High Death Rate from NSCLC in Postmenopausal Women Who Smoke and Use Combination Hormonal Therapy

In the past several years, enough studies have identified negative consequences associated with hormonal therapy in postmenopausal women that what was once standard therapy is becoming ancient practice. Rowan T. Chlebowski, MD, PhD, and colleagues from Harbor-UCLA Medical Center in Los Angeles, California, have added another reason not to treat menopausal symptoms with a combination of estrogen and progestin: it increases the risk of death from non-small cell lung cancer (NSCLC). Dr. Chlebowski said, “Women [already] have an 87% of dying of NSCLC, which is the leading cause of cancer death in women.”

The researchers conducted a retrospective analysis of data from the Women’s Health Initiative, a placebo-controlled trial that enrolled 16,608 postmenopausal women of various ethnic backgrounds to receive conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) or placebo daily for 5.6 years. The health of the women was tracked for a median of 2.4 years after completion of the trial period. The incidences of small cell lung cancer and death due to the disease were similar between the 2 patient groups.

There was an increase in the number of NSCLC cases diagnosed in the treatment group compared with the placebo group, but this was not significant (96 vs. 72, respectively; P = .12). The number of deaths due to NSCLC was significantly higher among the women who had undergone hormonal treatment than for those in the placebo group, however, at 46.3% vs. 27.0%, respectively (hazard ratio, 1.59; 95% confidence interval, 1.03-2.46; P = .04). Researchers also observed an increased trend of mortality due to any cause in the CEE plus MPA group at 3 years post-treatment.

Smoking is commonly associated with an increased risk of lung cancer, and Dr. Chlebowski said his group stratified patients according to smoking status. “Smoking was completely balanced between the 2 groups,” he said. “Fifty percent were nonsmokers, 50% were past smokers, and 10% were current smokers at the time the study started,” he added. As expected, current smokers had a higher cumulative risk of lung cancer in both groups. Even more concerning was the increased rate of death due to NSCLC in current smokers in the hormonal therapy group. These patients had a 3.4% increased risk of death over the entire 7.9-year study period versus 2.3% for smokers in the placebo group. “About 1 out of 100 women who were current smokers who entered the trial had an otherwise avoidable death from NSCLC,“ Dr. Chlebowski said. Comparatively, women who never smoked but received hormonal therapy had a .2% risk of death due to NSCLC; this rate dropped to .1% in the placebo arm.

The researchers said their findings should prompt the medical community to reconsider risks versus benefits of combined hormonal therapy for symptoms of menopause. “Current smokers using combined menopausal hormone therapy should discontinue tobacco use,” he said. Dr. Chlebowski also recommended they consider the increased risk of death should they develop NSCLC before starting a combined hormonal therapy regimen.