Hormone therapy in postmenopausal women increases the risk of death from lung cancer, according to a newly published post hoc analysis of the large and influential placebo-controlled Women's Health Initiative trial.
Lung cancer incidence was not higher in women who were treated with estrogen plus progesterone, but they were significantly more likely to die of the disease, the investigators reported. The mortality effect was most pronounced in smokers and former smokers. No difference was seen in mortality from small cell lung cancer.
“Our findings should be considered before the initiation or continuation of combined hormone therapy in postmenopausal women, especially those with a high risk of lung cancer, such as current smokers or long-term past smokers,” concluded the investigators, led by Dr. Rowan T. Chlebowski of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif. (Lancet 2009 Sept. 19 [doi:10.1016/S0140-6736(09)61526-9
In an accompanying comment, Dr. Apar Kishor Ganti of the University of Nebraska Medical Center in Omaha said that hormone therapy (HT) should probably be avoided in women at high risk for lung cancer—and maybe should not be used at all (Lancet 2009 Sept. 19 [doi:10.1016/S0140-6736(09)61571-3
“These results, along with the findings showing no protection against coronary heart disease, seriously question whether [hormone therapy] has any role in medicine today. It is difficult to presume that the benefits of routine use of such therapy for menopausal symptoms outweigh the increased risks of mortality, especially in the absence of improvement in the quality of life,” wrote Dr. Ganti.
The Women's Health Initiative trial randomized 16,608 mostly healthy postmenopausal women (8,506 to combined hormone therapy and 8,102 to placebo) at 40 centers in the United States from 1993 to 1998.
The trial was halted after an average follow-up of 5.6 years when investigators determined that higher risks of cardiovascular disease, coronary heart disease, stroke, venous thromboembolism, and breast cancer outweighed the benefits from lower risks for fractures and colorectal cancers among women in the combined HT arm.
Lung cancer was not a predefined study outcome, but the investigators became suspicious when deaths from other cancers were not sufficient to explain excess mortality in women treated with HT.
The subsequent intent-to-treat analysis, performed at an average follow-up of 7.9 years, found that more lung cancer occurred in the combined HT arm (109 cases) than in women treated with placebo (85 cases), with non–small cell lung cancer (NSCLC) occurring in 96 and 72 women, respectively, in the two groups.
These differences were not statistically significant, but the curves began to separate after 5 years, with more lung cancer (particularly NSCLC) occurring after that time in women who were given combined HT than in those who had been on placebo.
Among the women who were diagnosed with lung cancer, 78 deaths occurred during follow-up in the combined HT arm vs. 49 in the placebo group, a difference that was statistically significant, with an incidence per year of 0.12% and 0.08%, respectively (hazard ratio, 1.50), the investigators reported.
NSCLC was the cause in 62 of these deaths in the HT arm and in 31 in the placebo group, with an incidence per year of 0.09% vs. 0.05%, respectively (HR, 1.87).
The investigators also reported that an exploratory analysis showed shorter median survival after lung cancer diagnosis in the combined HT population (9.4 months vs. 16.1 months in their control group counterparts), and significantly higher mortality (70% vs. 54%) at 4 years after diagnosis (HR, 1.59).
The Women's Health Initiative was supported by the National Heart, Blood, and Lung Institute of the National Institutes of Health.
Dr. Chlebowski disclosed advisory and consulting relationships with various drug companies. Dr. Ganti declared no conflicts of interest. Dr. Chlebowski presented results from this study at the annual meeting of the American Society of Clinical Oncology earlier this year.
To see a video interview, go to www.youtube.com/user/ClinicalEndoNews
Lung cancer incidence was not higher in HT-treated women, but they were significantly more likely to die of it.
Source DR. CHLEBOWSKI