|Initial Results of the Study of Tamoxifen and Raloxifene (STAR)
Released: Osteoporosis Drug Raloxifene Shown to be as Effective as Tamoxifen
in Preventing Invasive Breast Cancer
Initial results of the Study of Tamoxifen and Raloxifene, or STAR, show that
the drug raloxifene, currently used to prevent and treat osteoporosis in postmenopausal
women, works as well as tamoxifen in reducing breast cancer risk for postmenopausal
women at increased risk of the disease. In STAR, both drugs reduced the risk
of developing invasive breast cancer by about 50 percent. In addition, within
the study, women who were prospectively and randomly assigned to take raloxifene
daily, and who were followed for an average of about four years, had 36 percent
fewer uterine cancers and 29 percent fewer blood clots than the women who were
assigned to take tamoxifen. Uterine cancers, especially endometrial cancers,
are a rare but serious side effect of tamoxifen. Both tamoxifen and raloxifene
are known to increase a woman’s risk of blood clots.
STAR, one of the largest breast cancer prevention clinical trials ever conducted,
enrolled 19,747 postmenopausal women who were at increased risk of the disease.
Participants were randomly assigned to receive either 60 mg of raloxifene (Evista®)
or 20 mg of tamoxifen (Nolvadex®) daily for five years. The trial
is coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP),
a network of cancer research professionals, and is 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, M.D., 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, M.D., 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."
Women taking either drug had equivalent numbers of strokes, heart attacks, and
bone fractures. Both raloxifene and tamoxifen are known to protect bone health;
it is estimated that half a million postmenopausal women are currently taking
raloxifene by prescription 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.
“Although no drugs are without side effects, tamoxifen and raloxifene are vital
options for women who are at increased risk of breast cancer and want to take
action,” said Leslie Ford, M.D., associate director for clinical research in
NCI’s Division of Cancer Prevention. “For many women, raloxifene’s benefits will
outweigh its risks in a way that tamoxifen’s benefits do not.”
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.
Study details include:
- 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
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.
For more information about STAR, including links to media materials and a fact
sheet, visit NCI's STAR home page at http://www.cancer.gov/star or
NSABP’s Web site at http://www.nsabp.pitt.edu or http://foundation.nsabp.org.
For a Q&A related to the STAR results, go to: http://www.cancer.gov/newscenter/pressreleases/STARresultsQandA.
For B-roll related to the STAR results, go to www.thenewsmarket.com for
digitized, downloadable B-roll, or call the NCI Media Relations Branch at (301)
496-6641 for a Beta-tape copy.
For tools used to calculate a woman’s risk of breast cancer, visit http://cancer.gov/bcrisktool or http://breastcancerprevention.com.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.