Optimal extension time after initial endocrine therapy for postmenopausal hormone receptor-positive early-stage breast cancer: a systematic review and meta-analysis.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Prospero registration number: CRD42022335497.