Optimal duration of endocrine therapy with extended aromatase inhibitors for postmenopausal patients with hormone receptor-positive breast cancer: a meta-analysis.

Abstract

The optimal duration of endocrine therapy for patients with hormonereceptor-positive (HR-positive) breast cancer is still unclear. This meta-analysis aims to determine the optimal duration of endocrine therapy with extended aromatase inhibitors(AI) for postmenopausal patients with HR-positive early breast cancer who have finished 5years of endocrine therapy. Eligible randomized controlled trials were classified into three categories according to the whole duration of endocrine therapy (10years versus 5years, 7-8years versus 5years, and 10years versus 7-8years). For each category, hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS), and risk ratio (RR) for the incidence of adverse events were pooled. Altogether 9 RCTs enrolling a total of 22,313 postmenopausal women with HR-positive breast cancer were included. Pooled data showed an improvement in DFS when extending endocrine therapy from 5 to 7-8years (HR = 0.79 [0.69, 0.91]), specifically among those who had been treated with only tamoxifen (HR = 0.40 [0.22, 0.73]) or sequential tamoxifen followed by AI (HR = 0.82 [0.71, 0.95]), with tumors that were node-positive (HR = 0.72 [0.56, 0.93]), estrogen receptor (ER) and progesterone receptor (PR) positive (HR = 0.61 [0.47, 0.78]), or ≥ 2cm in size (HR = 0.72 [0.51, 0.98]). However, no improvement in DFS was obtained when extending from 7-8 to 10years (HR = 0.98 [0.87, 1.11]). In addition, the extension of endocrine therapy was not associated with an improvement in OS, but was associated with an increased risk of bone fracture and osteopenia/osteoporosis. Patients who have been treated with AI for 5years, with tumors that are node-negative, ER+/PR- or ER-/PR+, and < 2cm in size do not need to receive extended AI therapy. For those who have been treated with only tamoxifen or sequential tamoxifen followed by an AI for a total of 5years, with tumors that are node-positive, ER+/PR+ or ≥ 2cm in size, 2-3years of extended AI is necessary and maybe enough.