The Efficacy And Safety Of Using The Aromatase Inhibitors And The Estrogen Receptor Modulator For Postmenopausal Women With Breast Cancer: A Meta-Analysis

Objective: To compare the efficacy and safety of using the third generation aromatase inhibitors sequential tamoxifen and aromatase inhibitors or tamoxifen alone in neo-adjuvant endocrine therapy for postmenopausal patients with hormonedependent.Methods: We retrieved relevant literature in Cochrane,PubMed,Embase,China hownet database,and WanFang database,according to established standards for the third generation aromatase inhibitors sequential tamoxifen and aromatase inhibitors or tamoxifen alone in neo-adjuvant endocrine therapy for postmenopausal patients with hormone-dependent randomized controlled trials,with the quality evaluation by Cochrane system.The extracted data was systematically analyzed with RevMan5.3.and the results of contrast were evaluated by using hazard ratio(HR)and odds ratio(OR).Results: According to established standards,a total of 10 articles were included in and 22,005 postmenopausal patients with hormone-dependent were selected for meta-analysis.7 studies including 7,592 patients were about the sequential therapy compared to tamoxifen monotherapy and 3 studies including 14,413 patients about the sequential therapy compared to aromatase inhibitors monotherapy.Statistical analysis showed that the sequential therapy,in comparison with tamoxifen monotherapy achieve longer survival: overall survival HR=0.71(95%CI 0.52-0.98,P=0.04),recurrence-free survival HR=0.60(95%CI 0.46-0.79,P=0.0003),and reduces the incidence of death OR=0.70(95%CI 0.59-0.83,P<0.0001),the incidence of distant metastasis OR=0.76(95%CI 0.62-0.92,P=0.006).However,no significant difference was observed in survival benefit between the sequential therapy and aromatase inhibitors monotherapy,overall survival HR=1.01(95%CI 0.93-1.11,P=0.79),disease free survival HR=1.01(95%CI 0.93-1.09,P=0.89).About adverse events,compared with tamoxifen monotherapy,the sequential therapy reduces the incidence of endometrial hyperplasia OR=0.23(95%CI 0.11-0.46,P<0.0001),the incidence of endometrial cancer OR=0.18(95%CI 0.04-0.82,P=0.03);And has not obviously ascending the incidence of local recurrence OR=0.81(95%CI 0.62-1.05,P=0.11),the incidence of genital bleeding OR=0.87(95%CI 0.63-1.20,P=0.40),the incidence of heart disease OR=0.91(95%CI 0.54-1.51,P=0.70),the incidence of thrombus/embolism OR=0.61(95%CI 0.27-1.38,P=0.24),the incidence of fever OR=0.94(95%CI 0.77-1.15,P=0.55);However,the incidence of bone fracture events is higher in those undergo sequential therapy compared with those accept tamoxifen monotherapy: OR=1.30(95%CI 1.13-1.51,P=0.0004).Compared with aromatase inhibitors monotherapy,the sequential therapy reduces the incidence of bone fracture,heart disease;And has not obviously ascending the incidence of endometrial cancer,death,and local recurrence;And adds the incidence of endometrial hyperplasia,genital bleeding,thrombus/embolism,distant metastasis,fever.Conclusion: The sequential therapy has better effect and security compared to tamoxifen monotherapy.However,there is no significant difference in survival benefit for patients between the sequential therapy and aromatase inhibitors monotherapy.