A sharp decline in U.S. breast cancer deaths in 2003 held steady the following year, providing further evidence that the drop is related to the large number of women who stopped hormone replacement therapy, researchers report today.
Between 2001 and 2004, the number of breast cancer cases dropped 8.6% overall -- 11.8% among women older than 50, the primary consumers of the hormones, according to the study in the New England Journal of Medicine.
The continued decline shows that the drop in cases "was not a one-year wonder, a short-lived anomaly," said one of the study's authors, Dr. Peter Ravdin of the University of Texas M.D. Anderson Cancer Center.
Over the two-year study, 30,000 fewer women developed breast cancer than would have been expected from previous trends, and the incidence reached its lowest rate since 1987. An estimated 200,000 cases are diagnosed each year.
"We can't prove" that decreases in hormone therapy caused the decline in breast cancer, "but it is such a substantial reduction that you would need something big to have occurred to explain it," said coauthor Dr. Rowan T. Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. "If it is not hormone replacement therapy, we still need to explain it."
Independently, in an online paper in the journal Lancet, British researchers linked hormone replacement therapy to a 20% increase in the risk of ovarian cancer. They calculated that there were an additional 1,300 cases of ovarian cancer and 1,000 deaths in the United Kingdom between 1991 and 2005 resulting from the treatment.
In the 1990s, hormone replacement drugs were among the most prescribed medications for women older than 50, with more than 90 million prescriptions written in the U.S. each year for 15 million women. The therapy controlled symptoms of menopause and was thought to reduce the risk of heart disease.
That changed abruptly in mid-2002, when a large study known as the Women's Health Initiative showed an increased risk of breast cancer associated with the treatment.
Prescriptions for the drugs, generally a combination of estrogen and progestin, plummeted by at least 38% in 2003 and by an additional 20% in 2004.
In December, Ravdin and his colleagues reported at the San Antonio Breast Cancer Symposium that the incidence of breast cancers had dropped nearly 7% in 2003, and argued that the decline was caused by the drop in hormone replacement therapy.
Critics argued that the results could have represented an aberration, and urged caution until more results were available.
Perhaps the most telling evidence from the new study was that the biggest decline, 14.7%, was in estrogen-receptor-positive tumors -- cancers in which estrogen promotes tumor growth. For estrogen-receptor-negative tumors, the decline was only 1.7%.
Critics, such as the International Menopause Society and the American Society for Reproductive Medicine, argued that the decline could be explained in part by a 3% reduction in mammography rates during the period and that similar reductions in breast cancer incidence had not been observed in other countries, though hormone use had fallen there as well.
Dr. Joseph Camardo of Wyeth Pharmaceuticals, one of the leading manufacturers of estrogen replacements, noted that there was not a sharp decline in 2004, though hormone use fell an additional 20% that year.
They also argued that the rapid decline in incidence so soon after the drop in hormone use was biologically implausible.
But the researchers noted that therapy that reduces the amount of estrogen reaching tumors also produces a quick response in tumor growth.
Removing the estrogen therapy might even have killed very small tumors, Chlebowski said.
Chlebowski believes that other countries will soon report similar declines in breast cancer rates. "The methodology by which cancer incidence is reported will come under close scrutiny," he said.
The new ovarian cancer results came from the Million Women Study, in which researchers monitored 948,756 post-menopausal women for five years.
Epidemiologist Valerie Beral and her colleagues at the Cancer Research UK Epidemiology Unit at the University of Oxford found that the excessive risk was directly related to the length of time the women remained on hormone replacement therapy and to the dosage consumed.
They found that the risk returned to normal, however, when the therapy was halted.
Chlebowski noted that the Women's Health Initiative found a slight trend toward increased risk for ovarian cancer, but the study of nearly 17,000 women was not large enough to give significant results.
In an editorial accompanying the Lancet paper, Dr. Steven Narod of the University of Toronto said: "With these new data, we expect the use of [hormone replacement therapy] to fall further. We hope that the number of women dying of ovarian cancer will decline as well."
Wyeth's Camardo noted that the labeling for hormone replacements already carries a warning about the potential risk of ovarian cancer.
Ravdin said the authors were not recommending that all women stop taking the drugs. "The risk of developing breast cancer from use of these hormones is relatively small, and for some women with post-menopausal symptoms, the benefits are well worth the risk," he said.
Experts said that women who took them should use the lowest possible dose for the shortest possible time.