Investigators for the International Breast Cancer Intervention Study-I reported that tamoxifen reduced the incidence of breast cancer by 29% in women at high risk of the disease after a median follow-up of 16 years.
Investigators for the International Breast Cancer Intervention Study-I (IBIS-I) reported last week that tamoxifen significantly reduces the incidence of breast cancers in women at high risk for the disease and that the benefit persists for many years following treatment.
In the trial, more than 7,000 pre- and postmenopausal women ages 35 to 70 with a family history of breast cancer were randomly assigned to receive 20 mg of tamoxifen, or placebo, daily for 5 years. After a median follow-up period of 16 years, 246 women in the tamoxifen group developed breast cancers compared with 343 in the placebo group, a 29% reduction. The findings, presented on December 11 at the 2014 San Antonio Breast Cancer Symposium in Texas, were published concurrently in The Lancet Oncology.
“This trial was designed to prevent the occurrence of breast cancer, and it's achieved that very clearly over a long period,” says Jack Cuzick, PhD, professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University in London, UK. “Taking tamoxifen for 5 years gives women very long-term protection.”
Women in the tamoxifen group had more non-melanoma skin cancers (116 vs. 84) than those in the control group (116 vs. 84), a difference that was statistically significant. In addition, they had more endometrial (29 vs. 20) and lung (32 vs. 24) cancers, although those differences were not statistically significant. However, women who took tamoxifen had significantly fewer gastrointestinal cancers than did women in the control group (42 vs. 63).
“The most important risk we saw was for endometrial cancer,” says Cuzick. “Whereas tamoxifen is anti-estrogenic in the breast, preventing breast cancer cells from dividing, it appears to function as a stimulus for cell growth in the endometrium.”
Researchers also found that taking hormone replacement therapy (HRT) appears to interfere with the action of tamoxifen. Women who did not take HRT had a 45% reduction in estrogen receptor (ER)–positive breast cancers compared with a 35% reduction overall.
Despite the preventive benefit of tamoxifen, Cuzick noted that postmenopausal women seem to do even better with aromatase inhibitors. Early results from the IBIS-II trial, which includes almost 4,000 postmenopausal women at high risk for breast cancer, show that anastrozole reduced the risk of developing breast cancer by 53% compared with placebo.
“Tamoxifen is most appropriate for premenopausal women, for whom this long protection is particularly relevant,” he says. “For postmenopausal women, we recommend aromatase inhibitors as the first choice partly because of better efficacy and partly because there's no endometrial cancer risk when you get rid of estrogen completely.”
Although tamoxifen appears to significantly lower the incidence of ER-positive breast cancers, it did not affect the development of ER-negative breast cancers.
“The fact that we saw no effect on the incidence of ER-negative cancers is suggestive that taking tamoxifen has held some cancers at bay that would previously have appeared as ER-low positive,” says Cuzick. “What we've seen with this longer follow-up is that these cancers are not showing up until later, and when they do show up they are more often ER-negative.”
Researchers will continue to follow women in the IBIS-I trial for another 10 years.
“The average age of women who entered this trial was 50 and over 95% of them are still alive,” says Cuzick. “It will be another 5 to 10 years before we have good evidence on mortality.”