Lung Cancer in Women: The Differences in Epidemiology, Biology and Treatment Outcomes

Maria Patricia Rivera


Expert Rev Resp Med. 2009;3(6):627-634. 

In This Article

Hormonal Differences

It has been hypothesized that steroid sex hormones may be a factor in lung carcinogenesis. Estrogen receptor-α (ERα) and -β (ERβ) are expressed in NSCLC (adenocarcinoma and squamous cell carcinoma) cell lines.[41] The exact mechanism by which estrogens may be involved in lung carcinogenesis is not clear, but some investigators have reported that they may act as estrogen receptor ligands and activate cell proliferation, or as direct carcinogens via the formation of DNA adducts.[41,42] Taioli and Wynder have reported that exogenous and endogenous estrogens may play a role in the development of adenocarcinoma.[43] In a case–control study, they showed that early age at menopause (40 years of age or younger) is associated with a reduced risk of adenocarcinoma of the lung. In addition, the authors showed that hormonal replacement therapy (HRT) and its interactions with smoking leads to an increased risk of lung cancer in women (OR: 1.7 and 32.4 in nonsmokers and smokers, respectively). A population-based cohort of 23,244 women prescribed HRT who had complete follow-up for an average of 6.7 years revealed an increased risk (relative risk [RR]: 1.26) of lung cancer, and that most of the excess number of lung cancer cases occurred in women under the age of 60.[44] The authors caution, however, that the higher prevalence of smokers in the cohort than in the background population may be the more likely explanation for the 26% excess of lung cancer in this study. In contrast to the above studies, Schabath et al. found that HRT was associated with a reduced risk of lung cancer in current smokers (OR: 0.59);[45] however, this protective effect of HRT was not seen in former smokers or in never-smokers.[45]

Recent data from the Women's Health Initiative trial revealed that women who had lung cancer and were on combined HRT with estrogen and progestin were at an increased risk of death from lung cancer, in particular deaths from NSCLC, compared with women who were not on combined HRT.[46] In addition, one in 100 current smokers in this study experienced an avoidable NSCLC death with combined HRT over the 8-year study period.[46]


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