Study of Tamoxifen and Raloxifene (STAR)

The National Surgical Adjuvant Breast and Bowel Project (NSABP) has selected  NewYork-Presbyterian Hospital-Columbia campus to participate in its second major Breast Cancer Prevention Trial (BCPT).  The May 25, 1999, opening of the Study of Tamoxifen and Raloxifene (STAR) trial follows closely on the heels of the NSABP's first breast cancer prevention trial.  In the first BCPT study, researchers found women at increased risk for the disease had a 49% decrease in the incidence of invasive breast cancer who took tamoxifen compared to those who received a placebo. The study showed that women taking tamoxifen also had fewer diagnoses of noninvasive breast cancer, such as ductal carcinoma in situ (DCIS).

The original BCPT clinical trial ran from April 1992 to 1998. The 13,388 women who participated in the BCPT were randomized (selected by chance) to receive either tamoxifen or a placebo (an inactive pill). The BCPT was a double-blind study, neither the participant nor her physician knew which pill she was receiving. Double-blind studies allow researchers to clearly see what the true benefits and side effects of a drug or treatment may be without the influence of other factors. The BCPT also aimed to determine whether taking tamoxifen decreased the number of heart attacks and reduced the number of bone fractures in these women. The results of the first BCPT trial revealed that women in the tamoxifen group had fewer hip, wrist, and spine fractures than women in the placebo group. There was no difference in the number of heart attacks between the two groups.

The STAR trial will be one of the largest breast cancer prevention studies ever. Researchers plan to study 22,000 postmenopausal women at increased risk of breast cancer to determine whether the osteoporosis prevention drug raloxifene (Evista) is as effective in the prevention of developing breast cancer as tamoxifen (Nolvadex).   The study will also investigate whether there are additional benefits of raloxifene versus tamoxifen. Since enrollment began in May 1999, over 6,000 women have been participating in the STAR trial. Researchers hope to enroll another 16,000 women within the next two to three years.

The new STAR clinical trial is examining whether raloxifene, a drug similar to tamoxifen, is also effective in preventing invasive breast cancer in women who have not had the disease and whether it offers any benefits over those obtained with tamoxifen.  STAR is a randomized, double blind study that will include 22,000 postmenopausal women 35 or older who are at increased risk for developing breast cancer as determined by their age, family history of breast cancer, personal medical history, age at first menstrual period, and age at first live birth.

Candidates go through a process known as informed consent, during which they learn about the potential benefits and risks of tamoxifen and raloxifene before deciding whether to participate in STAR.  The women who enroll will be randomly assigned to a regimen of 20 mg of tamoxifen or 60 mg of raloxifene daily for five years. They will receive close follow-up examinations, including mammography, physical exam, and gynecologic exam on a regular basis for at least seven years. Women who participate in STAR will not be charged for the cost of either tamoxifen or raloxifene.

To grow and reproduce, breast cancer cells require the female hormone estrogen. Tamoxifen and raloxifene are "anti-estrogens" and work by competing with estrogen to bind to estrogen receptors in breast cells. By blocking estrogen effects in the breast, tamoxifen and raloxifene slow the growth and reproduction of breast cancer cells.

Tamoxifen and raloxifene also mimic the positive effects of estrogen in other body systems. Post-menopausal women who take tamoxifen may decrease their risk of heart disease or osteoporosis (a degenerative bone disease) without having to use hormone replacement therapy (HRT).

As with all drug treatments, the side effects of tamoxifen and raloxifene vary from individual to individual. The most common side effect of tamoxifen and raloxifene is a higher occurrence of hot flashes. Other side effects of tamoxifen include irregular menstrual cycles, unusual vaginal discharge or bleeding, and irritation of skin around the vagina. Tamoxifen does not cause menopause in pre-menopausal women, though its side effects may mimic menopausal symptoms. For most young women who take tamoxifen, the ovaries continue to act normally and produce estrogen in the same or slightly increased amounts. In fact, some studies have suggested that tamoxifen may make pre-menopausal women more fertile.

Side effects of tamoxifen include:

• Hot flashes
• Irregular menstrual cycles
• Unusual vaginal discharge or bleeding
• Irritation of skin around vagina

Tamoxifen can also increase a woman's chances of developing serious health problems including:

• endometrial cancer (cancer of the lining of the uterus)
• deep vein thrombosis (blood clots in large veins, particularly in the legs)
• pulmonary embolism (blood clot in the lung)
• possibly stroke

Because endometrial cancer is a potential side effect of tamoxifen, women with uterine problems are not usually candidates for tamoxifen treatment. In addition, pregnant women should not use tamoxifen because animal studies reveal that the drug may cause serious harm to the growing fetus. Women with a personal history of severe blood clotting or cataracts should also avoid tamoxifen.

Women should not take tamoxifen if:

• they are pregnant
• have a history of uterine problems
• have a history of blood clots
• have a history of cataracts

Women taking raloxifene in osteoporosis studies have been shown to have an increased chance of developing deep vein thrombosis or pulmonary embolism (similar to the risk seen with tamoxifen). In these studies, raloxifene did not increase the risk of endometrial cancer. An important part of STAR will be to compare the long-term safety of raloxifene and tamoxifen in women at increased risk for breast cancer.

Raloxifene was approved in December 1997 by the FDA to prevent osteoporosis and has been in clinical trials for over five years. Tamoxifen has been approved by the FDA to treat women with breast cancer for more than 20 years and has been in clinical trials for about 30 years. Raloxifene (Evista) is currently FDA approved only for use in preventing/treating osteoporosis in post-menopausal women.

If you are postmenopausal, female, and have no history of cancer and would like to know your potential risk of getting breast cancer over the next 5 years, you may call the Herbert Irving Comprehensive Cancer Center at 212 305-3917. 

Women who are postmenopausal and have an elevated risk of breast cancer may be eligible for the STAR trial.  This is an NCI supported study and both tamoxifen and raloxifene will be offered at no charge to study participants.