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Vol. 05 Issue 4, Late Fall 2000

Commentary on STAR
The Ribbon 

Meghan B. Brennan, RN, MSN, OCN
Michael P. Osborne, MD, FRCS, FACS
Strang Cancer Prevention Center

The "Study of Tamoxifen and Raloxifene (STAR) in Postmenopausal Women at Increased Risk for Invasive Breast Cancer" (P-2) is a clinical trial currently being conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). This large, multi-center trial is the first North American trial to compare two different pharmaceuticals, tamoxifen and raloxifene, as preventive agents for breast cancer. Tamoxifen, in the NSABPÕs Breast Cancer Prevention Trial (P-1), demonstrated a decrease in the incidence of breast cancer by about 50% in patients at increased risk for developing the disease (Fisher et al., 1998). An early clinical trial of raloxifene to evaluate its efficacy in preventing osteoporosis, the Multiple Outcomes of Raloxifene Evaluation (MORE), suggested that raloxifene may also decrease the incidence of breast cancer (Cummings et al., 1999). The STAR trial compares the effectiveness of these two drugs at decreasing the incidence of breast cancer as well as compares their associated side effects.

As expected from the NSABP, the STAR trial is well designed. It is a large, prospective, double-blinded, randomized trial involving approximately 23,000 women that will provide important information concerning raloxifene. Although the study design is well planned, there are some areas of concern. The STAR trial will not provide data on breast cancer associated mortality of the patients in the study (Osborne, 1999). Initially, the P-1 trial had patients in a placebo control group; but these patients were allowed to cross to tamoxifen when the results were published (Fisher et al., 1998). Because of the cross over there will be no control group to compare breast cancer mortality data. It will be difficult to establish a difference in mortality of patients taking tamoxifen, raloxifene or no drug. The use of historical controls is not appropriate as they may have different eligibility parameters compared to the STAR trial making it difficult to extrapolate data to patients on the STAR trial. Moreover, like most clinical trials, this data will not be available for many years (Osborne, 1999).

One of the criticisms of the tamoxifen prevention trial is whether patients are actually receiving treatment for an early, undetected breast cancer. It is postulated that some patients in the P-1 had early breast cancers that were not detected on mammography or physical exam. This means that some of the patients who developed breast cancer may not represent those at increased risk and did not have the disease. For the patients on tamoxifen, the drug would actually treat the cancer, potentially delaying its manifestation. However, for the patients on placebo, these cancers would continue to grow until detectable. This may account for the increased incidence of breast cancer in the placebo group as opposed to the tamoxifen group. The placebo data may have merely represented patients with early undetectable cancer that did not receive treatment. This may also be true for the STAR trial; tamoxifen is an agent that is proven to treat cancer, while raloxifene has never been tested or proven as such. However, intuitively it would seem likely that raloxifene will be equally effective as tamoxifen.

Additionally, it has consistently been a challenge to incorporate minority populations into research trials within the United States, as seen in the P-1 trial. The efforts put forth to incorporate minorities into the NSABP treatment and prevention trials are to be applauded. The directors of the STAR trial have gone out into the community and attempted to bring the prevention trial to the minority populations. The challenge is not only reaching the different populations, but also assisting them in understanding the benefit-risk ratio in relation to them. In the past the comparable side effects of tamoxifen in other settings made it reasonable to apply the same criteria for tamoxifen use in all ethnic groups. Whether or not this will hold true with raloxifene is unknown. The experience with raloxifene is still rather limited in comparison (Cheblowski, et al., 1999).

Summary. The STAR trial will help to answer an important question related to breast cancer prevention. However, this trial is not without limitations. There is little information related to breast cancer mortality in this group of high-risk women. The use of a preventive agent may decrease the amount of breast cancer, however the number of patients that die from breast cancer may not be significantly different. Because the biology of breast cancer is still not completely understood, it is unknown if this prevention trial is actually treating occult breast cancers not yet detectable. Again, the hurdle with incorporating minorities in prevention clinical trials remains. Minorities are consistently underrepresented in clinical trials and incorporating them poses a challenge for the directors of the STAR trial. In addition, this trial specifically targets postmenopausal women who do not have breast cancer, but are at increased risk for developing it. The use of raloxifene to treat patients with breast cancer or a history of breast cancer is unproven. The information gained from this trial should not be interpreted and used to treat patients with breast cancer. Furthermore, the use of raloxifene as a preventive agent for breast cancer is unproven. Patients should not receive raloxifene as a preventive agent for breast cancer unless they are on a clinical trial (Cheblowski, et al., 1999).

References

Fisher B., J.P. Constatino, D.L. Wickerham, et al. "Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study." J Nat Can Inst, 90 (18) (1998): 1371-1388.

Cummings S.R., S. Eckert, K.A. Kruefer, et al: "The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE randomized trial." JAMA, (1999) 281: 2189-2197.

Osborne M.P. "Chemoprevention of breast cancer." Surg Clin North Am, 79(5) (1999): 1207-1221.

Osborne M.P. "Breast cancer prevention by antiestrogens." Ann NY Acad Sci, (1999) 889: 146-51.

Cheblowski R.T., D.E. Collyar, M.R. Somerfield, et al. "American Society of Clinical Oncology technology assessment on breast cancer risk reduction strategies: Tamoxifen and raloxifene." J Clin Oncol, 17(6) (1999):1939-1955.

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Last Update 01.2.01