Initial results from the Study of Tamoxifen and Raloxifene (STAR), one of the largest breast cancer prevention trials conducted to date, show that raloxifene is as effective as tamoxifen in preventing invasive breast cancer in postmenopausal, high-risk women, according to the US National Institutes of Health, which conducted the study.

STAR, one of the largest breast cancer prevention clinical trials ever conducted, enrolled 19,747 postmenopausal women at increased risk of the disease. Participants were randomly assigned to receive either 60 mg raloxifene or 20 mg tamoxifen daily for five years. Analysis was based on 19,471 women who had complete information available.

Both drugs reduced the risk of invasive breast cancer by about 50 percent. Among the 9,745 women in the raloxifene group, 167 developed invasive breast cancer compared with 163 of 9,726 women in the tamoxifen group.

While tamoxifen has been shown to halve the incidence of lobular carcinoma in situ and ductal carcinoma in situ, raloxifene did not have an effect on these diagnoses. Of the 9,726 women taking tamoxifen, 57 developed lobular or ductal cancer in situ compared to 81 of 9,745 taking raloxifene. This result confirms data reported in 2004 in a large study of raloxifene, the Continued Outcomes Relevant to Evista (or CORE Trial).

In terms of side effects, women who were randomized to raloxifene and who were followed for an average of about four years had 36 percent fewer uterine cancers and 29 percent fewer blood clots than women assigned to tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen.

The trial was coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals and was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health.

“This optimistic news from STAR is a significant step in breast cancer prevention,” said John E. Niederhuber, MD, currently providing leadership at NCI. “These results, once again, demonstrate the critical importance of clinical trials in our efforts to establish evidence-based practices.”

"In 1998, the landmark Breast Cancer Prevention Trial showed that tamoxifen could reduce the risk of invasive breast cancer in premenopausal and postmenopausal women by nearly 50 percent," said Norman Wolmark, MD, NSABP chairman. "Today, we can tell you that for postmenopausal women at increased risk of breast cancer, raloxifene is just as effective, without some of the serious side effects known to occur with tamoxifen."

There were equivalent numbers of strokes, myocardial infarctions, and bone fractures in the two patient groups. Both raloxifene and tamoxifen are known to protect bone health; it is estimated that half a million postmenopausal women are currently taking raloxifene to prevent or treat osteoporosis. Additionally, the initial results from STAR suggest that raloxifene does not increase the risk of developing a cataract, as tamoxifen does.

The STAR researchers also tracked known menopausal side effects that occur with both drugs and monitored the participants’ quality of life. The data show that side effects of both drugs were mild to moderate in severity, and quality of life was the same for both drugs.

Participants in STAR are now receiving information about which drug they were taking. Women assigned to raloxifene will continue to be provided with the drug until they have completed five years of treatment. Those women assigned to tamoxifen can choose to continue taking tamoxifen or to receive raloxifene to complete their five years of treatment.

Women who participated in STAR were postmenopausal, at least 35 years old, and had an increased risk of 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. Before participating in the study, the women were instructed about the potential risks and benefits of tamoxifen and raloxifene and then were asked to sign an informed consent document.

STAR investigators will present additional data at the 42nd annual meeting of the American Society for Clinical Oncology (ASCO) from June 2-6, 2006, in Atlanta, Ga. "This is an important and long awaited trial,” said Sandra J. Horning, MD, president of ASCO, “and we look forward to further discussion and analysis at the ASCO annual meeting that will address the observed differences in toxicity and prevention of non-invasive breast cancers with the two treatment approaches." A manuscript is also being submitted to a peer-reviewed journal for publication.