Table 1 shows the baseline characteristics of the study subjects by disease status. Women who developed invasive breast cancer were slightly older than women who did not, but their body mass index and physical activity were similar. Compared with women who remained free of breast cancer, those who developed the disease were significantly more likely to be non-Hispanic white, more highly educated, nulliparous, older at first live birth, and to have a history of taking oestrogen plus progesterone hormone therapy, heavier alcohol intake, and a family history of breast cancer (all P values <0.05). Women who developed breast cancer were also less likely to have never smoked that those who did not develop cancer (48.1% v 51.4%). Among lifetime non-smokers, 88.1% were exposed to passive smoking, and most women had multiple types of passive smoking exposure. Childhood exposure only was slightly higher among the non-smokers who developed breast cancer than those who did not, as was multiple types of passive smoking exposure (table 1).
Table 1 Baseline characteristics of 79 990 postmenopausal women by diagnosis of invasive breast cancer (values are numbers (percentages) of women unless stated otherwise)
Among women who had never smoked, we did not observe a significant association between breast cancer risk and passive smoking except for the highest level of exposure (childhood exposure ≥10 years, adult home exposure ≥20 years, and adult work exposure ≥10 years) (table 2). We also did not observe a significant dose-response trend for any method of estimating cumulative exposure, with all the estimates being qualitatively similar to the categorical results shown in table 2. In the women who had never smoked with the most extensive exposure to passive smoking, we observed a 32% (95% confidence interval 4% to 67%) excess risk of breast cancer (table 2).
Table 2 Cases of incident invasive breast cancer and related hazard ratios associated with exposure to passive smoking among 41 022 postmenopausal women who had never smoked
We assessed the risk of breast cancer associated with different measures of active smoking by including or excluding passive smokers in the reference category who had never smoked (table 3). In the primary analysis, with all lifetime non-smokers as the reference group, breast cancer risk was elevated by 9% (2% to 17%) among former smokers and by 16% (0% to 34%, P=0.05) among current smokers. Compared with never smoking, the risk of breast cancer was positively associated with smoking intensity, smoking duration, and pack years of cigarette smoking, and inversely associated with age at smoking initiation. Compared with never smokers who had at least one full term pregnancy, women who began smoking before their first full term pregnancy had a 21% (11% to 33%) elevated risk of breast cancer. All trend tests were statistically significant. The highest breast cancer risk was found among women who had smoked for ≥50 years (hazard ratio 1.35 (1.03 to 1.77)). Among former smokers, the years since quitting smoking was significantly inversely associated with breast cancer risk. An increased risk of breast cancer persisted for up to 20 years after smoking cessation.
Table 3 Cases of incident invasive breast cancer and related hazard ratios associated with smoking status among 79 990 postmenopausal women
Since extensive exposure to passive smoking was associated with increased breast cancer risk, which could result in underestimating the risks of active smoking, we conducted a secondary analysis using lifetime non-smokers with no history of any exposure to passive smoke as the reference group. In general, the point estimates of active smoking risks in this secondary analysis were higher than those based on inclusion of passive smokers in the reference group but were less precise because of the much smaller size of the reference group. The hazard ratio for breast cancer among current smokers was significantly elevated (P<0.05) regardless of the reference group used, as was the risk among women who started smoking before their first term pregnancy, smoked for ≥50 years, or had ≥50 pack years of smoking (table 3).
Finally, we assessed the association between smoking exposure and the risk of breast cancer for different types of breast cancer (table 4). There was no significant association of extensive passive smoking with any breast cancer type, but statistical power was limited by the small sample sizes. There was a non-significant trend towards a stronger association of current smoking with lobular cancer than with ductal cancer (P for interaction=0.13). Although there was a significant association of former and current smoking with tumours that were hormone receptor positive (for both oestrogen and progesterone, the dominant subtype), statistical power was probably too limited to assess whether this was true with other hormone receptor subtypes (P for interaction >0.2) (table 4). When we examined the associations of the different variables of active smoking (including age of smoking initiation, intensity, duration, and pack years of smoking) on the risk of breast cancer for these subgroups, we found similar patterns to that of breast cancer overall for dominant subtypes (ductal cancer and hormone receptor positive) and no clear pattern for other subtypes (data not shown).
Table 4 Cases of incident invasive breast cancer and related hazard ratios among 79 990 postmenopausal women by cancer subtypes and exposure to tobacco smoke