Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58 515 women with invasive breast cancer and 95 067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women’s age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 – 1.45, P50.00001) for an intake of 35 – 44 g per day alcohol, and 1.46 (1.33 – 1.61, P50.00001) for 545 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5 – 8.7%; P50.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever smokers and never-smokers (7.1% per 10 g per day, P50.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98 – 1.07, and for current smokers=0.99, 0.92 – 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. Expert Panel on Tobacco Smoke and Breast Cancer Risk 69 Terry, P.D., Rohan, T.E., 2002. Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol. Biomarkers Prev. 11, 953-971. Abstract: Animal experiments and in vitro studies have shown that compounds found in tobacco smoke, such as polycyclic hydrocarbons, aromatic amines, and N-nitrosamines, may induce mammary tumors. The findings of smoking specific DNA adducts and p53 gene mutations in the breast tissue of smokers also support the biological plausibility of a positive association between cigarette smoking and breast cancer, as does the detection of carcinogenic activity in breast fluid. However, epidemiological studies conducted over the past few decades have variably shown positive, inverse, or null associations. To help reconcile the discrepant findings, epidemiologists have paid increasing attention to measures of exposure to tobacco smoke that might be of the greatest etiological importance, to aspects of the smoker that might modify the association between smoking and breast cancer risk, and to the potentially different associations that might exist with different types of breast tumors, such as those with and without estrogen or progesterone receptors. Overall, the results of these studies suggest that smoking probably does not decrease the risk and indeed suggest that there may be an increased breast cancer risk with smoking of long duration, smoking before a first full-term pregnancy, and passive smoking. These findings require confirmation in future studies, as do suggestions of increased risk among women with certain genotypes. Animal experiments and in vitro studies have shown that compounds found in tobacco smoke, such as polycyclic hydrocarbons, aromatic amines, and N-nitrosamines, may induce mammary tumors. The findings of smoking specific DNA adducts and p53 gene mutations in the breast tissue of smokers also support the biological plausibility of a positive association between cigarette smoking and breast cancer, as does the detection of carcinogenic activity in breast fluid. However, epidemiological studies conducted over the past few decades have variably shown positive, inverse, or null associations. To help reconcile the discrepant findings, epidemiologists have paid increasing attention to measures of exposure to tobacco smoke that might be of the greatest etiological importance, to aspects of the smoker that might modify the association between smoking and breast cancer risk, and to the potentially different associations that might exist with different types of breast tumors, such as those with and without estrogen or progesterone receptors. Overall, the results of these studies suggest that smoking probably does not decrease the risk and indeed suggest that there may be an increased breast cancer risk with smoking of long duration, smoking before a first full-term pregnancy, and passive smoking. These findings require confirmation in future studies, as do suggestions of increased risk among women with certain genotypes. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. 2004. Atlanta, GA: U.S. Department of Health and Human Services. Chapter Summary: Since the 2001 Surgeon General’s Report, IARC has concluded that the evidence is indicative of no association between smoking and breast cancer. The weight of epidemiological evidence supports the conclusion that smoking is not associated with breast cancer risk. Subgroups of women cannot yet be reliably identified who are at an increased risk of breast cancer because of smoking, compared with the general population of women. Whether women who are at a very high risk of breast cancer because of mutations in BRCA1 or BRCA2 genes can lower their risks by smoking has not been established. A Meta-RR of 1.03(SE =0.02) of breast cancer in ever smokers vs. never was found when combining cohort and case-control studies. Expert Panel on Tobacco Smoke and Breast Cancer Risk 70 Alberg, A.J., Daudt, A., Huang, H.Y., Hoffman, S.C., Comstock, G.W., Helzlsouer, K.J., Strickland, P.T., Bell, D.A., 2004. N-acetyltransferase 2 (NAT2) genotypes, cigarette smoking, and the risk of breast cancer. Cancer Detect. Prev. 28, 187-193. Discussion: Given the limited size of our current study, and the fact that a non-trivial proportion of participants were missing information concerning pack-years of smoking and exposure to passive smoking, chance remains a viable explanation for our findings that cigarette smoking was not associated with breast cancer risk. It is thus useful to compare the results of this study with eight investigations that examined the association between NAT2 genotypes, smoking, and breast cancer. When the crude results of the nine studies were pooled using the Mantel-Haenzsel odds ration, which is weighted by study size, the OR between ever-versus-never smoking and breast cancer was 1.37 (95% CL 1.19-1.58) among slow acetylators, compared to 1.15 (95% CL 0.97-1.35) among rapid acetylators. Based on the 6 studies that could contribute data, cigarettes smoking was slightly more strongly associated with breast cancer risk among women with NAT2 slow acetylators genotypes if they were current smokers (OR 1.41; 95% CL 1.11-1.79) than former smokers (OR 1.27; 95% CL 1.011.60). Cigarette smoking was most strongly associated with breast cancer risk in postmenopausal women with the NAT2 slow acetylation genotype (OR 1.61; 95% CL 1.292.01), though comparisons were largely limited to ever-versus-never cigarette smokers. The present study together with other epidemiological studies provides at least modest support for the hypothesis that cigarette smoking is associated with an increased breast cancer risk in women with the NAT2 slow acetylator genotype. Lawlor, D.A., Ebrahim, S., Smith, G.D., 2004. Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis. Br. J Cancer 91, 512-518. Abstract: It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60–79 years (N1⁄4139 breast cancer cases), we found no association between smoking before the birth of a first child and breast cancer risk: fully adjusted (for age, number of children, age at birth of first child, age at menarche, age at menopausal, hysterectomy and/or oophorectomy, ever use of oral contraception, use of hormone replacement therapy, alcohol consumption, body mass index, childhood and adulthood social class) odds ratio 1.06 (95% CI: 0.72, 1.56). The pooled estimate from a meta-analysis of our study and 11 previously published studies (N1⁄46528 cases) was 1.07 (0.94, 1.22). We conclude that smoking prior to the birth of a first child is not associated with increased risk of breast cancer. It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60–79 years (N1⁄4139 breast cancer cases), we fo