Hormone replacement therapy, already linked to increases in 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 nail in the coffin 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, director of translational tumor immunology at the John Wayne Cancer Institute in Santa Monica, Calif.
The findings come from the Women’s Health Initiative, a large study originally begun in 1991 to demonstrate, in part, that administration of a combination of estrogen and progestin could relieve debilitating symptoms of menopause and reduce the risk of heart attack and stroke. The hormone replacement arm, 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.
The therapy not only did not protect against heart disease and stroke, but it yielded only 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 the rate of breast cancer rose by at least 15 percent during the 1990s when HRT was blooming, then dropped sharply when many women abandoned the treatment after a 2002 report on the subject.
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 laboratory studies have shown that lung tissue also has estrogen receptors and that the accelerated growth is even more dramatic in lung tumor cells.
The first results from the Women’s Health Initiative suggested that the hormones might have an effect on 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 Women’s Health Initiative for an additional 2 1/2 years.
At the end of the eight-year period, they found that 109 women who received the estrogen and progestin treatments had been diagnosed with lung cancer, compared with 85 in the group that received a placebo – a modest 23 percent increase in incidence.
The difference was more dramatic when they considered deaths. In the group receiving hormone therapy, 73 women died, compared with 40 in the placebo group, a 71 percent increase.
The findings suggest that the hormones do not themselves cause lung cancer, but that they accelerate the growth of existing tumors, making them more aggressive and more likely to metastasize, Chlebowski said.