ASCO--Postmenopausal women with osteoporosis who took raloxifene(Drug information on raloxifene) (Evista) for 2½ years to prevent fractures also had a significant 70% reduction in breast cancer risk, according to results of the Multiple Outcomes of Raloxifene Evaluation (MORE), reported at ASCO.
Raloxifene thus becomes the second selective estrogen-receptor modulator (SERM) to demonstrate a protective effect against breast cancer. As Oncology News International reported in April (page 1), the NSABPs Breast Cancer Prevention Trial (BCPT) found that tamoxifen(Drug information on tamoxifen) (Nolvadex) decreased breast cancer by 45% in high-risk women.
Although women treated with tam-oxifen in the NSABP trial showed an increase in endometrial cancer, compared with placebo recipients, no such excess was apparent in the MORE participants who received raloxifene. However, in his discussion of the two trials at the ASCO plenary session, C. Kent Osborne, MD, of the University of Texas Health Science Center, San Antonio, cautioned that, "at this point in time, we are only beginning to learn about the risks and benefits of each treatment."
While characterizing the early results of both trials as "exciting," he stressed that there are too few cases of endometrial cancer in the raloxifene trial to accurately determine the incidence of this cancer. He pointed out that the endometrial cancers seen with tamoxifen were all low-grade early cancers, and the excess cases were limited to women age 50 and older.
The MORE investigators randomized 7,705 osteoporotic women under age 80 to placebo or raloxifene (60 or 120mg/d), said Steven Cummings, MD, lead author and professor of medicine and epidemiology, University of California, San Francisco. Women with osteoporosis tend to have a somewhat lower risk of breast cancer, Dr. Cummings noted.
Over a median follow-up of 33 months, 13 cases of invasive breast cancer occurred in the raloxifene group vs 22 in the placebo arm. Dr. Cummings characterized this 70% risk reduction as "highly statistically significant" (P < .001).
Four women treated with placebo and four given raloxifene developed endometrial cancer. Dr. Cummings noted that "raloxifene is known to increase the risk of venous thrombosis and pulmonary emboli to a similar degree as seen with tamoxifen and estrogen." He added that the trial will continue, in a randomized fashion, for 5 more years to determine the long-term effects of raloxifene.
Although the NSABP tamoxifen trial was unblinded early due to its positive results with respect to breast cancer prevention, participants who chose to switch to or continue on tamoxifen also will be followed for a total of 6 to 10 years, D. Lawrence Wickerham, MD, associate chairman of the NSABP, said in the first formal presentation of the BCPT results.
"This trial is only the first step in breast cancer prevention," Dr. Wickerham said. He noted that a second NSABP prevention trial, the Study of Tamoxifen and Raloxifene (STAR), "will compare the now proven results of tamoxifen with the promising results of raloxifene."
This double-blind, randomized trial, slated to begin in the fall of 1998, will randomize 22,000 postmenopausal women at high risk of breast cancer to 5 years of therapy with tamoxifen or raloxifene.
"The NSABP and NCI are working to develop tools to aid women and their physicians in weighing the choice to begin tamoxifen therapy or not," Dr. Wickerham noted.
Until such tools are available, Dr. Osborne recommended considering SERM therapy in patients who share the characteristics of women who participated in the two trials (ie, osteoporosis or high breast cancer risk) but advised against extrapolating the results to the general population.