One of my areas of interest is studying gender-related differences in lung cancer. Earlier this year, I wrote a post about interesting data that had come out of the Women’s Health Initiative study. This was the landmark study that established that hormone replacement therapy (HRT) for postmenopausal women did more harm than good. When originally presented in 2002, the investigators noted significantly increased risks of breast cancer, cardiovascular disease and stroke. At ASCO 2009, they also reported an increase in lung cancer incidence and lung cancer mortality among postemenopausal women who received HRT compared to those who received placebo.

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This data got some researchers in Switzerland thinking. If estrogens increased the risk of lung cancer, would anti-estrogens decrease the risk of lung cancer? Who is taking anti-estrogens? Women with breast cancer. So the researchers studied almost 7,000 breast cancer patients in the Geneva Cancer Registry. About half of these women took tamoxifen, an anti-estrogen used to decrease the risk of breast cancer relapse and also for breast cancer prevention. Findings from the study were recently presented at the annual San Antonio Breast Cancer Symposium. The investigators identified a strong trend towards decreased incidence of lung cancer in breast cancer survivors on tamoxifen (p = .058) and a significant decrease in the risk of death from lung cancer among women taking tamoxifen (p < .0001). The authors compared incidence of lung cancer and death from lung cancer among the two groups of breast cancer survivors. They also compared the findings in each group to expected lung cancer incidence and death in an age-matched population without breast cancer. Not only did the breast cancer patients on tamoxifen experience lower lung cancer mortality than the other breast cancer patients, their rates were lower than would be expected in a healthy population.

Although there was a trend towards lower lung cancer incidence, tamoxifen appeared to have a bigger impact on mortality from lung cancer. This suggests that even with a diagnosis of lung cancer, tamoxifen may have an effect on the biology of the cancer such that fewer women died of their disease.

This line of thinking is not new. We have known for some time that normal lung tissue and lung cancer cells express estrogen receptors and thus have the potential to be affected by estrogen, which can actually be produced in the lung. While women as a whole have a better prognosis compared to men, premenopausal women do not seem to have the same favorable prognosis. Higher blood estrogen levels have been associated with worse outcomes in men and women compared to those with lower levels and animal studies have shown that anti-estrogens can shrink lung tumors.

Patients have asked me if they should stop taking their HRT after a diagnosis of lung cancer and I have generally encouraged this. But I still can’t answer the question of whether anti-estrogens will be helpful in the treatment of lung cancer. This study, though intriguing, was retrospective and we don’t know whether there was a confounding factor that accounted for the benefit in terms of lung cancer mortality in women on tamoxifen. For example, could women have been taking another medication for tamoxifen side effects (notorious hot flashes) that might have been the real driving factor behind the benefit seen? There are some clinical trials which will be looking more closely at anti-estrogen therapy in lung cancer patients. Until then, though, I don’t feel that hypothesis-generating data we have justifies the use of anti-estrogens, particularly given substantial side effects.

In addition to estrogen’s direct effect on lung cancer cells, we have laboratory studies which suggests interactions between the estrogen receptor and other pathways involved in lung cancer progression, such as EGFR. Tarceva is currently being studied in combination with a different anti-estrogen (Faslodex) and I anticipate other studies in this vein.

If you are interested, more references and information on lung cancer in women can be found in a presentation I recently gave for patients, available here:

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