In a phase III trial reported in The New England Journal of Medicine, Michael Gnant, MD, and colleagues found no difference in disease-free survival with 2 vs 5 years of treatment with the aromatase inhibitor anastrozole in postmenopausal women with early hormone receptor (HR)-positive breast cancer who had received 5 years of adjuvant endocrine therapy. 

Michael Gnant, MD

Study Details

The multicenter trial included 3,470 eligible women (intention-to-treat [ITT] population) who had received 5 years (± 12 months) of adjuvant endocrine therapy with tamoxifen, aromatase inhibitors, or both sequentially up until 12 months prior to random assignment. They were randomly assigned between February 2004 and June 2010 to receive 2 years (n = 1,732) or 5 years (n = 1,738) of anastrozole at 1 mg/d.

The primary endpoint was disease-free survival in the primary analysis set of patients, including all patients still participating in the trial with no recurrence at 2 years after random assignment (when treatment in the 2-year group had ended).

Disease-Free Survival

Median follow-up from random assignment was 118.0 months (interquartile range = 97.8–121.1 months). Recurrence within the first 2 years was observed in 62 patients in the 2-year group and 65 in the 5-year group.

The primary analysis set consisted of 3,208 patients, including 1,603 in the 2-year group vs 1,605 in the 5-year group. Among these patients, disease-free survival events had occurred in 335 patients in each group at 8 years after the end of treatment in the 2-year group (10 years after random assignment).

Disease-free survival rates were 73.6% in the 2-year group vs 73.9% in the 5-year group (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.85–1.15, P = 0.90). After adjustment for potential confounding factors, the hazard ratio was 1.00 (95% CI = 0.86–1.16).

In the primary analysis set, contralateral breast cancer occurred in 2.2% vs 2.1% of patients (HR = 1.15, 95% CI = 0.75–1.77). A second primary cancer occurred in 6.2% vs 6.7% (HR = 1.06, 95% CI = 0.81–1.38). Local recurrence occurred in 3.0% vs 2.4%, distant recurrence in 5.1% vs 4.9%, and death without recurrence in 4.4% vs 5.0%.

Among 1,665 vs 1,670 patients remaining in the study after 2 years, 8-year overall survival rates were 87.5% vs 87.3% (HR = 1.02, 95% CI = 0.83–1.25). The risk of clinical bone fracture between 2 and 5 years after random assignment was 4.7% vs 6.3% (HR = 1.35, 95% CI = 1.00–1.84).

Adverse Events

Adverse events were consistent with the known toxicity profile of anastrozole. In the ITT population, serious adverse events occurred in 26.5% of patients in the 2-year group and 40.2% of those in the 5-year group; they were considered related to anastrozole in 2.3% vs 4.0%. The most common serious adverse event was osteoarthritis (1.7% vs 4.3%).

The investigators concluded, “In postmenopausal women with HR-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture.”

Disclosure: The study was funded by the Austrian Breast and Colorectal Cancer Study Group and AstraZeneca. For full disclosures of the study authors, visit nejm.org.