10 years or less of extended adjuvant endocrine therapy for postmenopausal breast cancer patients: A systematic review and network meta-analysis

Introduction: Adjuvant hormonal therapy, with or without prior chemotherapy, has been widely recognised as the preferred treatment strategy for resected breast cancer (BC) for a minimum duration of 5 years. If the effectiveness of therapy beyond a 5-year period has been established, there is still ongoing debate regarding the optimal duration for this prolonged period. A network meta-analysis (NMA) was conducted to ascertain the optimal duration of extended therapy for resected BC in postmenopausal women.

Material and methods: A comprehensive search was conducted on online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, to identify all randomised trials on extended duration of endocrine therapy. The search was limited to trials that had been published before 30th April 2023. The study focused on evaluating disease-free survival (DFS) as the primary outcome, with overall survival (OS) as the secondary endpoint. Under the Bayesian framework, NMA was performed using the GeMTC package. The relative rankings of the treatments were determined by utilising surface under the cumulative ranking curve (SUCRA) p scores. A network meta-regression analysis was employed to ascertain the impact of the baseline characteristics of the disease and the initial treatments administered.

Results: In the overall population, increasing the duration by 5 years did not result in a significantly better DFS compared to durations of 2-3 and 3-4 more years (hazard ratio [HR] = 0.97, 95% confidence interval [CI] [0.88-1.08] and HR = 0.87, 95% CI [0.72-1.06]). This effect was independent of adjuvant chemotherapy and nodal status. However, the effect of 5 more years of AI was significantly better in node-positive BC and in those who received some years of tamoxifen instead of aromatase inhibitors (AIs) as initial adjuvant therapy. OS was not affected by the administration of extended endocrine therapy.

Conclusions: We conclude that an extended course of AI lasting 2-3 years, following an initial 5-year treatment, may be considered an appropriate regimen for achieving DFS benefits. In node-positive BC cases, it has been observed that a duration of 10 years provides a greater advantage compared to shorter durations, especially when tamoxifen is administered initially. Therefore, it is suggested that a longer duration is a potential standard of care in these cases.