BMC Cancer 2008, 8:157 http://www.biomedcentral.com/1471-2407/8/157 on demographics, reproductive history, family history, exogenous hormone use, alcohol consumption, physical activity, sleeping habits, meat cooking and consumption, and other dietary factors were also included. Statistical methods Categorical variables were compared between cases and controls using the chi-square test or the Mantel-Haenzsel chi-square test for trend. Total years smoked were calcu- lated by summing the lengths of each reported period of smoking. Average cigarettes per day were calculated by weighting the number of cigarettes smoked per day in each period by the number of years in that period, divided by the total number of years. Total pack-years were calcu- lated as the product of total years and average cigarettes per day. Secondhand smoking analyses were restricted to women who smoked less than 100 cigarettes in their lifetime. Total years of secondhand smoke exposure were calcu- lated by summing years across all periods for which women reported residential secondhand smoke exposure. To facilitate comparison with findings from a previous study of detailed secondhand smoke exposure measures [18], a smoker-year was defined for each period of resi- dential secondhand smoke exposure as the product of the number of years in the period and the number of smokers who smoked in the household during that period. Total smoker-years were calculated as the sum of smoker-years across periods. Pack-years were defined as the product of cigarettes smoked per day for a given smoker in a given period and the number of years in that period. Pack-years were summed across smokers for each period and then across periods to generate a total pack-year measure. Weighted pack-years were defined as the product of ciga- rettes smoked per day for each smoker in a given period, the number of hours the woman was exposed to that smoker's smoke each day in that period, and the times the number of years in a period, divided by 18 waking hours in a day. This measure was summed across smokers in each period and across periods to obtain a total weighted pack-years measure. Both years and smoker-years were calculated for all types of tobacco products combined. Average cigarettes per day, pack-years and weighted pack- years were calculated for cigarette exposure only. All sec- ondhand smoke exposure measures were calculated sepa- rately for childhood (exposure prior to age 18) and adulthood and summed to obtain a measure of lifetime secondhand smoking. Associations between tobacco smoke exposure and breast cancer were estimated by using unconditional logistic regression. For initial active smoking analyses, never active smokers (women who never smoked 100 ciga- rettes) were the reference group. For secondhand smoke exposure, never active smokers unexposed to secondhand smoke comprised the reference group. Additional active smoking analyses were conducted, using three more restrictive reference groups based on secondhand expo- sure data; those with: 1) zero years of lifetime residential secondhand smoke exposure and zero years of occupa- tional secondhand smoke exposure; 2) ≤ 10 years of life- time residential secondhand smoke exposure, ≤ 10 years of moderate-level occupational secondhand smoke expo- sure, and ≤ 10 years of heavy-level occupational second- hand smoke exposure; or 3) zero years of residential secondhand smoke exposure before age of 18. Women missing data for any smoker in any period were coded to missing for the corresponding summary variable. Initial regression models included age and menopausal status, given their strong associations with breast cancer. Additional potential confounders were tested individu- ally. If the risk estimate associated with smoking changed by 10 percent in either direction, that variable was included in a full model. If the smoking variables were multilevel, then a factor was included in the final model if it affected 1 out of 2 or 2 out of 3+ levels. Potential con- founders were assessed separately for active and passive tobacco smoke exposure. Separate models were also con- structed for pre- and postmenopausal women. Results Selected characteristics of cases and controls are presented in Table 1. Controls were disproportionately premeno- pausal and college-educated, but similar to cases on other characteristics. Ever-active smoking was associated with a statistically significant increased risk of breast cancer (OR = 1.43, 95% confidence interval (CI) = 1.03–1.99) (Table 2). However, there was no evidence of a dose-response trend in breast cancer risk for total years smoked, average number of cigarettes per day or total pack-years. Ever active smoking prior to the age of 18 was associated with increased risk, but the magnitude of the association was not greater than that for ever smoking overall, and there was no dose response for years smoked prior to age 18. Active smoking before first live birth was not associated with increased risk of breast cancer (Table 2). The risk of breast cancer associated with ever having smoked ciga- rettes was similar for premenopausal women (30 cases, 65 controls; OR = 1.53, 95% CI = 0.60–3.95) and postmeno- pausal women (256 cases, 246 controls; OR = 1.36, 95% CI = 0.95–1.94). Analyses limited to different types of cig- arettes or inhalation levels did not reveal additional asso- ciations (data not shown). Among never active smokers, secondhand smoke expo- sure in the home during childhood was not associated with breast cancer risk, whether exposure was measured in total years, smoker-years, pack-years or weighted pack- Page 3 of 9 (page number not for citation purposes)