Smoking Early in Life Is More Strongly Associated with Increased Risk of Breast Cancer 


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Analyses of data from 73,388 women in the American Cancer Society’s Cancer Prevention Study II (CPS-II) Nutrition Cohort and from a meta-analysis including 14 other studies “support the hypothesis that active smoking increases the risk of breast cancer, especially when smoking begins at an early age.” While the potential confounding effect of alcohol use—a known risk factor for breast cancer—has been a persistent question in studies of the relationship between smoking and breast cancer, in the CPS-II cohort, alcohol consumption “did not appreciably confound these associations.” 

The CPS-II analyses were based on 3,721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. At the time of enrollment in the study, 8.2% of women reported current smoking, 35.6% reported former smoking, and 56.2% reported never smoking. 

“In multivariable-adjusted models with smoking status as a time dependent variable, breast cancer 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,” the researchers reported in the Journal of the National Cancer Institute. Women who started smoking before menarche or after menarche but 11 or more years before giving birth to their first child had higher risk (Ptrend = .03). 

“In analyses that stratified an alcohol drinking status, breast cancer was associated with current smoking ... in women who reported current and former drinking, but not in women who reported never drinking. However, the test for interaction between smoking and alcohol consumption was not statistically significant (P = .11),” the investigators noted. 

The meta-analyses were based on 31,198 breast cancer case patients in 15 cohorts totaling 991,100 women. Current and former smoking were weakly associated with breast cancer risk, but “younger age at smoking initiation was associated with a 12% increase in breast cancer risk,” researchers reported.

“The most consistent evidence supporting a causal relationship between cigarette smoking and breast cancer risk is the stronger association observed for women who initiate smoking before age at first birth,” the authors pointed out. “Mammary tissue is thought to be more susceptible to genotoxic exposures before completion of the first full-term pregnancy because the terminal ductal–lobular units of the breast are not fully differentiated until the end of gestation. The relationship with early life smoking that we and others observed, together with the lack of a consistent relationship between breast cancer risk and smoking later in life, suggests that active cigarette smoking may play a greater role in the initiation than the progression of breast cancer.” ■

Gaudet MM, et al: J Natl Cancer Inst 105:515-525, 2013.



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