A new drug may profoundly reduce women's odds of getting breast cancer, according to eagerly awaited data to be released by researchers today.
The drug, raloxifene, recently gained Food and Drug Administration approval for the prevention of the bone-thinning disease osteoporosis in post-menopausal women. But breast cancer prevention advocates and others have been watching the drug closely during the past several months, as hints of its potential power to prevent breast cancer began to emerge at scientific meetings.
At a conference in Los Angeles, doctors are scheduled to provide the first formal release of those data. Compared with those who took dummy pills, post-menopausal women who took one tablet of raloxifene daily had about one-third the odds of getting invasive breast cancer after two years.
"To see a 70 percent overall reduction in risk is astounding," said Steven Cummings, a professor of medicine and epidemiology at the University of California, San Francisco, who with V. Craig Jordan of Northwestern University led the key raloxifene studies.
Unlike tamoxifen, the only drug until now shown to cut the chances of developing breast cancer, raloxifene so far seems not to increase the risk of endometrial cancer. And raloxifene's ability to prevent breast cancer appears to extend to women who are not at especially high risk for the disease -- something that has not been demonstrated with tamoxifen.
But some scientists and patient advocates cautioned against reading too much into the new results. The raloxifene studies have not gone on long enough to generate trustworthy numbers, they said. And in any case, the studies were designed specifically to look at the drug's effects on osteoporosis, not breast cancer. Not all women had annual mammograms to look actively for new breast cancers, for example, and only a fraction of participants received regular gynecological exams to watch for endometrial cancer.
Some activists also charged that the significance of the early results was being exaggerated by the drug's manufacturer, Eli Lilly, or others in an effort to boost sales of the drug -- a charge that the company disputed. Doctors can prescribe approved medicines for nonapproved purposes, and many companies derive substantial profits from such "off-label" sales.
"I'm very disturbed about the hype around this drug," said Fran Visco, president of the National Breast Cancer Coalition, a patient advocacy group in Washington.
"I don't know if Lilly is to blame," Visco said. "But I do know that at a number of different conferences I've attended, [researchers] have gotten up and spoken of it like a miracle drug. They actually use those words, 'a miracle drug,' and we have to spend a lot of time telling women we have no information that this is a miracle drug."
Little can be determined about a drug's potential to prevent breast cancer after just two years, since the disease takes many years to develop, Visco and others said.
Critics especially took issue with the suggestion by some researchers that raloxifene appears to lower women's risk of endometrial cancer, a form of uterine cancer. Related drugs used to prevent osteoporosis, such as Premarin and tamoxifen, increase by twofold to threefold the odds of getting that relatively rare cancer. If raloxifene can offer similar benefits without raising the incidence of uterine cancer, it could leap to the fore of a $1 billion market.
The initial findings on endometrial cancer do appear encouraging at first glance. Cummings reported that raloxifene reduced the risk of that cancer by 50 percent in the first two years, and perhaps by as much as 75 percent.
But that's based on only eight cases to emerge in the study so far. Although most of them were in women taking dummy pills, the number is so small that the apparent benefit of raloxifene may be due to chance. In fact, a strict statistical analysis of those numbers indicated that it is impossible to say whether raloxifene lowers, leaves unchanged or raises a woman's risk of endometrial cancer.
Leslie Ford, associate director of the National Cancer Institute's early detection and community oncology program, said it is far too soon to conclude that raloxifene is a benign drug. "The risk of endometrial cancer with tamoxifen was not recognized for more than 10 years," she warned. "These are rare diseases, and it can take a long time to see if there is a trend."
Studies have shown that raloxifene increases the number of potentially dangerous blood clots, although no more so than tamoxifen or Premarin. The most common side effect of raloxifene is hot flashes.
Raloxifene is one of a new class of drugs that mimic the hormone estrogen in some tissues and work in opposite ways in other tissues. Researchers hope such drugs will be able to serve as a replacement for the estrogen no longer made by a woman's ovaries after menopause, offering the hormone's positive protective effects on the heart and bones but without the increased risk of breast or uterine cancer that can come with standard estrogen.
Speaking at the annual meeting of the American Society for Clinical Oncology, Northwestern's Jordan said a total of 49 cases of breast cancer had been diagnosed in all of the approximately 10,500 women ever to have been involved in a clinical trial of raloxifene. By comparing the number of cases that arose in women who were getting the drug with the number of cases that arose in women who got placebos, he concluded that raloxifene reduces the risk of breast cancer by 54 percent.
Cummings reported on a subset of that group consisting of 7,705 women. All of them were past menopause but none was at especially high risk of breast cancer -- typical of the kind of woman diagnosed with breast cancer today. Raloxifene reduced the odds of getting breast cancer by 70 percent in this group and by 87 percent when counting only "estrogen-dependent" breast tumors, the most common kind of breast cancer in older women.
Cummings said it will be important to continue the raloxifene study for many years, since women may want to take the drug on a long-term basis. Recent studies of tamoxifen have suggested that if women take it for longer than five years, it may increase, rather than decrease, their risk of breast cancer.
Further complicating the question of whether women should consider taking raloxifene or any of the other bone-preserving drugs after menopause, a study last week found that raloxifene improved cholesterol levels and generally lowered the risk of heart disease -- the No. 1 killer of women -- but not to the extent seen with Premarin and tamoxifen.
That means women will have to weigh the various risks and benefits of these drugs against their own personal assessment of their odds of getting cancer, heart disease or other diseases, experts said.
Lilly and the National Cancer Institute are planning a large, multi-year clinical trial that will compare tamoxifen with raloxifene directly.
That study, to include 22,000 women and to start perhaps by this fall, would be the first to specifically test raloxifene's effects on breast and endometrial cancer.
Breast cancer is the most commonly diagnosed cancer in women and the second biggest cause of cancer death among women, striking an estimated 178,700 women and killing 43,900 each year.
Also at the conference yesterday, researchers released results of preliminary studies into another drug, Herceptin, that targets a specific protein in the body linked to very aggressive, quick-killing breast cancers. Herceptin appeared to slow or stop the progression of advanced disease, according to Dennis Slamon of the University of California, Los Angeles, the principal investigator.
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