When research works
By Ruth SoRelle, M.P.H.
Last month, a study of new cases (called incidence) of breast cancer in the United States in 2003 showed a sharp decline, and colleagues at The University of Texas M.D. Anderson Cancer Center (who led the study) and other medical institutions opined that the drop may be related to the fact that millions of older women stopped taking hormone replacement therapy in 2002.
The reason so many women stopped was that a federally funded study of menopausal women across the nation showed that more women who took hormone replacement therapy developed breast cancer, heart problems, strokes and blood clots than did those who did not. This study – called the Women's Health Initiative – was the first really large one in the United States directed at issues that affect women's health.
Only 2.5 percent of women in the WHI had any of the above problems, but the differences between the groups – those who took hormone replacement of estrogen and progestin and those who did not – was striking enough that the study's organizers, with the concurrence of the sponsoring National Heart, Lung and Blood Institute, decided to end the study early in 2002. Simply, the risks outweighed the benefits.
A total of 16,608 women ages 50 to 79 were enrolled in the estrogen-progestin arm of the trial. It was a large study with enough participants to answer the question. Yet, when the question was answered, many were so shocked that they were skeptical of the results.
Claude Lenfant, M.D., then director of the NHLBI, was not. He said, "We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from WHI is that this combined form of hormone therapy is unlikely to benefit the heart. The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits – and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures."
Many who led the study, including some with the Baylor College of Medicine WHI Center, remembered that some of their colleagues questioned their ethics in conducting such a trial. The critics said the benefits of hormone replacement therapy were so obvious that it would not be fair to have a group that was not receiving hormones.
In 2004, a concurrent study of estrogen alone in women who had had their uteruses was also stopped early when researchers again found that the risks outweighed the benefits. That study showed that estrogen alone increased the risk of strokes and blood clots in the legs, decreased the risk of hip fractures, and had no clear effect on heart disease or breast cancer.
The newest study, led by the M.D. Anderson researchers and presented at the 29th Annual San Antonio Breast Cancer Symposium, showed a 7 percent relative decline in new breast cancer cases between 2002 and 2003. The steepest such decline – 12 percent of cancers known to be responsive to estrogen (so-called estrogen-receptor positive breast cancer) – occurred in women between the ages of 50 and 69. They concluded that as many as 14,000 fewer women were diagnosed with breast cancer in 2003 compared to 2002.
The only difference that they could find was the fact that after the first report of findings from the Women's Health Initiative in 2002, millions of women stopped taking hormone replacement therapy.
It may take years to say definitely what caused the drop. It will be exciting to see if the decline continues in years to come.
But for the researchers in the Women's Health Initiative – including those involved in the study site at Baylor College of Medicine – the results show that they were right to question what seemed to many to be a foregone conclusion.
In science – particularly science that affects people's health – it is never acceptable to assume that something works, even when it seems to make sense. Only large studies that look carefully at the effects of such treatment can determine for certain whether a treatment actually has the desired effect. As the current statistics seem to show, a negative study can have as great an impact as a positive one.
