A 10-year median follow-up analysis of the IBIS-II trial on the efficacy and safety of the aromatase inhibitor anastrozole for healthy postmenopausal women at increased risk of developing breast cancer has found that the therapy reduced the likelihood of breast cancer incidence by 50% and had few side effects. The results from this updated study analysis indicate a long-term preventive benefit with anastrozole from estrogen receptor (ER)-positive breast cancer in postmenopausal women. The study by Cuzick et al was presented at the 2019 San Antonio Breast Cancer Symposium (Abstract GS4-04) and was simultaneously published in The Lancet.
Study Methodology
From 2003 to 2012, the researchers enrolled 3,864 postmenopausal women at increased risk of developing breast cancer into the IBIS-II Prevention study, a double-blind trial of anastrozole (n = 1,920) vs matching placebo (n = 1,944) for 5 years. The primary objective of this study was to determine the efficacy of anastrozole in preventing breast cancer overall (both invasive disease and ductal carcinoma in situ [DCIS]) and particularly for the post–5-year time period. Secondary endpoints included prevention of ER-positive breast cancer, breast cancer mortality, non–breast cancer–related deaths, other cancers, cardiovascular disease, fractures, and musculoskeletal events.
Results
KEY POINTS
- In the IBIS-II study, breast cancer incidence among postmenopausal women at high risk for developing the disease continued to be significantly reduced 5.9 years after stopping 5 years of anastrozole.
- After a median follow-up of 10.9 years, women assigned to anastrozole were 50% less likely to develop breast cancer than women assigned to the placebo arm of the study.
- No new adverse side effects from anastrozole were detected from those reported in an earlier analysis in 2013, which included small increases in muscle aches and pains and hot flashes.
After a median follow-up of 10.9 years, the researchers reported a total of 241 breast cancers (hazard ratio [HR] = 0.50, P < .0001) in the study population. The reduction was larger in the first 5 years of use (HR = 0.39, P < .0001) but was still significant after 5 years (117 [49%] new cases; HR = 0.63, P = .015). The effects in the two time periods were not significantly different (P = .11).
Invasive ER-positive breast cancer was reduced by 54% with anastrozole treatment (HR = 0.46, P < .0001), with a continued significant effect observed in the posttreatment follow-up period. A nonsignificant effect was observed in invasive ER-negative breast cancer (HR = 0.76, P = .4). A reduction in DCIS overall was observed, with a very large reduction in those cases known to be ER-positive (HR = 0.23, P < .0001).
A total of 129 deaths have been reported, with no significant difference in all-cause mortality between the two treatment arms (63 vs 66; HR = 0.93, P = .7). Only five deaths from breast cancer (two vs three) were reported, but the number of events are is small and longer follow-up is needed.
Approximately 320 cancers other than those of the breast were reported, with a significant decrease observed with anastrozole treatment (129 vs 192; odds ratio = 0.66, P = .0004). Specifically, fewer endometrial cancers (4 vs 8), ovarian cancers (5 vs 9), lung cancers (5 vs 12), and melanomas (9 vs 18) were observed in patients who were treated with anastrozole.
“This updated analysis of the IBIS-II trial confirms the significant reduction in breast cancer occurrence with anastrozole in the posttreatment follow-up period. These results indicate a long-term preventive benefit with anastrozole for ER-positive breast cancer in postmenopausal women,” concluded the study authors.
Clinical Significance
Jack Cuzick, PhD
“The 50% reduction in likelihood of breast cancer incidence after 10.9 years of follow-up is slightly less than the 53% reduction we reported after the first 7 years of follow-up, but it is still a significant effect and larger than that seen for tamoxifen,” said lead study author Jack Cuzick, PhD, Director of the Wolfson Institute of Preventive Medicine, Head of the Center for Cancer Prevention, and John Snow Professor of Epidemiology at Queen Mary University of London, in a statement.
“Another way to consider the data," he continued, "is that it translates into an estimated 29 women needing to be treated with anastrozole for 5 years to prevent one breast cancer during treatment and in the next 5 years. This is far fewer women than the estimated 49 women that need to be treated with tamoxifen for 5 years to prevent one breast cancer in the same time period. Therefore, our new results strongly suggest that anastrozole should be preferred therapy for breast cancer prevention in postmenopausal women at increased risk for the disease, with tamoxifen used for women who experience severe side effects from anastrozole.”
Disclosure: Funding for this study was provided by AstraZeneca, Cancer Research UK, and the National Health and Medical Research Council Australia. For full disclosures of the study authors, visit abstractsonline.com or thelancet.com.
