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A clinical trial found that the osteoporosis drug raloxifene (EVISTA) was comparable to taxmoxifen (NOLVADEX) in preventing breast cancer in postmenopausal women considered to be at higher-than-average risk of the disease.

However, consumers should wait until the FDA reviews and approves raloxifene for breast cancer prevention before rushing to use it.

Even before the study was published or presented at a medical meeting, the National Cancer Institute (NCI) announced the finding in an April 17 press release about the clinical trial, called the Study of Tamoxifen and Raloxifene (STAR). The full text of the NCI press release can be found on the Internet at http://www.cancer.gov/newscenter/pressreleases/STARresultsApr172006. Additional information about the trial is available at http://www.cancer.gov/newscenter/pressreleases/STARresultsQandA.

The STAR study enrolled 19,747 postmenopausal women who were at least 35 years old and had an increased risk of breast cancer as determined by their age, family history of breast cancer, personal medical history, age at first menstrual period, and age at the birth of their first live child. The average length of treatment with raloxifene or tamoxifen was almost four years.

The number of women experiencing invasive breast cancer in the groups receiving raloxifene and tamoxifen was statistically the same. There was a slightly lower percentage of women in the tamoxifen group who developed noninvasive breast cancer.

Women with a uterus who used raloxifene in the study were slightly less likely than women who used tamoxifen to develop uterine cancer, mainly endometrial cancer. But more than one-half of the women in the study had a hysterectomy and were therefore not at risk of developing uterine cancer.

There were also slightly fewer deep vein thromboses (blood clots in a major veins) and pulmonary embolisms (blood clots in the lung caused by blood clots in major veins breaking off) in women receiving raloxifene compared to women in tamoxifen group.

Statistically, there was no difference between the numbers of women who suffered a stroke in the raloxifene versus the tamoxifen groups. Women at an increased risk of stroke, those with uncontrolled hypertension or uncontrolled diabetes, or a history of stroke, transient ischemic attack, or atrial fibrillation (a type of heart rhythm disturbance,) were not eligible to participate in the STAR trial.

The table accompanying this article compares the preliminary results of tamoxifen and raloxifene in the STAR trial.

Looking at the numbers in the table in a different way, in about 2 in 100 women taking raloxifene or tamoxifen for four years, a new case of invasive breast cancer will be detected. The difference in the percentage of women detected as having non-invasive breast cancer was 1/4 percent in favor of tamoxifen. This translates to a difference of less than 3 in 1000 women.  

In women with an intact uterus, there was a difference in uterine cancers of about 3 in 1000 women favoring raloxifene. The differences between the number of women having a blood clot in a vein or a blood clot that travels to the lung for raloxifene and tamoxifen is about 2 in 1000 women. The number of strokes in the raloxifene and tamoxifen groups is essentially the same.

Raloxifene was approved by the Food and Drug Administration (FDA) in December 1997 for the treatment and prevention of osteoporosis in postmenopausal women with supplemental calcium and vitamin D to the diet if daily intake is inadequate. It belongs to the family of drugs known as selective estrogen receptor modulators (SERMs), which act like estrogen in bone and some other tissues but block the effects of estrogen in reproductive tissues.

Raloxifene has become a top seller for its manufacturer, Eli Lilly and Co. of Indianapolis, IN. In 2005, more than 5.2 million raloxifene prescriptions were dispensed. Sales of raloxifene exceeded $500 million.

Data from the STAR trial must be scrutinized and then approved by the FDA before any legal claims can be made by Eli Lilly about a benefit, if any, for raloxifene in breast cancer. Currently, the FDA-approved professional product label for raloxifene says, “[t]he effectiveness of raloxifene in reducing the risk of breast cancer has not been established.”  

Eli Lilly has already tried to illegally market raloxifene as a breast cancer treatment. The FDA found that Eli Lilly was violating federal law by illegally promoting raloxifene for breast cancer prevention when it was only approved for osteoporosis. The agency sent a warning letter to Lilly in January 1999 telling the company to stop the illegal ads.  

A press release dated December 11, 1998 stated “. . . Evista (raloxifene hydrochloride), Eli Lilly and Company’s osteoporosis drug, reduces the incidence of newly-diagnosed invasive breast cancer, potentially the most serious type of breast cancer, by 63 percent among postmenopausal women taking the therapy for more than three years.” The press release also makes the broad claim that “. . . Evista has a significant, positive impact on a woman’s health after menopause” and that “This is a significant breakthrough in women’s health.” Lilly states that the reduction in the risk of breast cancer is the direct result of new scientific findings from osteoporosis studies in postmenopausal women (see Worst Pills, Best Pills News March 1999).

Lilly was also caught violating the law for false and misleading direct-to-consumer ads that appeared in the September 1998 issue of Healthmagazine and the October 1998 issue of Prevention magazine. These advertisements overstated raloxifene’s benefits by stating that it “[p]revents osteoporosis ... Lowers cholesterol ... Addresses concerns about breast cancer,” which implies that the drug is FDA-approved for a broader range of uses than is actually the case. These ads also made unsubstantiated safety claims by saying the drug addressed concerns about breast cancer and “[i]mportantly, women taking Evista had no increased risk of breast or uterine cancer in studies of up to 3 years.”  

Eli Lilly also minimized the risk of blood clots, a serious adverse effect of the drug, by saying “... the chance of getting them from taking Evista is rare....”    

The Medical Letter on Drugs and Therapeutics, a highly respected source of independent drug information written for physicians and pharmacists, reviewed the limited data available in the NCI press release regarding the STAR trial in its May 8, 2006 issue and concluded:

“It is not clear how the lower incidence of uterine cancer with raloxifene equates with the lower incidence of non-invasive breast cancer with tamoxifen. Longer studies to evaluate mortality are needed. No data are available on the efficacy or risk, if any, of switching from tamoxifen to raloxifene.”

Is raloxifene a breakthrough in reducing the incidence of breast cancer in women who are at a high risk for the disease? No one knows yet, but probably not.

The STAR study has not been published and the data have not been reviewed and approved by the FDA. If the numbers from the preliminary STAR results stand up to rigorous review, the differences between the raloxifene and tamoxifen are small. At this time, we agree with the editors of the Medical Letter: The relative efficacy of raloxifene is not clear.  

What You Can Do

You should wait to use raloxifene for reducing the risk of breast cancer until the drug is FDA approved for this use.

A clinical trial found that the osteoporosis drug raloxifene (EVISTA) was comparable to taxmoxifen (NOLVADEX) in preventing breast cancer in postmenopausal women considered to be at higher-than-average risk of the disease.

However, consumers should wait until the FDA reviews and approves raloxifene for breast cancer prevention before rushing to use it.

Even before the study was published or presented at a medical meeting, the National Cancer Institute (NCI) announced the finding in an April 17 press release about the clinical trial, called the Study of Tamoxifen and Raloxifene (STAR). The full text of the NCI press release can be found on the Internet at http://www.cancer.gov/newscenter/pressreleases/STARresultsApr172006. Additional information about the trial is available at http://www.cancer.gov/newscenter/pressreleases/STARresultsQandA.

The STAR study enrolled 19,747 postmenopausal women who were at least 35 years old and had an increased risk of breast cancer as determined by their age, family history of breast cancer, personal medical history, age at first menstrual period, and age at the birth of their first live child. The average length of treatment with raloxifene or tamoxifen was almost four years.

The number of women experiencing invasive breast cancer in the groups receiving raloxifene and tamoxifen was statistically the same. There was a slightly lower percentage of women in the tamoxifen group who developed noninvasive breast cancer.

Women with a uterus who used raloxifene in the study were slightly less likely than women who used tamoxifen to develop uterine cancer, mainly endometrial cancer. But more than one-half of the women in the study had a hysterectomy and were therefore not at risk of developing uterine cancer.

There were also slightly fewer deep vein thromboses (blood clots in a major veins) and pulmonary embolisms (blood clots in the lung caused by blood clots in major veins breaking off) in women receiving raloxifene compared to women in tamoxifen group.

Statistically, there was no difference between the numbers of women who suffered a stroke in the raloxifene versus the tamoxifen groups. Women at an increased risk of stroke, those with uncontrolled hypertension or uncontrolled diabetes, or a history of stroke, transient ischemic attack, or atrial fibrillation (a type of heart rhythm disturbance,) were not eligible to participate in the STAR trial.

The table accompanying this article compares the preliminary results of tamoxifen and raloxifene in the STAR trial.

Looking at the numbers in the table in a different way, in about 2 in 100 women taking raloxifene or tamoxifen for four years, a new case of invasive breast cancer will be detected. The difference in the percentage of women detected as having non-invasive breast cancer was 1/4 percent in favor of tamoxifen. This translates to a difference of less than 3 in 1000 women.  

In women with an intact uterus, there was a difference in uterine cancers of about 3 in 1000 women favoring raloxifene. The differences between the number of women having a blood clot in a vein or a blood clot that travels to the lung for raloxifene and tamoxifen is about 2 in 1000 women. The number of strokes in the raloxifene and tamoxifen groups is essentially the same.

Raloxifene was approved by the Food and Drug Administration (FDA) in December 1997 for the treatment and prevention of osteoporosis in postmenopausal women with supplemental calcium and vitamin D to the diet if daily intake is inadequate. It belongs to the family of drugs known as selective estrogen receptor modulators (SERMs), which act like estrogen in bone and some other tissues but block the effects of estrogen in reproductive tissues.

Raloxifene has become a top seller for its manufacturer, Eli Lilly and Co. of Indianapolis, IN. In 2005, more than 5.2 million raloxifene prescriptions were dispensed. Sales of raloxifene exceeded $500 million.

Data from the STAR trial must be scrutinized and then approved by the FDA before any legal claims can be made by Eli Lilly about a benefit, if any, for raloxifene in breast cancer. Currently, the FDA-approved professional product label for raloxifene says, “[t]he effectiveness of raloxifene in reducing the risk of breast cancer has not been established.”  

Eli Lilly has already tried to illegally market raloxifene as a breast cancer treatment. The FDA found that Eli Lilly was violating federal law by illegally promoting raloxifene for breast cancer prevention when it was only approved for osteoporosis. The agency sent a warning letter to Lilly in January 1999 telling the company to stop the illegal ads.  

A press release dated December 11, 1998 stated “. . . Evista (raloxifene hydrochloride), Eli Lilly and Company’s osteoporosis drug, reduces the incidence of newly-diagnosed invasive breast cancer, potentially the most serious type of breast cancer, by 63 percent among postmenopausal women taking the therapy for more than three years.” The press release also makes the broad claim that “. . . Evista has a significant, positive impact on a woman’s health after menopause” and that “This is a significant breakthrough in women’s health.” Lilly states that the reduction in the risk of breast cancer is the direct result of new scientific findings from osteoporosis studies in postmenopausal women (see Worst Pills, Best Pills News March 1999).

Lilly was also caught violating the law for false and misleading direct-to-consumer ads that appeared in the September 1998 issue of Healthmagazine and the October 1998 issue of Prevention magazine. These advertisements overstated raloxifene’s benefits by stating that it “[p]revents osteoporosis ... Lowers cholesterol ... Addresses concerns about breast cancer,” which implies that the drug is FDA-approved for a broader range of uses than is actually the case. These ads also made unsubstantiated safety claims by saying the drug addressed concerns about breast cancer and “[i]mportantly, women taking Evista had no increased risk of breast or uterine cancer in studies of up to 3 years.”  

Eli Lilly also minimized the risk of blood clots, a serious adverse effect of the drug, by saying “... the chance of getting them from taking Evista is rare....”    

The Medical Letter on Drugs and Therapeutics, a highly respected source of independent drug information written for physicians and pharmacists, reviewed the limited data available in the NCI press release regarding the STAR trial in its May 8, 2006 issue and concluded:

“It is not clear how the lower incidence of uterine cancer with raloxifene equates with the lower incidence of non-invasive breast cancer with tamoxifen. Longer studies to evaluate mortality are needed. No data are available on the efficacy or risk, if any, of switching from tamoxifen to raloxifene.”

Is raloxifene a breakthrough in reducing the incidence of breast cancer in women who are at a high risk for the disease? No one knows yet, but probably not.

The STAR study has not been published and the data have not been reviewed and approved by the FDA. If the numbers from the preliminary STAR results stand up to rigorous review, the differences between the raloxifene and tamoxifen are small. At this time, we agree with the editors of the Medical Letter: The relative efficacy of raloxifene is not clear.  

What You Can Do

You should wait to use raloxifene for reducing the risk of breast cancer until the drug is FDA approved for this use.