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New CalEPA report and Breast Cancer

ARB Public Hearing to Decide if TAC Scientific Review Panel Scientific Review Panel Prioritization/Selection Toxic Substance OEHHA Health Evaluation ARB Exposure Assessment Draft Report Public Workshop/ Comments Draft Report Public Workshop/ Comments Toxic Air Contaminants Program Identification

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 Tobacco smoke contains multiple fat- soluble compounds known to induce mammary tumors in rodents. (PAH’s, heterocyclic amines, aromatic amines, and nitro-PAH’s) These carcinogens can be activated into electrophilic intermediates by enzymes active in the human breast epithelial cell.

Biology (contd) Genes coding for activation/detoxification enzymes (e.g. NAT2, NAT1, CYP1a1, COMT, BRCA1 And BRCA2) have been reported to modify the relationship of tobacco smoke to breast cancer risk (although results are inconsistent). Electrophilic metabolites of tobacco compounds bind to DNA and form DNA adducts that can be detected in human breast epithelial Morabia A., Environmental and Molecular Mutagenesis 39:

Biology (contd) 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 Morabia A., Environmental and Molecular Mutagenesis 39:

Problems with exposure assessment

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

SHS Breast Cancer Risk

SHS and Breast Cancer in Younger/Premenopausal Women 14 studies evaluated breast cancer risk in younger/premenopausal women strata. 13/14 found elevated risks ( ), and 7 were statistically significant. Pooled risk estimate from meta-analysis = 1.68 (95% CI ). Pooled risk estimate for studies with lifetime exposure information from all sources = 2.2 (95% CI ) Some evidence of dose-response.

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)

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

Arguments Raised If active smoking does not cause breast cancer, how can passive smoking? Active smoking does cause breast cancer IARC says no effect 2004 report based on meeting in 2001 Considered essentially the same studies as CalEPA 1997 (which did not say SHS caused breast cancer) Only considered 4 studies published between 2000 and 2002 Surgeon General says no effect 2004 report essentially completed in 2001 Considered 5 studies published after 2000 CalEPA considered 23 studies between 2000 and 2005 Cohort studies negative

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

Passive smoking and lung cancer First study, Hirayama 1981 Cohort study in Japan Nonsmoking women married to men who smoked Few women smoked Few women worked outside the home Significant elevation in risk ACS CPS study, Garfinkle Cohort study in USA Nonsignificant elevation in risk Many women smoked and worked outside the home

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

What if you are wrong? Type I (false positive) Women unnecessarily alarmed about passive smoking and breast cancer Tobacco industry attacks Type II (false negative) Young women die of breast cancer Tobacco industry quotes ACS

Where to read the full CalEPA report finalreport/finalreport.htm Passive smoking and breast cancer starts on page 7-76 of Part B Active smoking and breast cancer in Appendix 7A Discussion on exposure missclassification and criteria for causality in Chapter 1 of Part B

What Can You Do? For scientists: Read the report and make your views known For advocates: Use the data. CalEPA has a reputation for being first, ahead of the ACS and CDC, and being right.