Raloxifene for Breast Cancer Prevention: An NWHN (National Women's Health Network) Analysis April 18, 2006 On April 17, the National Cancer Institute (NCI) announced preliminary results from STAR, a large clinical trial comparing the effect of raloxifene and tamoxifen on risk of developing breast cancer in postmenopausal women who were considered to be at higher than average risk. The trial was funded by the NCI and Eli Lilly, manufacturer of raloxifene, which is currently marketed under the brand name Evista for prevention and treatment of osteoporosis. According to the NCI, both drugs cut the number of new cases of breast cancer in half, but women taking raloxifene experienced fewer serious side effects such as blood clots and cancer of the uterus. The NCI stressed this benefit in its announcement, stating “For many women, raloxifene’s benefits will outweigh its risks in a way that tamoxifen’s benefits do not.” NWHN is more cautious about the results of the trial, and believes that the breast cancer benefit of raloxifene may only be useful to a very small number of women. What do the numbers show? 19,747 women were part of STAR. They took either tamoxifen (brand name Nolvadex) or raloxifene, without knowing which medication they were being given, for up to five years. All of the women were postmenopausal, over half had already had hysterectomies and all were considered to be at higher than average risk of developing breast cancer. 163 women on tamoxifen and 167 women on raloxifene developed breast cancer during the trial. According to NCI, about 320 cases of breast cancer were expected in both groups if no drug treatment were taken. Both drugs led to a drop in breast cancer cases of roughly 50%, which is similar to the benefit found for tamoxifen when it was tested against a placebo in the P-1 trial. However, the earlier trial of tamoxifen showed that it caused a significant number of new problems for women, and researchers hoped that raloxifene would be a safer alternative. The numbers announced by NCI show that raloxifene is somewhat better than tamoxifen, although not strikingly so. 23 women taking raloxifene developed uterine cancer, compared with 36 women on tamoxifen; and 100 women taking raloxifene experienced serious blood clots, compared with 141 women on tamoxifen. NCI did not release estimates of the likelihood of these conditions in women not taking either drug, but earlier trials of tamoxifen showed that it tripled the risk of these conditions. The STAR trial shows that raloxifene is significantly less likely than tamoxifen to cause serious side effects – but we question whether it is likely to make a significant difference in women’s lives. Using the numbers released by NCI, we calculate that of the nearly 10,000 women who took raloxifene for up to five years, only about 30 benefited, once the serious risks are taken into account. While some women may appreciate this marginal benefit, the NWHN questions whether it should be viewed as a major advance in preventing breast cancer. Is this the final word on raloxifene and tamoxifen? Not by a long shot. NCI’s announcement doesn’t include much of the information that careful women and health care providers need to evaluate the overall risks and benefits of these drugs. We must also remember that the results have not yet been reviewed by experts who weren’t involved in the study (a requirement before the research can be published in a major medical journal), nor has the Food and Drug Administration (FDA) examined the records of the study to determine whether the agency will approve raloxifene for breast cancer risk reduction. What are some of the unanswered questions? We don’t know whether or not raloxifene, or tamoxifen for that matter, truly prevents breast cancer, or just delays it. NCI’s earlier trial of tamoxifen compared to a placebo only followed women for two years after they stopped taking their pills, not nearly long enough to know whether tamoxifen’s benefit is lasting. This trial can’t answer that question, either. Early results of this trial also suggest that raloxifene may affect the development of breast cancer in a different manner than tamoxifen. Tamoxifen reduces the likelihood of developing ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). The majority of women who develop these conditions will never develop invasive breast cancer, but some women with DCIS can progress to invasive breast cancer. In the STAR trial, raloxifene had no effect on the number of women who developed DCIS and LCIS. It's unclear what this means, and whether or not it is important. Many of the details of other benefits and risks of tamoxifen and raloxifene were not released by NCI. For example, we don’t know the specifics about how many women were able to avoid a bone fracture, how much both drugs increased the risk of stroke, and how many women died while they were part of the study. Should women take raloxifene? Women who are currently taking tamoxifen to reduce their risk of breast cancer should wait until the results of the STAR trial have been reviewed by the FDA before considering switching to raloxifene. FDA reviewers have access to all the information generated by the researchers and can provide an objective assessment of the results. Women who currently take bisphosphonates (drugs such as Fosamax, Actonel, Boniva) for osteoporosis also shouldn’t rush to switch. While there are still some questions about the long-term effects of bisphosphonates on bone structure, it seems clear that they do not increase the risk of stroke, blood clots or cancer. Healthy women who are not at higher than average risk of either breast cancer or osteoporosis should be especially skeptical of any efforts to persuade them to start taking raloxifene. NWHN believes it’s very likely that the ultimate results of the STAR trial will show that raloxifene isn’t quite as bad as tamoxifen, but it’s still not safe enough for most women to use. And we’ve learned that it’s important to wait until enough information is available for women to be able to make truly informed choices. In 1998, NCI announced the early results of the tamoxifen trial as a breakthrough in cancer prevention. Over a year later, the institute quietly published an article with the detailed risk benefit numbers and concluded that tamoxifen would harm more healthy women than it helped except for the very most high risk women. NWHN urges women and their health care providers not to get caught up in the hype, and wait for the facts. Ann's NOTE: This organization's actions were responsible for a closer examination of the unwanted ('side) effects from tamoxifen. They were the first to note some of the dangers. LINK to advocacy organization Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.