Optimal extension time after initial endocrine therapy for postmenopausal hormone receptor-positive early-stage...

The optimal duration of extended endocrine therapy (ET) for women with hormone receptor-positive (HR-positive) early-stage postmenopausal breast cancer remains uncertain. This meta-analysis systematically evaluated the optimal time to prolong aromatase inhibitors ( AIs) therapy for postmenopausal early stage breast cancer who received initial endocrine therapy.

PubMed, Web of Science, Ovid, Scopus, EmBase, and Cochrane Library were searched for randomized controlled trials (RCTs) using keywords related to breast cancer, HR-positive, AIs, and tamoxifen (TAM). Disease-free survival (DFS) was used as the primary endpoint. Meta-analysis was performed using STATA 16.0 and Revman 5.4 statistical software. Hazard ratio (HR) with its corresponding 95% confidence intervals (CI) was used as an effective indicator to assess DFS, OS, and subgroups of extended ET. Relative ratio (RR) was used to assess adverse events.

The study included four RCTs involving 8,748 patients with HR-positive breast cancer. Pooled data showed an improvement in DFS when extending endocrine therapy from 5 to 7-8 years (HR = 0.82, 95% CI: 0.73 ~ 0.93), especially in patients with tumor size ≥ 2 cm (HR = 0.69, 95% CI: 0.49 ~ 0.98), estrogen receptor (ER) and progesterone receptor (PR) positive (HR = 0.77, 95% CI: 0.67 ~ 0.89), human epidermal growth factor receptor 2 (HER-2) positive or negative (HR = 0.85, 95% CI: 0.74 ~ 0.97; HR = 0.44, 95% CI: 0.22 ~ 0.89) and previous chemotherapy (HR = 0.80, 95% CI: 0.68 ~ 0.95). However, DFS has not improved with the extension from 7-8 to 10 years (HR = 0.97, 95% CI: 0.85 ~ 1.10). Furthermore, we found no significant difference in overall survival (OS), adverse events (AEs) analysis revealed a significant increase in the incidence of arthralgia, osteoporosis, bone fractures and asthenia after extended AIs.

The proportion of patients with breast cancer receiving ET extended beyond 5 years has increased, while the extension of AIs treatment from 5 to 7-8 years may be an option for high-risk patients with well-tolerated tumor size ≥ 2 cm, HR-positive, and previous chemotherapy. However, a variety of adverse events may accompany ET therapy, the identification of factors that may benefit breast cancer patients requires further randomized controlled studies.

CRD42022335497.