NEW YORK (Reuters Health) – The third generation aromatase inhibitor anastrozole may help prevent breast cancer in high-risk postmenopausal women, based on results of the IBIS-II trial.
Over five years, daily oral treatment with anastrozole cut the risk of breast cancer by 53% and was well tolerated, according to the study presented December 12 at the San Antonio Breast Cancer Symposium, to coincide with publication in The Lancet.
“Two other antihormone therapies, tamoxifen and raloxifene, are used by some women to prevent breast cancer, but these drugs are not as effective and can have adverse side effects, which limit their use,” Dr. Jack Cuzick noted in a conference statement. “Hopefully, our findings will lead to an alternative prevention therapy with fewer side effects for postmenopausal women at high risk for developing breast cancer.”
Dr. Cuzick is chairman of the IBIS-II steering committee, head of the Cancer Research UK Centre for Cancer Prevention, and director of the Wolfson Institute of Preventive Medicine at Queen Mary University of London.
Between February 2003 and January 2012, study investigators enrolled 3,864 postmenopausal women at increased risk of breast cancer. They randomly assigned 1,920 women to anastrozole (1 mg daily) and 1,944 to matching placebo.
After a median follow-up of five years, 40 women in the anastrozole group (2%) had developed breast cancer compared to 85 women in the placebo group (4%), yielding a hazard ratio of 0.47 with anastrozole treatment (p<0.0001).
The predicted cumulative incidence of breast cancer after seven years was 2.8% in the anastrozole group versus 5.6% in the placebo group. Eighteen deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0.836), the researchers report.
As important, they write, is the observation that most vasomotor side effects associated with estrogen deprivation were not attributable to the treatment.
“Almost 50% of controls reported hot flashes or night sweats and that was increased to about 57% with anastrozole; a small increase but a real increase,” Dr. Cuzick reported at a conference press briefing.
At the briefing, IBIS-II co-chair Dr. John Forbes from University of Newcastle in New South Wales, Australia, said anastrozole is an “important” option and “another choice” for high-risk women, but there is not a lot of awareness among the millions of women potentially able to benefit from it.
The IBIS-II findings are similar to those reported with exemestane in the MAP.3 trial. “Because anastrozole and exemestane have greater efficacies than do tamoxifen and raloxifene, and have a different but generally decreased side-effect profile, anastrozole or exemestane emerge as the treatments of choice for risk reduction in most postmenopausal women at high risk of breast cancer,” the investigators note in their study.
Dr. Cuzick said the plan is to follow the IBIS-II participants for at least 10 years. “We want to determine if anastrozole has a continued impact on cancer incidence even after stopping treatment, if it reduces deaths from breast cancer, and to ensure that there are no long-term adverse side effects,” he said.
In a comment published with the study, Dr. David Cameron of the Edinburgh Cancer Centre, Western General Hospital in Edinburgh, UK, agrees that longer follow-up of the cohort is needed.
Although the IBIS-II trial data are “important,” he writes, they do not address three challenges, described by Kinsinger and Harris in The Lancet in 2002 after publication of the IBIS-I tamoxifen chemoprevention trial.
“For chemoprevention to find a prominent role in reducing the burden of breast cancer, research must develop along at least three paths,” Kinsinger and Harris wrote. “First, longer-term research must find that the reduction in incidence translates into a reduction in breast cancer mortality. Second, newer drugs that have a better safety profile need to be developed. Finally, better ways are needed to target the drugs to those women who will benefit most.”
This study was supported by funds from Cancer Research UK, the National Health and Medical Research Council of Australia, AstraZeneca, and Sanofi-Aventis. Dr. Cuzick is on the speaker’s bureau for AstraZeneca.