The drug in question is raloxifene, sold under the brand name Evista. Some people with thinning bones (including those with osteoporosis, as well as some of those diagnosed with osteopenia, a lesser degree of bone loss) take this drug to slow down the destruction of mature bone by the body. As we get older, the cells that build new bone (called osteoblasts) stop working as efficiently as the cells that eat up old bone (called osteoclasts). The theory is that by slowing down the osteoclasts, patients will have thicker bones that are less susceptible to fracture. Evista has sold well. But it’s not nearly as popular as another bone-sparing drug, Fosamax (alendronate), which has often been doctors’ first choice because there’s more evidence that it prevents fractures.
Now, however, two recent studies have some wondering if Evista might be a better choice. In the first—the Study on Tamoxifen and Raloxifene (STAR)—researchers wanted to determine if there was a better alternative to tamoxifen, a medication that can lower a woman’s risk of developing breast cancer as well as reduce the chance of recurrence in breast cancer survivors.
Tamoxifen is part of a class of drugs called SERMs, which stands for selective estrogen receptor modulators. In simple terms, that means that SERMS act like the hormone estrogen in some parts of the body, but not in others. In tamoxifen’s case, it acts like estrogen in the bones (by making them stronger) but not in the breast, where estrogen can encourage the proliferation of cancer cells. The problem is that tamoxifen can have a dark side. It acts like an estrogen in the uterus and can encourage overgrowth of the uterine lining (also known as the endometrium.) This can increase a woman’s risk of developing endometrial cancer. Women taking tamoxifen have not been thrilled to learn that the drug they’re taking to reduce their chance of getting one kind of cancer may slightly increase their risk of developing a different kind of cancer. So researchers have been looking for other options.
It didn’t take long for them to set their sites on raloxifene, which is also a SERM and shares many of tamoxifen’s positive traits: it protects high-risk women against breast cancer and keeps bones denser. But early studies also indicated that there was a key difference: raloxifene didn’t seem to increase the risk of endometrial cancer.
For the STAR study, 19,747 postmenopausal women (average age 58.5 years) at increased risk of breast cancer were randomly assigned to take either tamoxifene or raloxifene. Five years later, researchers were able to confirm that those taking raloxifene developed fewer cases of endometrial cancer than those taking tamoxifen. Raloxifene also reduced the risk of invasive breast cancer to the same extent as did tamoxifen.That was good news. But they also found that raloxifene didn’t seem to protect against noninvasive types of breast cancer as well as tamoxifen. As a result, doctors who work with breast cancer survivors say it’s not clear that one is truly superior to the other.
Nonetheless, all the publicity surrounding the STAR results had many women who were on Fosamax wondering if they should be taking Evista (raloxifene) instead because it protects bones and breasts, and maybe even their hearts too. (Raloxifene, like tamoxifen, lowers total cholesterol). The cardiac benefit became less clear soon after, though, when findings from another study—the Raloxifene Use for the Heart (RUTH) study—appeared in the New England Journal of Medicine. RUTH researchers had hoped that a daily dose of raloxifene might protect women with coronary heart disease from future heart attacks and reduce their risk of dying of the disease. To test this idea, they got 10,101 postmenopausal women with a history of heart disease from 26 countries (average age 67.5) to volunteer to be randomly assigned to take either 60 mg of raloxifene a day or a placebo and followed the women for an average of five and a half years. They found that raloxifene did not reduce the women’s risk of future heart attacks. Worse, it increased the chance that they would have a fatal stroke or develop a blood clot (which can also happen with tamoxifen).
That news gave some of raloxifene’s new fans pause. After all, it’s one thing to take a drug that seems to have next-to-no side effects to prevent a serious disease. It’s another thing to take a drug that increases your risk of serious conditions like stroke and blood clots in order to protect yourself from diseases like breast cancer or osteoporosis that you don’t have and may never get. “I think women are justifiably concerned about the side effects,” says Dr. John P. Bilezikian, director of the metabolic bone diseases program at NewYork-Presbyterian Hospital/Columbia University Medical Center. “You have to make a risk-benefit analysis in these kinds of situations. If there was a woman who was at high risk for breast cancer but also at high risk for blood clots, for example, I would be reluctant to use Evista.”
Evista also has another downside. “It can cause hot flashes to become significantly worse,” adds Rosen. “As a result, some of the younger women [those in their 40s and 50s who are taking bone remodelers] can’t tolerate it very well.”
Still, while Evista isn’t for everyone, researchers say there are women who may be better off switching. A lot depends on which disease a woman is most concerned about. “I would think about switching a patient if she was at high risk for breast cancer,” says Bilezikian. “But if she was also at very high risk for fracture, I might not be so enthusiastic. Even though Evista is a very good drug, there are no clinical trials that show that it’s globally effective against all fractures in the way Fosamax is globally effective.” For example, while Evista protects against fractures of the back bones, there is no evidence that it reduces the likelihood of hip fracture. Bilezikian says that if he had a patient with very low bone density of the hip and switched her from Fosamax to Evista, he would worry that she wasn’t as well protected.
And finally, what about breast cancer survivors? Many currently take tamoxifen to prevent recurrence of breast cancer. But studies indicate that after five years, tamoxifen stops protecting against a return of cancer and might even act as a stimulant, says Dr. Charles Loprinzi, a Mayo Clinic oncologist. After five years on tamoxifen, could these women switch to raloxifene and continue to be protected against both breast cancer and osteoporosis? No studies answer that question, but Loprinzi says specialists “would be wary” of using it, since the two SERMS are so similar. The possible exception, he says, would be women who never took tamoxifen because their cancers weren’t responsive to the hormone estrogen (otherwise known as estrogen receptor-negative breast cancer.) They could take it to protect against future development of estrogen receptor-positive breast cancer, and to protect their bones.
If thinning bones are a problem for you, talk to your doctor about your medical history. Together, you can determine which drug (if either) would work best for you. But for women who are at high risk for breast cancer and at high risk for osteoporosis, raloxifene may come as close to a two-fer as modern medicine has to offer.
