Researchers release results of (STAR) breast cancer prevention trial

October 01, 2015

"For years, doctors have offered tamoxifen to women at increased risk for breast cancer, after studies showed it could result in a nearly 50 percent reduction in invasive breast cancers in these women. At the same time, we also know tamoxifen has had side effects that have impacted the willingness of women and their physicians to use it. As a result many fewer women than anticipated have taken advantage of tamoxifen as a prevention option. We've been eagerly awaiting the results of the STAR trial, which was designed to compare the effectiveness of tamoxifen to another drug, raloxifene, which like tamoxifen blocks the effect of estrogen on breast tissue. The results released today show raloxifene is as effective as tamoxifen at reducing the risk of invasive breast cancer, with a better safety profile.

"But there's an important caveat. It is clear from this and previous studies that tamoxifen is also effective in reducing the risk of two important, non-invasive cancers: lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). The current trial shows raloxifene does not have this same benefit, meaning taking away the risk of increased uterine cancer and blood clots from tamoxifen comes at a price: the loss of the protective effect of tamoxifen to potentially prevent these non-invasive breast cancers. As a result, the outcome of the study is not as clear cut as we might have hoped for. It will take some time for experts to review the data to determine which of the two treatments is preferable.

"For now it will be very important for women an increased risk of breast cancer to make an informed decision with the advice of their physician as to which approach is best for them."

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STAR enrolled 19,747 women. This data analysis is based on the 19,471 women for whom complete study information was available. The numbers of invasive breast cancers in both groups of women were statistically equivalent. Among the 9,745 women in the raloxifene group, 167 developed invasive breast cancer, compared to 163 of 9,726 women in the tamoxifen group. More than half of the women who joined STAR had had a hysterectomy and, therefore, were not at risk of uterine cancer. For those women with a uterus, 36 of 4,732 who were assigned to take tamoxifen developed uterine cancers (mainly endometrial cancer) compared to 23 of 4,712 women who were assigned to take raloxifene. In STAR, women in the raloxifene group had 29 percent fewer deep vein thromboses (blood clots in a major vein) and pulmonary embolisms (blood clots in the lung) than women in the tamoxifen group. Specifically, 87 of 9,726 women in the tamoxifen group had a deep vein thrombosis compared to 65 of 9,745 women taking raloxifene. In addition, 54 of 9,726 women taking tamoxifen developed pulmonary embolisms compared to 35 of 9,745 women taking raloxifene. The number of strokes occurring in both groups of women was statistically equivalent: 53 of 9,726 women in the tamoxifen group and 51 of 9,745 women in the raloxifene group had a stroke during the trial. There was no difference in deaths from strokes: 6 of 9,726 women in the tamoxifen group and 4 of 9,745 women in the raloxifene group died from this event. Women at increased risk of stroke (those with uncontrolled hypertension or uncontrolled diabetes, or a history of stroke, transient ischemic attack, or atrial fibrillation) were not eligible to participate in STAR. While tamoxifen has been shown to reduce, by half, the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), raloxifene did not have an effect on these diagnoses. (LCIS and DCIS are sometimes called noninvasive breast cancers.) Of the 9,726 women taking tamoxifen, 57 developed LCIS or DCIS, 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).

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, M.D., 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.

The maker of tamoxifen, AstraZeneca Pharmaceuticals, Wilmington, Del., and the maker of raloxifene, Eli Lilly and Company, Indianapolis, Ind., provided their drugs and matching placebos for the trial without charge to participants. Eli Lilly and Company also gave NSABP support to defray recruitment costs at the participating centers and to help local investigators conduct the study.

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