Postoperative Adjuvant Anastrozole for 10 Rather than 5 Years in Patients with Oestrogen Receptor-Positive Breast Cancer: AERAS, a Randomised Multicentre Open-Label Phase III Trial

Background: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on the risk of breast cancer recurrence. Methods: This prospective, randomised, multicentre open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after treatment with either 5 years of anastrozole alone or 2–3 years of tamoxifen followed by 2–3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole (1 mg/day orally) for an additional 5 years or stop anastrozole, using the central computer at the Comprehensive Support Project for Oncology Research Data Centre. Randomisation was stratified by type of postoperative endocrine therapy, nodal status, prior adjuvant chemotherapy, and facility. The primary endpoint was disease-free survival, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with UMIN clinical trials registry, number UMIN000000818. Findings: We enrolled 1697 patients from 117 facilities between November 2007 and November 2012. Patients were assigned randomly to the continue group (n=849) or the stop group (n=848). Follow-up information was available for 1593 patients (n=787 in the continue group, n=806 in the stop group) as the full analysis set. After a median follow-up of 5·1 years, there were 172 events involving disease recurrence or the occurrence of contralateral breast cancer (75 in the continue group and 97 in the stop group) and 40 deaths (21 in the continue group and 19 in the stop group). The 5-year disease-free survival rates were 91% (95% confidence interval [CI] 89–93) in the continue group and 86% (95% CI 83–88) in the stop group (hazard ratio [HR] for disease-free survival 0·61, 95% CI 0·46–0·82; p<0·0010, two-sided log-rank test). The 5-year overall survival rates were 98% in the continue group and 98% in the stop group (HR 1·13, p=0·7042). The 5-year distant disease-free survival rates were 95% in the continue group and 93% in the stop group (HR 0·68, p=0·0553). Sixty-seven second primary cancers occurred, including 24 in the continue group and 43 in the stop group. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than in the stop group, including higher incidences of hot flashes (111 [14%] vs 81 [10%]), stiff joints (162 [21%] vs 98 [12%]), arthralgia (294 [37%] vs 236 [29%]), and new-onset osteoporosis (370 [47%] vs 355 [44%]). Interpretation: Continuing adjuvant anastrozole for an additional 5 years after 5 years’ initial treatment with anastrozole or tamoxifen is safe and beneficial in postmenopausal patients with hormone receptor-positive breast cancer. Trial Registration: This study is registered with UMIN clinical trials registry, number UMIN000000818. Funding: The Comprehensive Support Project for Oncology Research of the Public Health Research Foundation Declaration of Interest: None to declare. Ethical Approval: Ethical approval was provided by local ethics committees in each hospital.