Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials

Fausto Petrelli, Andrea Coinu, Mary Cabiddu, Mara Ghilardi, Veronica Lonati, Sandro Barni

Five years of adjuvant hormonal therapy is the standard of care in early breast cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant endocrine therapy is implemented to prevent recurrence and death; in particular, its carryover effect may prevent very late events. This meta-analysis compares the efficacy of 5 years of hormonal therapy alone with that of additional years of hormonal therapy, in patients with early BC. Randomised trials comparing 5 years versus more than 5 years of hormonal therapy in BC were identified by electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the fixed- or random-effects models. The primary endpoints were overall survival (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as odds ratios (ORs) and 95 % confidence interval (CI). Eight trials, including 29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy beyond 5 years of tamoxifen significantly improved OS (OR, 0.89; 95 % CI 0.80-0.99; P = 0.03), BCSS (OR, 0.78; 95 % CI 0.69-0.9; P = 0.0003) and RFS (OR 0.72; 95 % CI 0.56-0.92; P = 0.01) compared with 5 years of hormonal therapy alone. Loco-regional and distant relapses were reduced by 36 and 13 %, respectively. Compared with 5 years of tamoxifen, additional adjuvant endocrine therapy reduced risk of death and relapse of ER+ BC by ~10 and 30 %, respectively. This strategy should be considered in patients free of disease after 5 years of hormonal therapy.