Breast Cancer Drop
Tied To Less Hormone Use

ROB STEIN / Washington Post 19apr2007

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 breast cancer cases being diagnosed began falling abruptly 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 A. 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."

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

"This is colossal," said Rowan Chlebowski of 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 experts said.

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

Others said the findings underscore the danger of drug therapies becoming widely used before they have been thoroughly 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 stop hormone use altogether or to continue at the lowest dose and for the shortest time necessary.

The findings come as another study involving nearly 1 million British women found that hormones also increase the risk of ovarian cancer.

"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. Some also viewed hormones as a virtual fountain of youth — boosting energy, preventing wrinkles and providing 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 year 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 primarily caused by the decrease in hormone use and not other factors, such as fewer women having mammograms, greater use of hormone-blocking drugs such as tamoxifen or an 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 estrogen. New cases of this type fell 14.7 percent, the researchers said.

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

Researchers suspect hormone use may spur the growth of tumors that may never become life-threatening. Without hormone use, the tumors may remain small enough to never be detected by mammograms. They 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."

source: 19apr2007

Breast-Cancer Data Pose Puzzle

TARA PARKER-POPE / Wall Street Journal 19apr2007

A new report shows breast-cancer incidence remains at its lowest rate in 20 years, but it raises more questions than it answers about why an estimated 16,000 fewer women in the U.S. have been diagnosed with the disease.

The data, published in a special report in the New England Journal of Medicine, offer an extended analysis of breast-cancer statistics for 2003 and 2004. The data are important because they affirm that a steep decline in breast cancer that occurred in 2003, first reported in December, wasn't an anomaly.

Researchers from the University of Texas' M.D. Anderson Cancer Center and the University of California, Los Angeles, have speculated that the big drop may be explained, at least in part, because millions of women abruptly stopped using menopause hormones in mid-2002.

At the time, a major government hormone study was halted because of fears that older women in the study who used hormones had higher rates of heart attacks and breast cancer. The study results frightened women, causing a decline of about 20 million prescriptions — or about 38% — in the months after the announcement.

Although changes in hormone use may explain some of the drop in breast-cancer incidence, experts speculate other factors are probably involved. One big worry is that a portion of the decline may be due to fewer women getting mammograms. That would mean women aren't really being spared from cancer, but that doctors just haven't found it yet, because women aren't showing up to be screened.

"Some women become less vigilant about having regular mammograms after stopping hormone therapy," says JoAnn E. Manson, Harvard University epidemiologist and investigator for the Women's Health Initiative study of menopause hormones. "If so, some of the decline in rates could reflect underdiagnosis."

In addition, increased use of medications such as the bone drug raloxifene, aspirin and anti-inflammatory drugs and of calcium supplements and Vitamin D — all of which are linked with lower breast-cancer risk — may also help explain the decline.

"It's probably the combination of a lot of things that may be contributing to this change," says oncologist Dawn Hershman, assistant professor of medicine and epidemiology at Columbia University Medical Center. "We probably need another couple years of data to fully understand it."

Peter Ravdin, the Texas researcher who led the new study, says the good news is that after the big drop in breast cancer in 2003, the number of cases leveled off in 2004, rather than increased, as many feared would happen. That shows the drop "was not a one-year wonder," he says.

Although the reasons for the decline are probably complex, Dr. Ravdin says much of the evidence points to changes in hormone use. He notes that the drop was seen in women over 50, the same age group that uses menopause hormones. In addition, the biggest declines were seen in the type of tumor most affected by hormones. Although the number of breast-cancer cases dropped by 8.6% from 2001 to 2004, the number of estrogen receptor-positive breast cancers fell by about 15% during that period.

But even if the drop is linked to hormones, what isn't clear is whether it is a temporary dip or a permanent decline. It may be that stopping hormones — which are known to fuel tumorgrowth — may have simply slowed or delayed tumors but that they will show up eventually. "That's the real question" says Dr. Hershman. "Did you actually change anything, or did you just slow it down?"

Experts say the breast-cancer data don't change the fact that menopausal women should use hormones to treat distressing hot flashes and other symptoms, in the lowest dose for the shortest time possible. "I wouldn't want this to be something that caused all women to stop hormone replacement therapy,'' Dr. Ravdin says.

Researchers noted that stopping hormone therapy doesn't dramatically change an individual woman's overall risk for breast cancer. Based on the latest analysis, a woman who stops hormones would, at best, reduce her individual risk of developing breast cancer by just 1 in 60, or about 1.7 percent, say researchers.

Researchers at the University of California, San Francisco are reviewing data on hundreds of thousands of women who take part in a national breast screening program. That analysis should help clarify whether less screening is affecting breast-cancer incidence.

"It looks like incidence has gone down, and that's good,'' says Karla Kerlikowske, the UCSF epidemiology professor who is conducting the new analysis. "But it's unclear how much of that decrease is potentially from hormones and how much is from changes in screening. You just can't tell.''

In an unrelated study, the Lancet medical journal reported that a major British study of hormone use, called the Million Women Study, found that hormone users were at higher risk of ovarian cancer than nonusers. The Women's Health Initiative showed no statistically significant increase in risk of ovarian cancer among hormone users.

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Local Radiotherapy to Contribute to
Leukemia Risk in Breast Cancer

American Association for Cancer Research 19apr2007

Radiation therapy affects not only the cancer mass, but also the surrounding tissues, including the bone marrow. Signals from the cells in the bone marrow damaged by cancer radiotherapy could be involved in the development of secondary acute myeloma by drawing hematopoietic stem cells, the blood-producing cells of the bone marrow, from distant sites into the irradiated bone marrow, according to researchers from the Ontario Cancer Institute.

Their findings suggest that local radiotherapy leads to leukemia, even though radiotherapy directly affects only a small fraction of the bone marrow.

While often effective in treating breast cancer, localized radiation therapy increases the risk of developing secondary cancer, which most frequently manifests in the form of acute myeloid leukemia. In breast cancer, less than 10 percent of bone marrow is exposed to radiation therapy, yet a much higher percentage of hematopoietic stem cells could be affected.

To understand this effect, the researchers labeled and tracked the movement of hematopoietic stem cells in an animal model. Following local radiation therapy, they found that more than four times more hematopoietic stem cells accumulated in the irradiated bone marrow, compared to the non-irradiated bone marrow. Through molecular screening, they found that cells in the area were creating an overabundance of three protein signals known to recruit hematopoietic stem cells: SDF1, MMP2 and MMP9.

"Cells within the bone marrow send out these chemical signals as a sort of call for help, which recruits a large number of hematopoietic stem cells into the affected areas, supposedly to replace damaged cells," said Carlo Bastianutto, Ph.D., a scientific associate at the Ontario Cancer Institute. "In effect, this becomes a trap for this specific population of stem cells, drawing them into the bone marrow present in the radiation field and getting them exposed to the following radiation cycles. This story might repeat at every cycle of radiation therapy, therefore increasing the chance of producing a leukemic stem cell."

According to the OCI researchers, the recruiting signal might be stopped by chemical blockers, which was shown to inhibit the signals experimentally. "Conceivably, it could be possible to inhibit these chemical signals, and this could reduce the risk of secondary acute myeloid leukemia, but much more research needs to be done," Bastianutto said.

The researchers believe this model could help prevent acute myeloid leukemia in patients with malignancies other than breast cancer.

source: 19apr2007

Hormone Replacement Therapy
Linked to Ovarian Cancer

Australian Broadcasting Corporation 19apr2007

A study has found that hormone replacement therapy (HRT), a contested treatment for post-menopausal women that has already been linked to breast cancer, is also associated with ovarian cancer.

The research, published in The Lancet, has found that women who take HRT are 20 per cent more likely to develop and die from ovarian cancer than women who have never been on the treatment.

The evidence comes from a major British investigation into female health, the Million Women Study, covering 1.3 million British women from 1996 to 2001.

HRT entails taking substitutes for oestrogen or progesterone after natural levels of the key female hormones diminish after menopause.

The idea behind it is to reduce symptoms such as hot flushes and vaginal dryness and boost protection against osteoporosis and heart disease.

The British researchers assessed data from 948,000 post-menopausal women, who had been questioned and later given a follow-up exam three years later.

Around 30 per cent were current HRT users, 20 percent had previously received HRT and the remaining 50 percent had never taken it.

Across all three groups, a total of 2,273 women developed cancer and 1,591 died from it.

The increased risk of cancer was shouldered by current HRT users, especially those who had been taking the hormones for at least five years.

The risk was largely unchanged by such factors as a smoking habit or past use of oral contraceptives.

Women who had stopped HRT had the same risk level as counterparts who had never taken the treatment.

Lead researcher Professor Valerie Beral says women who want to take HRT should do so for as short a time as possible.

"It's more an issue for women to think about how much they want to take HRT to relieve their symptoms against the known risks and it's really up to women in discussion with their doctors to try and work that out," she said.