Estrogen plus progesterone increased mortality from lung cancer in postmenopausal women

Treatment with estrogen plus progesterone in postmenopausal women did not increase incidence of lung cancer, but it did increase the number of deaths caused by lung cancer — in particular deaths from non–small cell lung cancer, according to a post-hoc analysis of the Women’s Health Initiative trial.

“These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk for lung cancer,” the researchers wrote.

In this intention-to-treat analysis, the researchers used data from treatment and post-intervention follow-up periods of the WHI trial to assess the incidence and mortality rates for all lung cancer, small cell lung cancer and NSCLC in 16,608 postmenopausal women aged 50 to 79 years.

Women were randomly assigned to receive once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (Prempro, Wyeth Ayerst; n=8,506) or placebo (n=8,102).

Data indicated that after a mean 5.6 years of treatment and 2.4 years of additional follow-up, 109 women in the combined hormone therapy group were diagnosed with lung cancer compared with 85 women in the placebo group (P=.16).

Further, 96 women in the combined therapy group had NSCLC vs. 72 women assigned to placebo (P=.12). Seventy-three women died from lung cancer in the combined hormone therapy group compared with 40 women in the placebo group (P=.01). In particular, 62 women in the combined hormone therapy group died from NSCLC compared with 31 in the placebo group (P=.004).

“Our findings should be considered before the initiation or continuation of combined hormone therapy in postmenopausal women, especially those with a high risk for lung cancer, such as current smokers or long-term past smokers,” the researchers concluded.

In an accompanying editorial, Apar Ganti, MD, of the University of Nebraska Medical Center in Omaha, Neb., wrote: “In a nutshell, combined estrogen and progesterone therapy increases mortality after a diagnosis of lung cancer … These results show that the incidence curves for the two groups start separating from about five years after randomization. The mean follow-up of 2.4 years might not have been enough for the differences to reach statistical significance.”

Chlebowski RT. Lancet. 2009;doi:10.1016/S0140-6736(09)61526-9.