Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least ten years after completion of therapy.

This randomised open label phase 3 trial, recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor positive early breast cancer, who had completed ≥4 years of endocrine therapy (aromatase inhibitor, tamoxifen, ovarian suppression, or sequential combination) ≥1 year prior, to oral letrozole 2.5mg daily for five years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. Secondary outcomes were disease free survival, overall survival and safety.

Between 16(th) May 2007 and 14(th) March 2012, 181 patients were randomised to letrozole, and 179 to observation (median age 64.3 years). Endocrine therapy was completed a median of 2.6 years prior to randomisation, and 47.5% had tumours >2cm and/or node positive. At 3.9 years median follow-up (IQR 3.8-4.0), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% CI 3.8%-13.0%, log rank test p=0.0004). Twenty-four patients (13.4%) in the observation and fourteen (7.7%) in the letrozole arm experienced a disease free survival event (log rank p=0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole.

These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor positive breast cancer, and offer insight into reintroduction of aromatase inhibitor therapy.