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Breast cancers drop as hormone use is cut

Study helps explain mystery of the disease

WASHINGTON -- New federal statistics provide powerful evidence that the sharp drop in hormone use by menopausal women that began in 2002 caused a dramatic decline in breast cancer cases, according to an analysis being published today.

The statistics show that the number of women diagnosed with breast cancer abruptly began falling after concerns emerged about the safety of hormone treatment and that the decrease persisted into the following year, strengthening the case that the trends are related, researchers said.

"At first I didn't believe it -- it was so astounding," said Donald Berry of the University of Texas, who led the analysis published in The New England Journal of Medicine. "But it really looks like it's a story that holds together."

Based on the findings, the researchers estimated that about 16,000 fewer cases of breast cancer are being diagnosed each year because of the precipitous fall in hormone use, a stunning reversal of a decades-long increase in cases.

"This is colossal," said Rowan Chlebowski of the Harbor-UCLA Medical Center, who helped conduct the analysis. "It translates into thousands of fewer breast cancers that have been diagnosed in women in the United States and could be in the future."

The findings also help explain one of the biggest mysteries about breast cancer -- why the number of cases rose steadily for decades. Increasing hormone use probably played a key role, along with better detection by mammography and other factors, several analysts said.

"I think this solves at least part of the mystery," Berry said.

Others said the findings underscored the danger of drug therapies becoming widespread before they have been carefully tested.

"An awful lot of breast cancer was caused by doctors' prescriptions," said Larry Norton of Memorial Sloan-Kettering Cancer Center in New York. "That's a very serious and sobering thought."

Norton and others said the findings should encourage more women to discontinue hormone use, or take them at the lowest dose for the shortest time necessary.

"These data add to the message that we really should be discouraging women from initiating menopausal hormones," said Marcia L. Stefanick of Stanford University. "We need to stop underplaying those risks. They are very real."

Some researchers, however, questioned the findings, saying the drop in breast cancer occurred too soon to have been caused by the decline in hormone use.

"Even if there was a cause-and-effect, you wouldn't expect it to show up for five or 10 years," said Hugh Taylor of Yale University. "It just doesn't fit with what we know about the basic biology of breast cancer."

Wyeth Pharmaceuticals, which makes the most widely prescribed hormones, also questioned the link, saying hormone use continued to fall while the breast cancer rate remained stable after the initial drop. The researchers, they said, had failed to rule out other causes, such as a decline in mammogram use.

"We do respectfully disagree with the conclusion here," said Joseph Camardo, Wyeth's senior vice president of global medical affairs.

Millions of women took hormones for years to alleviate hot flashes and other symptoms of menopause and in the belief they were a virtual fountain of youth -- boosting energy, preventing wrinkles, and providing a host of health benefits, including reducing the risk of heart disease.

In 2002, however, the large federal Women's Health Initiative study stunned doctors and patients when it showed that the hormones not only failed to protect women's hearts, they appeared to increase the risk of heart attacks and strokes, as well as breast cancer and other health problems. The news prompted millions of women to abandon the drugs.

Researchers first reported last fall that the breast cancer rate had dropped in 2003 after rising steadily since the 1980s, and that the drop appeared to coincide with the news about hormones. Experts have been waiting for the latest federal data, from 2004, to see if the trend persisted.

The new analysis showed that the breast cancer rate began falling almost immediately after the Women's Health Initiative findings were released in July 2002, dropping 6.7 percent between 2002 and 2003. The 2004 data showed that the rate remained at the lower level, having fallen 8.6 percent between 2001 and 2004.

The researchers said that indicates the drop was due primarily to the decrease in hormone use and not other factors, such as fewer women getting mammograms, greater use of hormone-blocking drugs like tamoxifen or some unknown change in the environment, and that it will be long-lasting.

"The fact that the incidence rate did not go back up suggests that the effects will be long-lived," said Peter Ravdin of the University of Texas, who helped conduct the analysis.

The link is strengthened by the fact that the decline occurred primarily in women ages 50 to 69, the age group most likely to use hormones, and predominantly in a form of breast cancer sensitive to the hormone estrogen. New cases of this type fell 14.7 percent, the researchers said.

The researchers and others stressed that further research will be needed to determine whether the reduction in diagnoses will translate into fewer deaths.

Researchers suspect hormone use may mostly spur the growth of tumors that may never become life-threatening. In the absence of hormones, they may remain small enough to never be detected by mammograms or may even shrink.

"Think of a cancer that you are feeding with hormones and now you stop the fuel. What's going to happen to it?" Berry said. "Most likely it stops growing and stays under the radar, or maybe even regresses. It could even disappear."

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