ORLANDO — Hormone therapy with estrogen plus progestin for more than 5 years increased the risk of death in women diagnosed with non-small cell lung cancer, based on secondary analyses from the Women's Health Initiative reported at the annual meeting of the American Society of Clinical Oncology.
The increased risk was most notable in women who were current smokers. One in 100 current smokers using combined hormone therapy (HT) in the trial experienced an avoidable death from non-small cell lung cancer during the 8 years of this study, said Dr. Rowan Chlebowski, a medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the study's lead author.
The findings “should influence discussions between physicians and women considering hormone therapy use, especially for those with a smoking history,” Dr. Chlebowski said. Women who smoke and are seeking or already receiving hormone therapy should be strongly advised to quit smoking.
The Women's Health Initiative (WHI) was a randomized, placebo-controlled clinical trial that examined the health effects of continued use of conjugated equine estrogen plus medroxyprogesterone in 16,608 mostly healthy postmenopausal women. In current practice, HT is recommended for brief use in the treatment of menopausal symptoms, offers alternative hormone sources, and is given at doses that are about half of those used in the WHI. The WHI was launched in 1993; the estrogen-progestin arm of the WHI was stopped in 2002.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in women. Previous research indicates that hormones play a role in NSCLC, but this is the first study to examine a specific correlation in a randomized, double-blind design and with a large, ethnically diverse population. A limitation of this study was the secondary nature of the analyses. The findings on the risk and outcome of lung cancer were not a primary objective of the WHI.
NSCLC incidence and mortality were examined during the 5.6 years of intervention with HT or placebo and 2.4 additional years of follow-up.
While the incidence of NSCLC diagnosis was not significantly different for controls and women on HT, survival after diagnosis was significantly lower in the hormone therapy group. There were 67 deaths among 96 women on HT and 39 deaths in 72 cases in the control group. Further, median survival was 9.4 months in the HT group and 16.1 months in the control group.
The HT and control groups were evenly matched for smoking history with 50% never smokers, 40% former smokers, and 10% current smokers. But when the data on NSCLC deaths were analyzed by tobacco use, the risk was higher in current smokers and considerably higher in smokers also taking HT.
Of the 67 NSCLC deaths in the hormone therapy group, 27 occurred in 800 current smokers. The other 38 deaths occurred in 9 of 4,178 never smokers and in 29 of 3,362 former smokers. Of the 39 NSCLC deaths in the control group, 19 occurred in 838 current smokers. The other 20 deaths occurred in 5 of 3,999 never smokers and in 15 of 3,157 past smokers.
The nature of HT has changed since the WHI, with most women on lower-dose therapies for shorter periods of time, Dr. Chlebowski acknowledged in an interview.
Dr. Chlebowski disclosed that he is a consultant and adviser to many pharmaceutical companies. These disclosures were not relevant to the WHI analysis.
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Women who smoke and are seeking or already receiving HT should be strongly advised to quit smoking. DR. CHLEBOWSKI