WASHINGTON -- Women at high risk for breast cancer benefited from
treatment with tamoxifen or raloxifene (Evista), according to long-term data
from a large, randomized clinical trial.
After a median follow-up of almost seven years, tamoxifen edged ahead of
raloxifene for prevention of invasive breast cancers, which were 24% more common
in the raloxifene group, investigators reported here at the American Association
for Cancer Research meeting.
The two agents demonstrated similar effectiveness for preventing noninvasive
breast cancer.
Raloxifene had a significant advantage in toxicity and tolerability, including
substantial reductions in the risk of endometrial cancer, uterine hyperplasia,
and thromboembolic events.
The difference translated into a higher rate of nonadherence in the tamoxifen
group, D. Lawrence Wickerham, MD, National Surgical Adjuvant Breast and Bowel
Project in Pittsburgh, said at an AACR press briefing.
"These data are good news for postmenopausal women who want to reduce their risk
of breast cancer," he declared. "I see women each week in a high-risk clinic,
and I end up telling one or two of them, all too often, that they have a breast
cancer. I'd love for that part of my job to go away. These data are a step in
that direction."
The Study of Tamoxifen and Raloxifene (STAR) involved 19,747 healthy, high-risk
postmenopausal women randomized to tamoxifen or raloxifene for five years.
After 47 months of follow-up, both groups had about a 50% reduction in breast
cancer incidence compared with historical data on untreated women (JAMA 2006;
295: 2727-41).
At
that point, raloxifene and tamoxifen appeared equally effective against invasive
cancer, but raloxifene was somewhat less effective for preventing noninvasive
cancer. Analyses of toxicity and adverse effects favored raloxifene.
The updated analysis, after a median follow-up of 81 months, showed that
patients in the raloxifene group had a 1.24 relative risk of invasive breast
cancer compared with the tamoxifen group (95% CI 1.05 to 1.47), an increase from
the 47-month analysis.
Raloxifene-treated patients had a relative risk of 1.22 for noninvasive breast
cancer versus tamoxifen, a narrowing of the difference from the earlier analysis
(95% CI 0.95 to 1.59).
In an article published simultaneously in Cancer Prevention Research, Wickerham
and colleagues put the results into context.
They noted that tamoxifen reduced the risk of breast cancer by 50% compared with
untreated women in the Breast Cancer Prevention Trial (J Natl Cancer Inst 1998;
90: 1371-88).
The 1.24 relative risk of invasive cancer with raloxifene versus tamoxifen meant
that raloxifene was 76% as effective as tamoxifen, which translated into a 38%
reduction in the risk of invasive breast cancer, compared with untreated women.
Comparing toxicity between treatment groups yielded several significant
differences in favor of raloxifene:
* Invasive uterine cancer, RR 0.55 (95% CI 0.36 to 0.83)
* Uterine hyperplasia, RR 0.19 (95% CI 0.12 to 0.29)
* Thromboembolic events, RR 0.75 (95% CI 0.60 to 0.93)
* Hysterectomy, RR 0.45 (95% CI 0.37 to 0.54)
* Cataracts, RR 0.80 (95% CI 0.72 to 0.89)
Mortality did not differ significantly between treatment groups (236 deaths in
the tamoxifen arm, 202 with raloxifene) but trended in favor of raloxifene (RR
0.84, 95% CI 0.70 to 1.02).
More patients dropped out of the tamoxifen group than the raloxifene group
(38.9% versus 27.4%).
At the AACR press briefing, Gabriel Hortobagyi, MD, of the M.D. Anderson Cancer
Center in Houston, said the updated STAR results reinforce an existing large
body of evidence showing that selective estrogen receptor modulators, such as
tamoxifen and raloxifene, prevent breast cancer in high-risk women.
With the efficacy proven, the emphasis should shift toward increasing the use of
the agents.
"We need to reassess why we are not using these drugs more broadly and why we
are not prepared to reduce the risk of breast cancer by about 50% in high-risk
women," said Hortobagyi.
Source : MedPage Today
