Key Terms: Anticoagulant, Apoptosis, Double-blind study, Granulosa cells, Oncogene, Ovarian follicle.
Definition
Raloxifene is a synthetic called an antiestrogen. It mimics the action of estrogen on the bones, but blocks the effects of estrogen on breast and uterine tissues.
Purpose
Raloxifene is a hormone therapy drug that protects against bone loss (osteoporosis) in postmenopausal women. During large studies of raloxifene's effectiveness against osteoporosis, researchers discovered that women taking the drug developed fewer breast cancers than women taking the placebo. Therefore, it is being considered as a drug used to fight breast cancer.
Description
In 1997 the United States Food and Drug Administration (FDA) approved raloxifene for use against bone loss (osteoporosis) in postmenopausal women. As of 2001, raloxifene (Evista) was being tested as a hormone therapy drug to reduce the risk and fight breast cancer in postmenopausal women. As of 2003, raloxifene was only approved for use in postmenopausal women. However, studies were looking at its effects in preventing cancer in all women and in lowering risk of fractures in women with osteopenia.
Raloxifene belongs to a family of compounds called antiestrogens. Antiestrogens are used in cancer therapy to inhibit the effects of estrogen on target tissues. Estrogen is a steroid hormone secreted by granulosa cells of a maturing follicle within the female ovary. Depending on the target tissue, estrogen can stimulate the growth of female reproductive organs and breast tissue, play a role in the female menstrual cycle, and protect against bone loss by binding to estrogen receptors on the outside of cells within the target tissue. Antiestrogens act selectively against the effects of estrogen on target cells in a variety of ways, thus they are called selective estrogen receptor modulators (SERMs).
Raloxifene selectively inhibits the effects of estrogen on breast tissue and uterine tissue, while selectively mimicking the effects of estrogen on bone (by increasing bone mineral density). Its effects on breast and uterine tissue are thought to make raloxifene an excellent therapeutic agent against breast cancer and uterine cancer. Although researchers are unclear on exactly how raloxifene kills cancer cells, it is known to compete with estrogen by binding to estrogen receptors, therefore limiting the effects of estrogen on breast and uterine tissue. Raloxifene also may be involved in other anti-tumor activities affecting oncogene expression, promotion of apoptosis, and growth factor secretion.
In 2000 the STAR (Study of Tamoxifen and Raloxifene) study began. The purpose of this double-blind study was to evaluate the use of tamoxifen (another type of SERM) and raloxifene over a five year period in 22,000 postmenopausal women 35 years or older who are at high risk for developing breast cancer. The study will evaluate both the effectiveness and degree of side effects to determine which drug is most beneficial.
Recommended Dosage
Recommended dose for cancer treatment will emerge as clinical trials enter their final phases. Most studies, including the STAR trial, are using a total of 60 milligrams of raloxifene administered either once or twice (morning and night) each day with notable success. If a dosage is missed, patients should not double the next dosage. Instead, they should go back to their regular schedule and contact their doctor.
Precautions
Although raloxifene is only approved for use by women past the child bearing years, researchers emphasize that it is not recommended for women who are pregnant or breast feeding. In test animals, raloxifene caused birth defects and miscarriages. Although it is not known whether raloxifene is present in breast milk, it is possible that its presence may be toxic to infants. Further, this drug is not recommended for use in children.
Patients at risk for the formation of thromboembolisms should use raloxifene with caution. Raloxifene can cause a higher risk of developing blood clots. Additionally, women experiencing liver disease will have a higher level of raloxifene in their blood system.
Side Effects
Although raloxifene is usually well tolerated by patients, there are some side effects. Commonly reported side effects include mild nausea, vomiting, hot flashes, weight gain, bone pain, and hair thinning, which are not severe enough to stop therapy. Most of the side effect information regarding raloxifene comes from studies using it to counter osteoporosis where patients have not needed to take it over a long period of time. When studied for anticancer properties, raloxifene needs to be taken over a longer period of time. Since raloxifene's anticancer properties still are under investigation, researchers are not completely aware of all of the long term and potentially serious side effects. Researchers are aware that women taking raloxifene are three times more likely to develop thromboembolisms than women not taking raloxifene.
Interactions
The usefulness of raloxifene can be diminished if patients also are on estrogen supplements (such as Premarin, Estrace, Estratab, Climara, or Vivelle) and cholesterol-lowering cholestyramines (such as Questran). Cholestyramines decrease the absorption of raloxifene into the blood, while estrogen supplements increase the amount of estrogen competing with raloxifene for binding sites on target cells' estrogen receptors.
Raloxifene interferes with the anticoagulant effect of warfarin with severe consequences and even death. Patients using warfarin should make sure their physician is aware prior to commencing treatment with raloxifene.
Resources
Periodicals
Jancin, Bruce. "Breast Cancer Prevention Could be Next for Raloxifene." Family Practice News March 15, 2003: 32.
"Raloxifene Staunches the Risk for New Vertebral Fractures in Osteopenic Women." Women's Health Weekly November 20, 2003: 3.
—Sally C. McFarlane-Parrott; Teresa G. Odle
