Hormone replacement therapy, already linked to increased risk of breast cancer, heart disease and stroke, nearly doubles a woman's risk of dying from lung cancer, researchers reported Saturday in a finding that may be the final blow for a therapy that is already in rapidly declining use.
The findings "seriously question whether hormone-replacement therapy has any role in medicine today," Dr. Apar Kishor Ganti of the University of Nebraska Medical Center wrote in an editorial accompanying the online publication of the report in the medical journal Lancet.
The link to lung cancer "is yet another reason to not use hormone replacement therapy if it can be avoided," said Dr. Mark Faries of the John Wayne Cancer Institute in Santa Monica, who was not involved in the research. "It raises the bar for deciding to do HRT."
The findings come from the Women's Health Initiative, a large study originally begun in 1991 to demonstrate, in part, that administering estrogen and progestin could relieve debilitating symptoms of menopause and reduce the risk of heart attack and stroke. The hormone replacement part of the study, which enrolled more than 16,000 women, was halted prematurely after about 5 1/2 years when it was observed that the risks far outweighed any potential benefits.
Not only did the therapy not protect against heart disease and stroke, but it also yielded questionable improvements in quality of life and produced a small but statistically significant increase in the risk of heart disease, stroke and breast cancer. Several subsequent reports have shown that breast cancer rose by at least 15% during the 1990s when HRT was blooming, then dropped sharply when many women abandoned the treatment after a 2002 report.
Treatment with estrogen has a deleterious effect on breast cancer patients because the hormone binds to estrogen receptors on tumor tissue, accelerating its growth. Recent studies have shown that lung tissue also has estrogen receptors and that the accelerated growth is even more dramatic in lung tumor cells, according to Dr. Richard J. Pietras, who directs the Stiles program on oncology at UCLA's Jonsson Comprehensive Cancer Center.
"We've been suspecting for a long time that this is an area we need to investigate," Pietras said. The incidence of lung cancer in women has been growing, and more women die from it than from breast, ovarian and colon cancers combined. About 99,000 women are diagnosed with lung cancer each year, and 71,000 die from it.
The first results from the Women's Health Initiative suggested that the hormones might affect lung cancer. To further explore a link, Dr. Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and his colleagues studied the women in the initiative for an additional 2 1/2 years.
They found that 109 women who received hormone treatments had been diagnosed with lung cancer, compared with 85 in the group that received a placebo -- a modest 23% increase in incidence.
The difference was more dramatic when they considered deaths. In the group receiving hormone therapy, 73 died, compared with 40 in the placebo group, a 71% increase. The increase in lung cancer deaths accounted for half of the overall increase in deaths in the hormone therapy group, Chlebowski said. The effect was most pronounced for so-called non-small-cell lung cancer, the most common form in women. There were 62 deaths from this type of tumor in women receiving hormones, compared with 31 deaths in the placebo group.
The findings "have special significance" for women who are now or have been heavy smokers, Chlebowski said.
Smokers who took hormone therapy had a 1% chance of dying from lung cancer in five years. Women who had smoked in the past had about half that risk. "About half the post-menopausal women in the United States would fall into either category," he said.
The findings suggest that the hormones do not cause lung cancer, but that they accelerate the growth of existing tumors, making them more aggressive and more likely to metastasize, Chlebowski said.
Lung cancer is "a very potent, brutal disease," said Dr. Glen Justice, director of the MemorialCare Cancer Institute at Orange Coast Memorial Medical Center in Fountain Valley. "The real take-home message here is that you have got to have a very good reason for going on hormones because we now know that there are so many negative effects."