breast cancer risk in non-users of hormone therapy when adjusted for the covariates (p < 0.001) but this was not seen in hormone users. The positive association between smoking and breast cancer risk concerned estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors. There was also a small association of continuous passive smoking with breast cancer risk (HR 1.08, 95% CI 1.03–1.12) but not for intermittent passive smoking at work or at home and exposure to parental smoking. 


 


Another paper from the Women’s Health Initiative (WHI) observational study was also recently published on the same topic and showed similar results [2]. The cohort consisted of 79,990 women aged 50–79 years who were enrolled in the WHI observational study during 1993–1998. All information on exposure and confounders used in the analysis was collected at baseline. Active and passive smoking were self-reported and invasive breast cancer was confirmed pathologically. In this cohort, 3520 incident cases of invasive breast cancer were identified during an average 10.3 years of follow-up. The risk of breast cancer was increased in former and current smokers (HR 1.09, 95% CI 1.02–1.17; HR 1.16, 95% CI 1.00–1.34, respectively). The risk also correlated with the intensity and duration of smoking. The highest breast cancer risk was found among women who had smoked for ≥ 50 years (HR 1.35, 95% CI 1.03–1.77 compared with all lifetime non-smokers; HR 1.45, 95% CI 1.06–1.98 compared with lifetime non-smokers with no exposure to passive smoking). The increased risk was only significant for ER-positive tumors, PR-positive tumors and lobular breast cancer. Smoking before the first full-term pregnancy was also associated with a greater increase in the risk. An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Intensive passive exposure was associated with an increased risk.

Comment

Carcinogens from cigarettes can increase the risk of breast cancer but, conversely, smoking seems to have anti-estrogenic effects which may potentially reduce this risk. Systematic reviews of epidemiological studies published before 2002 concluded that there was no overall association between active smoking and breast cancer risk, suggesting that the associations could be due to a confounding factor, alcohol consumption. More recently, however, positive associations have been reported among heavy smokers, long-time smokers, and smokers who started at an early age. This was particularly well assessed prospectively both in the Nurses’ Health Study [1] and the WHI observational study [2]. The biological plausibility of this association is that compounds found in tobacco smoke, such as polycyclic hydrocarbons, aromatic amines and N-nitrosamines, may induce specific DNA adducts and mutations in the p53 gene in the breast tissue of smokers and so promote breast cancer. 
 
The rationale for the different risks of breast cancer associated with smoking according to age, menopause status and age at first pregnancy is the following: heavy smoking at a young age, before the differentiation stage, can promote mutations and act as a carcinogen. After menopause, smoking could develop its anti-estrogenic effect in women with low levels of estrogens (no postmenopausal hormone use). This effect could be insufficient in premenopausal women or in women under hormone therapy. The association with lobular cancers in the paper by Luo and colleagues [2] is not clearly explained by this hypothesis. It remains the only study to show such an association. Since the levels of all these relative risks remain low, direct causality remains to be demonstrated and potential confounding factors associated with smoking may persist. These two studies are, however, concordant in the finding of a very small increase of the relative risk of breast cancer during heavy active or passive smoking.

Comentario

Anne Gompel
Unité de Gynécologie-Endocrinienne, APHP, Hôtel-Dieu Hospital and University Paris Descartes, France

    References

  1. Xue F, Willett WC, Rosner BA, Hankinson SE, Michels KB. Cigarette smoking and the incidence of breast cancer. Arch Intern Med 2011;171:125-33.
    http://www.ncbi.nlm.nih.gov/pubmed/21263102

  2. Luo J, Margolis KL, Wactawski-Wende J, et al. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study. BMJ 2011;342:d1016
    http://www.ncbi.nlm.nih.gov/pubmed/21363864