Background
Phase III, double-blind, placebo-controlled RCT. 3864 postmenopausal women at elevated breast cancer risk (family history, prior LCIS/atypical hyperplasia, or other risk factors). Tested anastrozole — an aromatase inhibitor — as a breast cancer chemoprevention agent in postmenopausal women. Anastrozole reduces estrogen synthesis and was hypothesized to reduce ER-driven BC development.
Interventions and follow up
Arm A: Anastrozole 1mg daily for 5 years
Arm B: Placebo for 5 years
Primary endpoint: All breast cancer (invasive + non-invasive) incidence
mFollow up: 131 months (10-yr analysis)
Arm B: Placebo for 5 years
Primary endpoint: All breast cancer (invasive + non-invasive) incidence
mFollow up: 131 months (10-yr analysis)
Results
BC incidence (10-yr): 8.7% vs 14.2% (anastrozole vs placebo), HR 0.53, 95% CI 0.44–0.64, P<.0001
Invasive ER+ BC: HR 0.54, P<.0001
OS: Similar between arms — no mortality reduction
Invasive ER+ BC: HR 0.54, P<.0001
OS: Similar between arms — no mortality reduction
Adverse events
Vasomotor/genitourinary: Hot flashes more common with anastrozole (57% vs 47%); vaginal dryness and sexual dysfunction higher.
Musculoskeletal: Musculoskeletal complaints higher with anastrozole; fractures 6% vs 5% (not statistically significant).
Other: No increase in cardiovascular events or non-breast malignancies.
Musculoskeletal: Musculoskeletal complaints higher with anastrozole; fractures 6% vs 5% (not statistically significant).
Other: No increase in cardiovascular events or non-breast malignancies.
Conclusions
Anastrozole reduced breast cancer incidence by 47% over 10 years in high-risk postmenopausal women, with the benefit concentrated in ER-positive BC. IBIS-II established anastrozole as a guideline-endorsed chemoprevention agent in postmenopausal high-risk women.
Key Limitations
No OS or breast cancer mortality benefit demonstrated — chemoprevention reduces incidence but not established mortality. Adherence to 5-year preventive therapy is a major real-world challenge (~25–30% discontinuation). Benefit is restricted to ER+ BC; anastrozole does not prevent ER– or HER2+ BC. Prolonged AI exposure raises concerns about bone loss in the prevention context — DXA monitoring recommended. Not applicable to premenopausal women.
Clinical Context
IBIS-II, alongside MAP.3 (exemestane), established AIs as preferred chemoprevention options for postmenopausal high-risk women. ASCO guidelines recommend anastrozole or exemestane as chemoprevention for postmenopausal women (over tamoxifen) given favorable tolerability (no uterine cancer or thromboembolic risk). Bone density monitoring is recommended. Uptake in clinical practice remains low — decision aids and counseling are critical. ESMO-MCBS: not applicable (prevention trial).