Anastrozole provides long-term preventive effect for postmenopausal women at high risk for breast cancer
SAN ANTONIO — Anastrozole reduced breast cancer risk by 49% compared with placebo for postmenopausal women at high risk for the disease, according to long-term results of the randomized controlled IBIS-II trial presented at San Antonio Breast Cancer Symposium.
The findings — simultaneously published in The Lancet — showed no new major adverse events with anastrozole median follow-up of nearly 11 years.
“These long-term results are very encouraging” researcher Jack Cuzick, PhD, director of Wolfson Institute of Preventive Medicine and head of Centre for Cancer Prevention at Queen Mary University of London, told Healio. “We have confirmed that the benefit of [anastrozole] lasts long term. In addition, although there are early musculoskeletal events associated with aromatase inhibitors, in the long term this does not appear to impact compliance or increase the risk for fractures.”
The international, double-blind IBIS-II trial included 3,864 postmenopausal women at increased risk for breast cancer. Researchers established risk by family history, atypia and breast density.
Researchers randomly assigned study participants to 1 mg daily anastrozole (n = 1,920) or placebo (n = 1,944) for 5 years.
Investigators continued to follow women after treatment completion to assess breast cancer incidence, development of other cancers, death and major adverse events, including fractures and cardiovascular events.
Incidence of all breast cancer served as the primary outcome.
Initial results — presented in 2013 at San Antonio Breast Cancer Symposium — showed anastrozole reduced the risk for breast cancer by 53% at 5 years.
This year, Cuzick presented updated data based on median follow-up of 131 months (interquartile range, 105-156).
Results showed 85 breast cancer cases among women assigned anastrozole and 165 cases among women assigned placebo. This translated to a 49% reduction in breast cancer risk in the anastrozole group (HR = 0.51; 95% CI, 0.39-0.66).
Although the reduction observed with longer follow-up is slightly less than the earlier result, it remains statistically significant and also is a larger effect than that observed for tamoxifen, Cuzick said.
Researchers observed a 54% (HR = 0.46; 95% CI, 0.33-0.65) reduction in risk for invasive ER-positive breast cancers and a 59% (HR = 0.41; 95% CI, 0.22-0.79) reduction in risk for ductal carcinoma in situ — particularly for ER-positive lesions (HR = 0.22; 95% CI, 0.78-0.65).
Researchers also observed a 43% reduced risk for invasive HER2-negative breast cancers (HR = 0.57; 95% CI, 0.41-0.78) and a similarly reduced risk for HER2-positive breast cancers (HR = 0.52; 95% CI, 0.23-1.17).
Sixty-nine deaths occurred in the anastrozole group compared with 70 in the placebo group (HR = 0.96; 95% CI, 0.69-1.34). Two women assigned anastrozole and three assigned placebo died of breast cancer.
A significantly lower percentage of women assigned anastrozole developed non-breast cancers (147 vs. 200; OR = 0.72; 95% CI, 0.57-0.91), due primarily to cases of non-melanoma skin cancer.
Researchers reported no statistically significant increase in fractures (380 vs. 373; OR = 1.04; 95% CI, 0.88-1.22) or myocardial infarction (8 v. 6) between the anastrozole and placebo groups.
“Concerns regarding serious side effects — such as cardiovascular disease or risk for other cancers — were not observed,” Cuzick told Healio. “The concern regarding serious side effects are allayed, and the fact that the benefit will last at least longer than 12 years makes anastrozole the drug of choice for postmenopausal high-risk women. Some women cannot tolerate aromatase inhibitors and so they will have to be treated with tamoxifen, but my view is that the first choice should be anastrozole.” – by Jennifer Southall
Cuzick J, et al. Abstract GS4-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosure s : AstraZeneca, Cancer Research UK, National Health and Medical Research Council of Australia, and Sanofi funded this study. Cuzick reports a consultant role with Myriad Genetics, as well as research funding to his institution from AstraZeneca. Please see the abstract for all other authors’ relevant financial disclosures.