Tobacco Smoke and Breast Cancer: Whatever Happened to the Precautionary Principle? Stanton Glantz, PhD Professor of Medicine UCSF

New CalEPA report

SHS and breast cancer Causal in younger, primarily premenopausal women 1.7 risk Biggest risk associated with SHS Inconclusive in older women Breast cancer establishment choking on this conclusion Epidemiologists Advocacy groups

Mammary Carcinogens in Tobacco Smoke Aromatic hydrocarbons Benzene Benzo[a]pyrene Dibenz[a,h]anthracene Dibenzo[a,e]pyrene Dibenzo[a,h]pyrene Dibenzo[a,I]pyrene Dibenzo[a,l]pyrene Nitrosamines N-nitrosodiethylamine N-Nitrosodi-n-butyl-amine Aliphatic compounds Acrylamide Acrylonitrile 1,3-Butadiene Isoprene Nitromethane Propylene oxide Urethane Vinyl chloride Arylamines and nitrarenes 4-Aminobiphenyl Nitrobenzene Ortho-Toluidine

Biology These carcinogens can be activated into electrophilic intermediates by enzymes active in the human breast epithelial cell. These metabolites bind to DNA and form DNA adducts that have been detected in human breast epithelium

Biology (contd) Genes coding for activation and detoxification enzymes (e.g. NAT2, NAT1, CYP1a1, COMT, BRCA1 And BRCA2) modify the relationship of tobacco smoke to breast cancer risk (although results are inconsistent) Genomic alterations observed in vitro after exposure of human breast epithelial cells to tobacco carcinogens resemble those in familial breast cancer. p53 damage in some breast tumors of smokers, but not nonsmokers

SHS Breast Cancer Risk

CalEPA and Surgeon General found similar passive risks California EPASurgeon General ExposurenRelative Risk (95% CI) N All studies ( ) ( ) Premenopausal/ Women < ( ) ( ) Premenopausal with lifetime exposure assessment ( )61.85 ( )

Surgeon General’s Basic Premise “ There is substantial evidence that active smoking is not associated with an increased risk of breast cancer in studies that compare active smokers with persons who have never smoked.” Surgeon General’s Report 2006 (p 446)

Surgeon General Relies Heavily on 53 Study Collaborative Reanalysis “In a pooled analysis of data from 53 studies, the relative risk for women who were current smokers versus life-time non-smokers was 0.99 (95% CI, ) for the 22,225 cases and 40,832 controls who reported not drinking alcohol. The effect of smoking did not vary by menopausal status.” Surgeon General’s Report 2006 (p 446)

Effect of Exposure Misclassification on Estimates of Relative Risk Relative Risk: = 5

Effect of Exposure Misclassification on Estimates of Relative Risk Relative Risk: = 5 = 2

Comparison of breast cancer risk from active and passive smoke exposure in studies CalEPA considered most informative

Utilizing Unexposed Referent Raises Risk Estimate (within study comparison, Morabia et al. 1996) Exposure Smokers vs non- smokers with no ETS Smokers vs non- smokers (includes ETS exposed) Active 1-9 cpd 2.2 (1.0; 4.4) 1.2 (0.8; 2.0) cpd 2.7 (1.4; 5.4) 1.7 (1.1; 2.5) ≥ 20 cpd 4.6 (2.2; 9.7) 1.9 (1.2; 2.9) Ever passive 3.2 (1.7; 5.9) (Similar within study comparison results in Johnson et al., 2000, Lash and Aschengrau, 1999, and Kropp and Chang Claude, 2002)

What about Confounders? (Premenopausal Studies)

Evidence for breast cancer in younger women stronger than lung cancer in 1986 Lung cancer /13 elevated risk 5 significant 1/3 cohort studies significant Hirayama*, Garfinkle,Gillis No toxicology No molecular epi Breast cancer /14 elevated risk 7 significant 1/3 cohort studies significant Hanaoka*, Reynolds, Wartenberg Positive toxicology Molecular epi

Average Secondhand Smoke Levels Average Second Hand Smoke Levels LOW HIGH 1 to 3 2 to 6 3 to 8 10 to 40 Hammond SK. Environmental Health Perspectives 1999; 107(2).

The American Cancer Society … "Mainstream health organizations are intentionally cautious in making claims about tobacco, reserving final judgment until the evidence cannot be dismissed by the tobacco industry."

Implications for Workplace Exposure of Waitresses Highest occupational exposure to SHS: 72.3% These women tend to get exposed at the most vulnerable times 1.7 relative risk 30% of breast cancer in younger waitresses

Sources CalEPA ental_tobacco/2005etsfinal.html ental_tobacco/2005etsfinal.html Chapter 7 of Part B Surgeon General /secondhandsmoke/report/ /secondhandsmoke/report/ Chapter 7