Smoking at time of diagnosis and breast cancer-specific survival: new findings and systematic review with meta-analysis

Abstract

Introduction: In women with breast cancer who smoke, it is unclear whether smoking could impair their survival from the disease.

Methods: We examined the relation of smoking at diagnosis to breast cancer-specific and overall survival among 5,892 women with invasive breast cancer treated in one Canadian center (1987 to 2008). Women were classified as never, former or current smokers. Current smokers were further classified according to total, intensity and duration of smoking. Deaths were identified through linkage to population mortality data. Cox proportional-hazards multivariate models were used. A systematic review with meta-analysis combines new findings with published results.

Results: Compared with never smokers, current smokers at diagnosis had a slightly, but not statistically significant, higher breast cancer-specific mortality (hazard ratio = 1.15, 95% confidence interval (CI): 0.97 to 1.37). Among current smokers, breast cancer-specific mortality increased with total exposure to, intensity and duration of smoking (all Ptrend <0.05). Compared to never smokers, breast cancer-specific mortality was 32 to 56% higher among heavy smokers (more than 30 pack years of smoking, more than 20 cigarettes per day or more than 30 years of smoking). Smoking at diagnosis was associated with an increased all-cause mortality rate. A meta-analysis of all studies showed a statistically significant, 33% increased mortality from breast cancer in women with breast cancer who are smokers at diagnosis compared to never smokers (hazard ratio = 1.33, 95% CI: 1.12 to 1.58).

Conclusions: Available evidence to date indicates that smoking at diagnosis is associated with a reduction of both overall and breast cancer-specific survival. Studies of the effect of smoking cessation after diagnosis on breast cancer-specific outcomes are needed.

Figure 1

Search strategy and study selection process used in the meta-analysis of the association between smoking status and breast cancer-specific mortality.

Figure 2

Forest plot with study specific and random effects for association between smoking status (current versus never) and breast cancer specific-mortality. In two studies, the authors present multivariate adjusted HRs for current smokers from two distinct models (HRs of 1.41 and 1.08 in Table 2 in Fentiman [11] and HRs of 2.14 and 1.95 in Table 1 in Manjer [12]); the present meta-analysis is based on the HR that was adjusted for the most complete set of prognostic factors including age. In the study by Dal Maso et al. [8] results were published separately for cases currently smoking <15 cigarettes/day (HR: 1.39) and those smoking ≥15 cigarettes/day (HR: 1.23), as compared with never smokers; the corresponding HRs among current smokers were weighted in proportion to the numbers in each subgroup (182 and 108, respectively) and then combined. The summary HR and 95% CI are from random-effects models. CI, confidence interval; HR, hazard ratio.

Figure 3

Funnel plot with a triangular 95% confidence region.