Active Smoking and Breast Cancer Risk: Original Cohort Data and Meta-Analysis

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Abstract

The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response. 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. 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. 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.

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The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK

Kirstin Pirie, Richard Peto, Gillian K Reeves … (2013)

Summary Background Women born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life. Hence, only in the 21st century can we observe directly the full effects of prolonged smoking, and of prolonged cessation, on mortality among women in the UK. Methods For this prospective study, 1·3 million UK women were recruited in 1996–2001 and resurveyed postally about 3 and 8 years later. All were followed to Jan 1, 2011, through national mortality records (mean 12 woman-years, SD 2). Participants were asked at entry whether they were current or ex-smokers, and how many cigarettes they currently smoked. Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking. We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers. Findings After excluding 0·1 million women with previous disease, 1·2 million women remained, with median birth year 1943 (IQR 1938–46) and age 55 years (IQR 52–60). Overall, 6% (66 489/1 180 652) died, at mean age 65 years (SD 6). At baseline, 20% (232 461) were current smokers, 28% (328 417) were ex-smokers, and 52% (619 774) were never-smokers. For 12-year mortality, those smoking at baseline had a mortality rate ratio of 2·76 (95% CI 2·71–2·81) compared with never-smokers, even though 44% (37 240/85 256) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking. Mortality was tripled, largely irrespective of age, in those still smoking at the 3-year resurvey (rate ratio 2·97, 2·88–3·07). Even for women smoking fewer than ten cigarettes per day at baseline, 12-year mortality was doubled (rate ratio 1·98, 1·91–2·04). Of the 30 most common causes of death, 23 were increased significantly in smokers; for lung cancer, the rate ratio was 21·4 (19·7–23·2). The excess mortality among smokers (in comparison with never-smokers) was mainly from diseases that, like lung cancer, can be caused by smoking. Among ex-smokers who had stopped permanently at ages 25–34 years or at ages 35–44 years, the respective relative risks were 1·05 (95% CI 1·00–1·11) and 1·20 (1·14–1·26) for all-cause mortality and 1·84 (1·45–2·34) and 3·34 (2·76–4·03) for lung cancer mortality. Thus, although some excess mortality remains among these long-term ex-smokers, it is only 3% and 10% of the excess mortality among continuing smokers. If combined with 2010 UK national death rates, tripled mortality rates among smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference. Interpretation Among UK women, two-thirds of all deaths of smokers in their 50s, 60s, and 70s are caused by smoking; smokers lose at least 10 years of lifespan. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater. Stopping before age 40 years (and preferably well before age 40 years) avoids more than 90% of the excess mortality caused by continuing smoking; stopping before age 30 years avoids more than 97% of it. Funding Cancer Research UK, Medical Research Council.