The drugs work by blocking the effects of estrogen in breast tissue, lowering the chance of hormone-related cancers. But they also increase the risk of blood clots and hot flashes, among other side effects - so they shouldn't be handed out to everyone, the U.S. Preventive Services Task Force (USPSTF) said in its new draft guidelines.
"Currently only a minority of women for whom the medication might be indicated are actually taking it," said Dr. Mark Ebell, a member of the Task Force from the University of Georgia College of Public Health in Athens.
"I don't think there's a right or wrong answer for women," he told Reuters Health. "The main thing is just for women to be aware of this as an option and to talk to their doctor if they think they might be at increased risk."
Women are considered at high risk if they have a five-year chance of developing breast cancer of at least one in 60. Tools such as the Gail model take into account a woman's age, race, personal history of breast exams and family history of cancer to estimate her own risk of breast cancer.
A review conducted for the USPSTF and published concurrently found tamoxifen (marketed as Nolvadex and Soltamox) and raloxifene (Evista) decreased women's chances of developing breast cancer by 30 to 56 percent.
Both drugs also doubled the risk of blood clots and tamoxifen increased the chance of endometrial cancer and cataracts, according to findings published in the Annals of Internal Medicine.
The review did not include studies that focused on women with breast-cancer related BRCA gene mutations.
Angie Fagerlin, a bioethicist from the University of Michigan Medical School and the Ann Arbor VA, said it's important to consider an approximately 50-percent relative reduction in breast cancer risk in context.
For a woman who starts out with a one in 40 chance of developing cancer, she told Reuters Health, "Your risk goes from 2.5 to 1.25 (percent). It's a 1 percent difference in your risk of breast cancer, having to take a drug every day for five years that has some side effects."
But for some women who have a much higher short-term risk of breast cancer - as high as 16 percent - the drugs are more likely to be worth potential side effects, said Fagerlin, who wasn't involved in the new review or the Task Force decision.
"There are a lot of things that play into this decision," she said. "Women should know that this is an option, and they should be told their risks and benefits in a way they can understand."
‘TAKE A TEST RUN'
About one in 8 women will be diagnosed with breast cancer during her lifetime and one in 36 will die of the disease, according to the American Cancer Society.
The new draft recommendations echo guidelines released by the Task Force a decade ago but now have more evidence behind them, according to Ebell. They will be posted for public comment until May 13 here.
Other doctor groups, including the American Society of Clinical Oncology, also recommend some women at high risk of breast cancer be offered tamoxifen or raloxifene.
Elissa Ozanne, who studies decision science at the University of California, San Francisco, said the most common problems reported with tamoxifen and raloxifene include hot flashes and other "quality-of-life" side effects.
"The serious ones are very rare," Ozanne, who wasn't involved in the new research, told Reuters Health. If women are worried about side effects and how they might feel on the drugs, she added, "It's something that they could try out and take a test run of it."
Generic tamoxifen can be bought for about $100 per month or less.
Ozanne pointed out that research suggests women can reduce their risk of breast cancer through lifestyle changes, as well as medication.
"There are a lot of things women can think about doing, and tamoxifen is one of them, and so are things like maintaining a healthy body weight," she said.
On Monday, an influential panel of experts said that the answer is yes, but only for certain women who are at increased risk because of breast cancer in the family or a personal history ofbreast lumps or other problems. Two drugs, tamoxifen and raloxifene, can lower the risk, and may be worth taking even though both can have serious adverse effects like blood clots and strokes, the experts said.
The panel, the United States Preventive Services Task Force, recommended that for healthy women ages 40 to 70, doctors helpassess the odds of breast cancer and offer to prescribe one of the drugs for patients whose risk is above average — but only if their chances of developing blood clots and strokes is low.
Because of the adverse effects, the panel also advised that the drugs not be prescribed for women unless they are at increased risk of breast cancer.
“There is evidence of benefit for certain women,” said Dr. Wanda K. Nicholson, a task force member and an associate professor of obstetrics and gynecology at the University of North Carolina School of Medicine in Chapel Hill.
Dr. Nicholson said she recommended the drugs for some of her own higher-risk patients. Some take them; some choose not to.
“The take-home point for women is to have that initial conversation with their provider,” she said.
The task force recommendations are being published in draft form and are open for public comment until May 13. An analysis of research on which the recommendations were based was also being published in Annals of Internal Medicine. The advice matches that given by the task force in 2002 (the group re-evaluates many of its subjects once a decade), though the earlier report stopped short of telling doctors to offer to prescribe the drugs. Members of the group said they relied on a wealth of new data that helped confirm and clarify the risks and benefits of the two drugs, and how they measure up against one another.
Tamoxifen and raloxifene have been recommended for years for women whose odds of developing breast cancer are higher than average. Both drugs block the effects of estrogen, and can lower the risk of the type of breast cancer whose growth is stimulated by the hormone. About 75 percent of breast cancers fall into that category. Tamoxifen is more commonly used to prevent recurrences in women who have already had breast cancer, and raloxifene is most often prescribed to prevent fractures in women with osteoporosis. Tamoxifen can also decrease the risk of fractures.
Doctors may see these drugs as a rare opportunity to lower the risk of cancer, but some women see them as simply trading one risk for another. Many healthy women, even if they are at increased risk, refuse the drugs, asking why they should take pills to lower the odds of a disease they may never get anyway, especially when the drugs can have dangerous or unpleasant side effects.
Besides increasing the risk of blood clots and strokes, the drugs can also cause hot flashes and vaginal problems like dryness and pain that can damage a woman’s sex life. In addition, tamoxifen can lead to cataracts and uterine cancer.
In the United States, 232,000 new cases of breast cancer are expected this year, and about 40,000 women will die from the disease.
The group estimated that among 1,000 women with an increased risk of breast cancer, there would be 23.5 cases of invasive breast cancer over five years. If the women took one of the drugs, 7 to 9 cases would be prevented over five years.
But an extra 4 to 7 women per 1,000 taking the drugs would develop blood clots during that time, and there would be 4 extra cases of uterine cancer per 1,000 women taking tamoxifen — an approximate doubling of both of those risks. Women who had surgery to remove the uterus would not have to worry about that type of cancer.
The task force considered a woman likely to benefit from the drugs if her odds of developing breast cancer during the next five years were 3 percent or higher. One common method of estimating the risk uses an online tool that asks a series of questions about the patient’s health and family history. It calculates her risk, and compares it to the average for women of that age.
At age 40 the average woman has a 0.6 percent risk of developing breast cancer over the next five years; at age 50, 1.3 percent; at age 60, 1.8 percent; at age 70, 2.2 percent. Plugging risk factors into the calculator, like mothers or sisters with breast cancer, or a personal history of breast biopsies, makes the risk go up.
But experts warn that although these estimates can be useful in predicting the risk for large populations, they do not work very well for individuals.
The report from the task force states: “Most women identified as ‘high risk’ will not develop breast cancer, and the majority of breast cancer cases will arise in women who are not identified as having increased risk.” The group also noted that the type of risk calculator generally used is not recommended for women with mutations in BRCA genes, which greatly increase the risk of breast cancer.
Dr. Heidi Nelson, a research professor at Oregon Health and Science University in Portland, Oregon, led a team that analyzed several large controlled studies. They found that the drugs could reduce the incidence of invasive cancer by 30 percent to 68 percent, compared with placebos. A new finding is that tamoxifen had a greater protective effect than raloxifene. But it was more likely to cause blood clots. Women over 50 were more likely to develop blood clots from the drugs, or uterine cancer while taking tamoxifen.
Dr. Nelson noted that some studies found women would be more willing to take the drugs if they could prevent breast cancer entirely, rather than just lowering the risk, or if the drugs had no side effects.
One thing that might help doctors and patients, she said, is to keep in mind that the adverse effects were more common in older women. In addition, she said, younger women who had had biopsies showing a condition called atypical hyperplasia did seem to be at added risk and might be among the best candidates for taking the drugs. She said the data suggested that a five-year course of treatment could have protective effects that would continue even when the drugs were stopped.