Background: The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response.
Methods: To investigate these issues further, we analyzed data from 73 388 women in the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort. Analyses were based on 3721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from multivariable-adjusted Cox proportional hazard regression models. P values were two-sided. We also conducted meta-analyses of our results with those published from 14 other cohort studies.
Results: In CPS-II, incidence was higher in current (HR = 1.24, 95% CI = 1.07 to 1.42) and former smokers (HR =1.13, 95% CI = 1.06 to 1.21) than in never smokers. Women who initiated smoking before menarche (HR = 1.61, 95% CI = 1.10 to 2.34) or after menarche but 11 or more years before first birth (HR = 1.45, 95% CI = 1.21 to 1.74) had higher risk (P trend = .03). No relationships were observed with other smoking parameters. Alcohol consumption did not confound associations with smoking status, although neither current nor former smoking were associated with risk among never drinkers (P interaction = .11). In meta-analyses, current (HR = 1.12, 95% CI = 1.08 to 1.16) and former smoking (HR = 1.09, 95% CI = 1.04 to 1.15) were weakly associated with risk; a stronger association (HR = 1.21, 95% CI = 1.14 to 1.28) was observed in women who initiated smoking before first birth.
Conclusions: These results support the hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth and suggest that smoking might play a role in breast cancer initiation.