March 9, 2015

Stanton A. Glantz, PhD

Yet another high quality study finds that smoking causes breast cancer, especially in younger women before they have kids

Chelsea Catsburg, Anthony Miller, and Thomas Rohan from the Albert Einstein College of Medicine and the University of Toronto recently published “Active cigarette smoking and risk of breast cancer,” a large, long-term and very well done longitudinal study of 89,835 women followed forward in time for a mean of 22.1 years.  They found:

  • Smoking is associated with increased breast cancer
  • There is a dose-response;  women who smoke longer, more cigarettes per day, and who have higher cumulative exposure (pack years) are at higher risk
  • The younger women are when they start smoking,  the higher the risk
  • Smoking before first pregnancy is especially dangerous; number of years smoked prior to first full-term pregnancy was associated with higher risk of breast cancer than comparative years smoked post-pregnancy (among women who have had babies)

The authors’ bottom line:  “These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.”
As the authors note in their paper, their research has many important strengths:  “Strengths of this study were the sample size and extended follow-up time, resulting in a large number of breast cancer cases, the prospective design, which limits the effects of recall bias, and the detailed information  ollected on both the exposure and potential confounders.” 
The Introduction to the paper outlines the underlying biology that explains why smoking should cause breast cancer:

Cigarette smoking has numerous well documented systemic effects and mammary tissue is capable of uptake of many of the tobacco carcinogens routinely found in the circulation of smokers, including polycyclic aromatic hydrocarbons, aromatic amines and N-nitrosamines.   Mammary epithelial cells can subsequently metabolize and activate these compounds into electrophilic intermediates capable of DNA damage and adduct formation.  Smokers have a higher prevalence of these tobacco-related DNA adducts than nonsmokers, and genomic alterations of mammary epithelial cells exposed to tobacco carcinogens resemble those seen in familial breast cancer.  Moreover, tobacco use increases the frequency of p53 gene mutations in breast tumors to levels consistent with those found in lung cancer.

The authors specifically addressed one of the reasons that the CDC in its Surgeon General  Reports has continued to discount the evidence linking smoking and breast cancer:

We saw no evidence of effect modification of any of the smoking variables by randomization group. A concern of the most recent [2014] US Surgeon General Report is that breast cancer screening behavior may influence the perceived association between active smoking and risk of breast cancer, given evidence that smokers have a much lower rate of screening than non-smokers.  Our results suggest that annual mammography screening does not modify the association between smoking and breast cancer risk.

They also recognize that the fact that they compared women who smoked to all nonsmoking women, which includes a lot of passive smokers

A further important limitation of our study was that we did not have data on environmental tobacco exposure and thus we were unable to assess this association, or exclude those who were exposed to environmental tobacco smoke from the reference group. If breast cancer risk is elevated in those with environmental tobacco exposure, inclusion of women with this exposure in the reference group would have attenuated the associations.

This is very important, because both the 2005 California Environmental Protection Agency and 2006 Surgeon General’s report found increased risk of breast cancer in younger women exposed to secondhand smoke of around 1.6.  (comparison). Accounting for the fact that most women in this study (especially a long time ago before they had babies) were likely exposed to secondhand smoke would mean that comparing breast cancer risk on smokers with non-passively exposed nonsmoking women would yield a risk of nearly 2 (1.2 x 1.6), i.e., a doubling of risk of breast cancer among active smokers.

This study, combined with the recent study from the American Cancer Society, Harvard, and National Cancer Institute, which found essentially the same thing, should provide more than enough evidence for the CDC and Surgeon General to (finally) realize that the conclusion they reached in the 2006 Surgeon General Report that “the evidence that active smoking causes no overall increase in breast cancer risks” is wrong and start warning women that smoking and passive smoking cause breast cancer.
The study, published in the International Journal of Cancer is available here.

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