Breast Cancer Prevention Drug Outdone
The osteoporosis drug raloxifene is as effective as the drug now used to prevent breast cancer in high-risk post-menopausal women, but it has a much lower risk of producing life-threatening uterine cancer and blood clots, according to a new government study comparing the two drugs.
Tamoxifen is the current gold standard for preventing breast cancer in this group, but many women refuse to take it, and some physicians are reluctant to prescribe it, because of the dangers, which also include an increased risk of cataracts.
“There are a huge number of women that could benefit from [breast cancer] prevention that aren’t getting it ... because they don’t feel tamoxifen is the medicine for them,” said Dr. John Barstis of UCLA’s Jonsson Comprehensive Cancer Center. “This gives us a much better repertoire of medicines to offer patients.”
Raloxifene is also cheaper, about $75 per month compared with $100 for tamoxifen.
“It is clear that raloxifene is the winner of this trial,” said Dr. Norman Wolmark of the University of Pittsburgh Medical Center, who led the study released Monday.
Raloxifene has not been tested in pre-menopausal women at increased risk of breast cancer, and tamoxifen will remain the drug of choice for them. That group is much smaller, however. Most of the 212,000 American women who develop breast cancer each year are post-menopausal.
An estimated 40,000 American women die of the disease each year, making it the second-leading cause of cancer death after lung cancer.
Tamoxifen has been used for more than 30 years to treat breast cancer. A major study completed in 1998 demonstrated that it was also effective prophylactically, reducing risk by 50% in older women with increased risk of breast cancer, as calculated from such factors as a family history of the disease, age at first menses, age at first childbearing, age at menopause and the number of breast biopsies she had undergone.
It is now the only drug approved by the Food and Drug Administration for preventing breast cancer.
The 1998 study also showed that the drug worked like estrogen to preserve bone density, decreasing fractures of the hip, wrist and spine.
Raloxifene, manufactured by Eli Lilly & Co. and sold as Evista, is used by about half a million post-menopausal women to increase bone density. During trials of the drug for that purpose, researchers noticed a lowering of breast cancer risk and organized the current trial to compare it with tamoxifen.
The National Surgical Adjuvant Breast and Bowel Project, which conducted the study, enrolled 19,747 women, who were randomly assigned to receive one of the two drugs. The women had an average age of 58 and an average risk of 4% for developing breast cancer in a five-year period. In comparison, the five-year risk for the total population in that age range is 1.6%.
There were 163 cases of invasive breast cancer among the 9,726 women in the tamoxifen group, compared with 167 cases among the 9,745 women in the raloxifene group. That translates to about 17 cases for every 1,000 women, about half the number expected in women taking no drugs.
The risk of uterine cancer was 36% lower in the raloxifene group: 23 cases compared with 36.
Women taking raloxifene also had a nearly 30% lower risk of both pulmonary embolisms and deep-vein thromboses (life-threatening blood clots in a major vein), a 21% reduction in the number of cataracts and an 18% reduction in cataract surgery.
Both groups had about the same incidence of bone fractures and coronary disease, according to the study, to be presented this summer at a meeting of the American Society of Clinical Oncology.
The women taking raloxifene had a higher rate of both lobular carcinoma in situ, a benign condition usually left untreated, and ductal carcinoma in situ, in which the tumor can be treated with a simple lumpectomy. The breast cancers in situ are localized, as opposed to invasive, or metastasized, cancers.
The trial result “is good news for women,” said Dr. Leslie Ford of the National Cancer Institute, which sponsored the $88-million study. “For many women, raloxifene’s benefits will outweigh its risks in a way that tamoxifen’s benefits do not.”
An estimated 9 million post-menopausal women are at increased risk of developing breast cancer, according to Dr. Victor Vogel of the University of Pittsburgh. Because of tamoxifen’s risks, however, only about 2 million of them are good candidates for the drug. Because raloxifene has fewer risks, a larger number could benefit from taking it, but the researchers have not yet calculated how many.
The team now wants to test raloxifene against a family of drugs called aromatase inhibitors, which are already displacing tamoxifen in the treatment -- as opposed to prevention -- of breast cancer. Small studies have shown that the drugs can reduce a breast cancer patient’s risk of developing a tumor in her second breast as much as 80%.
The researchers now want to see whether the drugs are an effective preventive in women who do not have cancer and whether they have side effects similar to the drugs now in use. That trial should begin this year.
