Possible HRT Link to Lung Cancer Death

In what may be another nail in the coffin of combination hormone replacement therapy (HRT), researchers said the menopause treatment is linked to an increased risk of dying of lung cancer.

In findings from the landmark Women's Health Initiative, using estrogen and progestin lead to a 59 percent increase in the risk of death if a woman developed non-small cell lung cancer, Dr. Rowan Chlebowski of Harbor-UCLA Medical Center in Los Angeles said at the annual meeting of the American Society of Clinical Oncology.

"This is one of a series of problems, especially with cancer, that work against widespread use of estrogen and progestin," Chlebowski said.

But despite those earlier problems -- increased risk of stroke, blood clots and breast cancer -- many postmenopausal women are use the combined hormone therapy to fight the symptoms of menopause, Chlebowski said.

He said between 25 and 30 million prescriptions are written every year, and 15 percent of postmenopausal women still use the combination.

The Women's Health Initiative study of combined hormone therapy enrolled 16,608 postmenopausal women ages 50 through 79 and randomly assigned them to receive either a dummy placebo treatment or the two hormones.

The study was stopped early when it became obvious that a range of harms from the treatment outweighed the benefits, Chlebowski said.

As the researchers followed the participants, they noticed a significant increase in both fatal and nonfatal cancers among those who got the hormones.

To try to explain the increase, they looked at the effect of the hormones on lung cancer, he said.

Research Shows Possible Link Between HRT, Lung Cancer Death Risk

For small cell lung cancer, there was no difference in incidence or mortality between the arms of the study, Chlebowski said. But for non-small cell lung cancer, analysis showed:

A significant increase in the risk of dying if a woman taking the hormones developed cancer.

Median survival of 9.4 months in women receiving hormones arm, compared with 16.1 months among women taking the placebo who got the disease in the placebo arm.

A trend to more cases of the disease in women taking the hormones.

All told, there were 67 deaths among the 8,052 women on hormones and 37 among the 7,678 women in the placebo group, Chlebowski said.

He added that, while smoking behavior was balanced between the study arms, smoking and taking the hormones led to an increase in the risk of death from the disease.

About one in 100 current smokers in the study had an avoidable cancer deaths associated with the combined hormone therapy, he said.

"Women almost certainly shouldn't be using both combined hormone therapy and tobacco," he said.

The finding is "a bit in contrast to the majority of case-control studies, where you see either no difference or a reduced risk," said Dr. Bruce Johnson of the Dana-Farber Cancer Institute in Boston, who was not part of the study.

"This is likely more accurate," he said, "since this is controlled in a prospective randomized study."

The study was supported by the NIH. The researchers reported financial links with Amgen, AstraZeneca, Eli Lilly, Novartis and Wyeth. Johnson reported financial links with Genzyme, Boston Scientific, Celgene, and Johnson and Johnson.