Cigarette smoking is an established cause of a variety of
cancer types, but its role in
breast cancer etiology is not clear. In this report, the potential role of cigarette
smoke carcinogens as causes of human
breast cancer is evaluated. Of over 60 known
carcinogens in tobacco
smoke, several are known to induce mammary
tumors in laboratory animals:
benzo[a]pyrene (B[a]P),
dibenzo[a,l]pyrene (DB[a,l]P),
2-toluidine,
4-aminobiphenyl, 2-amino-3-methylimidazo[4,5-f]
quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP),
1,3-butadiene,
isoprene,
nitromethane,
ethylene oxide, and
benzene. Studies in humans demonstrate that tobacco constituents can reach breast tissue. The uptake and metabolic activation of mammary
carcinogens such as
polycyclic aromatic hydrocarbons (PAHs) and
4-aminobiphenyl are frequently higher in smokers than in nonsmokers. Although it is likely that specific mammary
carcinogens in tobacco
smoke can reach breast tissue, evidence is lacking at the present time. Some PAHs present in cigarette
smoke can be metabolized to sterically hindered diol
epoxides, which are potent mammary
carcinogens. Thus, compounds such as
benzo[c]phenanthrene (B[c]P), not classically considered to be a strong
carcinogen in rodents, could nevertheless be metabolized in humans to diol
epoxides carcinogenic to the breast. Collectively, the link between smoking and
breast cancer is plausible but has been difficult to establish, probably because of the low
carcinogen dose.