Lung Cancer Mortality Higher in Women Who Used Combination Hormone Therapy

A secondary analysis from the Women's Health Initiative has found that past use of hormone therapy with estrogen plus progestin increases the risk of dying from non–small cell lung cancer for women who develop the disease.

The findings, presented at the 45th Annual Meeting of the American Society of Clinical Oncology in Orlando, Fla, add to growing concerns about the safety of hormone therapy in some women. “These data, together with recent results indicating higher breast cancer risk, suggest cancer impact should influence risk-to-benefit consideration for combined hormone therapy use,” the authors noted.

The Women's Health Initiative is a randomized, placebo-controlled clinical trial evaluating the health effects of conjugated equine estrogen plus medroxyprogesterone acetate in 16 608 postmenopausal women. Previous research has suggested that hormones may play a role in the progression of non–small cell lung cancer because women tend to have higher survival rates than men and they respond better to certain therapies. The Women's Health Initiative is the first study to examine a specific correlation in a randomized clinical trial setting.

This analysis examined the incidence of non–small cell lung cancer and mortality during 5.6 years of intervention with hormone therapy or placebo and 2.4 years of additional follow-up. There was no significant difference in lung cancer incidence between the 2 groups, but mortality after a lung cancer diagnosis was significantly higher in those who received combined hormone therapy. Specifically, women in the hormone therapy group were 61% more likely to die from lung cancer during the follow-up period than were women in the placebo group (67 vs 39 deaths, respectively).

The researchers noted that women who have taken hormone therapy and who are current smokers have a particularly high risk of dying from lung cancer. One in 100 current smokers in the trial who used combined hormone therapy experienced an avoidable death from lung cancer during the 8 years of this study. The mortality rate after diagnosis was 3.4% among smokers in the hormone therapy group compared with 2.3% among smokers in the placebo group over the study period.

“Current smokers using combined hormone therapy should discontinue tobacco use,” said lead author Rowan Chlebowski, MD, PhD, a medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. “Current smokers also should carefully consider this mortality risk before beginning or continuing combined hormone therapy,” he added.

These findings were in contrast to the results of most case-control studies that have not found an increased risk, according to Bruce Johnson, MD, director of the Lung Cancer Program at the Dana-Farber/Harvard Cancer Center, who was not involved in the research. “This [Women's Health Initiative study] is likely more accurate since it is . . . a prospective randomized study,” he said.

These latest findings may encourage additional studies on the effects of hormones on the development and progression of lung cancer. The investigators also hope that their results will prompt physicians and patients to reassess the use of combined hormone therapy for the treatment of menopausal symptoms.