The STAR Trial: Study of Tamoxifen and Raloxifene (STAR) Clinical Trial
- The STAR Trial
- Prior Research on Breast Cancer Prevention
- About Tamoxifen and Raloxifene
- Additional STAR Trial Information and References
The National Surgical Adjuvant Breast and Bowel Project (NSABP) is leading the STAR clinical trialone of the largest trials of on breast cancer prevention ever undertaken. STAR, or Study of Tamoxifen and Raloxifene, is investigating whether the drugs tamoxifen (brand name, Nolvadex) and raloxifene (Evista), help prevent breast cancer in women at high risk for disease. In 2007, initial results of STAR and other clinical trials led to the FDA's approval of raloxifene to help prevent invasive breast cancer in post-menopausal women at high risk of the disease. High risk women include those with a strong family history of the disease, history (and results) of breast biopsies, age when a women began menstruating, and other factors. The final results of the STAR trial will help provide more insight on breast cancer prevention.
Recruitment for the STAR trial is now closed and researchers are evaluating data. The STAR trial recruited volunteers from more than 400 centers across the United States, Puerto Rico, and Canada. In all, researchers enrolled more than 19,000 post-menopausal women of all races at increased risk of breast cancer. In addition to determining if tamoxifen and raloxifene can prevent breast cancer, the study is also investigating whether there are additional benefits of raloxifene versus tamoxifen.
According to the NSABP, STAR is the first trial to compare a drug proven to reduce the chance of developing breast cancer with another drug that has the potential to reduce breast cancer risk. All participants received either tamoxifen or raloxifene and took the drug for five years. No patients received a placebo, or inactive pill.
Significant efforts were made to select qualified centers in as many geographical areas as possible so that STAR was accessible to a large number of women seeking a possible breast cancer prevention option. The STAR centers are located at major medical centers and university hospitals, at community hospitals, health maintenance organizations, Community Clinical Oncology Programs (CCOPs), and in physician practice groups. Click here to go to the NSABP website to see a list of centers participating in the trial.
The STAR study is supported by the National Cancer Institute (NCI), Eli Lilly and Company (who markets Evista/raloxifene for the treatment of osteoporosis), and Zeneca Pharmaceuticals.
The May 1999 opening of the Study of Tamoxifen and Raloxifene (STAR) trial followed closely on the heels of the NSABP's first breast cancer prevention trial, in which researchers found that women at high risk of breast cancer who took tamoxifen experienced a 49% decrease in the incidence of invasive breast cancer compared to those who did not receive the drug and received a placebo (inactive pill) instead. The study showed that women taking tamoxifen also had fewer diagnoses of non-invasive breast cancer, such as ductal carcinoma in situ (DCIS).
The original breast cancer prevention clinical trial ran from April 1992 to1998 (women had been participating in the trial for approximately four years). The 13,388 women who participated in the breast cancer prevention trial were selected by chance to receive either tamoxifen or a placebo. The study was double-blinded in that 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 breast cancer prevention trial also aimed to determine whether tamoxifen decreased the number of heart attacks and reduced the number of bone fractures in these women. The results of the first breast cancer prevention 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.Click here for more information on these study results.
Both tamoxifen and raloxifene are "anti-estrogens." Anti-estrogens work by competing with estrogen to bind to estrogen receptors in breast cancer cells. By blocking estrogen in the breast, tamoxifen and raloxifene may slow the growth and reproduction of breast cancer cells.
While tamoxifen and raloxifene may fight estrogen in breast cancer cells, they 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). Raloxifene is commonly prescribed help prevent and treat osteoporosis. It has been shown to help build new bone and reduce the risk of fractures.
Raloxifene was approved in December 1997 by the FDA to prevent osteoporosis. In 2007, based on initial results of STAR and other clinical trials, the FDA approved raloxifene to reduce the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Tamoxifen has been approved by the FDA to treat women with breast cancer for more than two decades.
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 also increases 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 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
Raloxifene can cause serious side effects including blood clots in the legs and lungs, and death due to stroke. Women with current or prior blood clots in the legs, lungs, or eyes should not take Evista. Other potential side effects include:
- hot flashes
- leg cramps
- swelling of the legs and feet
- flu-like symptoms
- joint pain
The FDA cautions that raloxifene should not be taken by pre-menopausal women and women who are or may become pregnant because it may cause harm to the unborn baby. In addition, ralxofene should not be taken with cholestyramine (a drug used to lower cholesterol levels) or estrogens.
- For information on the National Adjuvant Breast and Bowel Project (NSABP), please visit http://www.imaginis.com/breasthealth/star/nsabp_info.asp
- For NSABP information on STAR and how to enroll, please visit http://www.nsabp.pitt.edu/
- To learn more about tamoxifen, please visit http://www.imaginis.com/breasthealth/tamoxifen.asp
- For NSABP information on STAR, please visit http://www.nsabp.pitt.edu/
- To learn more about raloxifene, please visit http://www.imaginis.com/osteoporosis/osteo_treatment.asp#raloxifene
- The April 30, 2006 Imaginis.com article, "Osteoporosis Drug, Raloxifene, Shows Promise in Preventing Breast Cancer," is available at http://www.imaginis.com/breasthealth/news/news4.30.06.asp
Updated: November 12, 2007