Is there a link between estrogen and lung cancer? We know there are many differences between lung cancer in women and lung cancer in men. We also know that lung cancer cells have estrogen receptors, that is, areas on the surface of the cell that can bind with estrogen. Though our knowledge is far from complete at this time, what might this mean for women with lung cancer today, or at risk for lung cancer in the future?
Before talking about the studies, it is helpful to explain why some of the results may be very confusing. There are probably several different ways (mechanisms) by which estrogen plays a role in lung cancer. It is also important to point out that many of these studies are talking about two very separate issues. One is causation -- might a higher or lower level of estrogen have an effect on whether someone will develop lung cancer in the first place? The other is progression -– could estrogen cause a lung cancer that is already present to grow faster or slower?
Reproductive History and Lung CancerThough we understand that breast cancer is more common in women who begin having periods at a younger age, studies have not found this to be the case with lung cancer. Lung cancer was thought to be somewhat less common in women who have had more children than in those who have had fewer children or none at all, especially in women who have never smoked. An recent evaluation of studies to date suggests that non-small cell lung cancer, but not small cell lung cancer, may be slightly less common in women who have had more children. One study found that, in contrast to breast cancer, lung cancer risk was slightly lower when women gave birth at a later age. (In comparison, with breast cancer the risk is reduced by having a first child early in life (before 30) but lung cancer risk is slightly reduced by having a last child later in life.)
A recent study suggests that women who have both of their ovaries removed (“surgical menopause”) may have an elevated risk of developing lung cancer. Some studies have also shown a small correlation between early menopause and the development of lung cancer.
Estrogen and Lung Cancer – Animal StudiesOne study on mice suggested that estrogen may promote the growth of lung cancers. In that study, female mice that had ovaries developed more lung tumors than female mice that had their ovaries removed. In addition, when the mice without ovaries were treated with estrogen, their tumors grew faster than mice that weren’t treated with estrogen.
Hormone Replacement Therapy and Lung CancerCombination hormone replacement therapy, or HRT (estrogen and progesterone) for menopausal symptoms may increase the risk of dying from lung cancer, especially in people who smoke. In a study of 16,000 women with non-small cell lung cancer, those who were using combination hormone replacement therapy were 60% more likely to die from the disease. It’s important to note that in this study, combination HRT increased the risk of death from lung cancer if they already had it, but not the chance that someone would develop lung cancer.
In contrast to women on combination HRT, women who use estrogen replacement alone (unopposed estrogen) do not appear to have an increase in the incidence or mortality from lung cancer.
Studies looking at combination HRT as a cause of lung cancer have been mixed, with some showing an increase, some showing no association, and some newer studies actually showing a decrease in lung cancer risk. One study also found a lower risk of lung cancer among women who had used oral contraceptive pills.
Phytoestrogens and Lung CancerThe intake of plant-based estrogens (phytoestrogens), such as those found in soy, have been looked at in a few studies with lung cancer. In some of these, it appeared that women who consume a diet higher in phytoestrogens have a lower incidence of lung cancer, especially among women who have never smoked.
Bottom Line on Estrogen and Lung CancerSince lung cancer is, in many ways, a different disease in women, it is important to look at the possible role of estrogen. But as noted above, what we understand about estrogen and lung cancer is still in the early stages.
With any procedure or medication, it is extremely important to weigh the benefits of treatment against the possible risks. For example, if your doctor recommends that you have your ovaries removed for some reason, the benefit of the procedure may far outweigh a possible increase in lung cancer risk.
For now, these studies are a good reminder to talk with your doctor if you are on hormone replacement therapy, particularly if you smoke, and to ask questions. Do you need to take the medications? Are there any alternatives? Are there benefits that go beyond the potential risk of a higher mortality from lung cancer (or breast cancer)?
On a last note, understanding that lung cancer cells have estrogen receptors opens doors that perhaps some of the medications used traditionally for breast cancer, could have a role in the treatment of lung cancer in the future.
Chlebowski, R. et al. Lung Cancer Among Postmenopausal Women Treated With Estrogen Alone in the Women’s Health Initiative Randomized Trial. Journal of the National Cancer Institute. 2010 Aug 13 (Epub ahead of print)
Chlebowski, R. et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of randomized controlled trial. Lancet. 2009. 374(9697):1243-51.
Dahabreh, I. et al. Parity and risk of lung cancer in women: Systematic review and meta-analysis of epidemiological studies. Lung Cancer. doi: 10.1016/j.lungcan.2011.10.014. Published online December 12, 2011.
Hammoud, Z. et al. Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma. Endocrine-Related Cancer. 2008. 15(2):475-83.
Koushik, A. et al. Characteristics of menstruation and pregnancy and the risk of lung cancer in women. International Journal of Cancer. 2009. 125(10):2428-33.
Meinhold, C. et al. Reproductive and hormonal factors and the risk of nonsmall cell lung cancer. International Journal of Cancer. 2011. 128(6):1404-13.
Pesatori, A. et al. Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO). British Journal of Cancer. 2013 Sep 3. (Epub ahead of print)>
Pesatori, A. et al. Reproductive and hormonal factors and risk of lung cancer: The EAGLE Study. International Journal of Cancer. 2012 Nov 6. (Epub ahead of print)
Rodriquez, C. et al. Postmenopausal hormone therapy and lung cancer risk in the cancer prevention study II nutrition cohort. Cancer Epidemiology Biomarkers and Prevention. 2008. 17(3):655-60.
Seow, A. et al. Reproductive variables, soy intake, and lung cancer risk among nonsmoking women in the Singapore Chinese Health Study. Cancer Epidemiology Biomarkers and Prevention. 2009. 18(3):821-7.
Shimazu, T. et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. American Journal of Clinical Nutrition. 2010. 91(3):722-8.
Siegfried, J. Early changes in pulmonary gene expression following tobacco exposure shed light on the role of estrogen metabolism in lung carcinogenesis. Cancer Prevention Research (Philadelphia, Pa). 2010. 3(6):692-5.
Slatore, C. et al. Lung cancer and hormone replacement therapy: association in the vitamins and lifestyle study. Journal of Clinical Oncology. 2010. 28(9):1540-6.
Yao, Y. et al. Hormone replacement therapy in females can decrease the risk of lung cancer: a meta-analysis. PLoS One. 2013. 14(8):e71236.