芳香化酶抑制剂联合卵巢功能抑制对绝经前乳腺癌患者血脂水平的影响

Effects of aromatase inhibitors combined with ovarian function suppression on lipid levels in premenopausal breast cancer patients

目的 探讨不同芳香化酶抑制剂联合卵巢功能抑制(ovarian function suppression,OFS)对绝经前术后辅助内分泌治疗的乳腺癌患者血脂代谢的影响。方法 纳入2019年1月至2022年12月于大同市第三人民医院收治的符合研究标准的161例绝经前乳腺癌患者的临床资料。将所有患者分为来曲唑+OFS组55例、阿那曲唑+OFS组47例和依西美坦+OFS组59例三组,分析治疗前,治疗后6个月、12个月、24个月、36个月5个时间点总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)的差异,并进行年龄分层研究。结果 与治疗前相比,三组患者的TC水平在治疗后12个月、24个月和36个月的升高差异均有统计学意义;TG水平在来曲唑+OFS组和阿那曲唑+OFS组的12个月、24个月和36个月的升高差异均有统计学意义;LDL-C水平在来曲唑+OFS组和阿那曲唑+OFS组治疗后24个月和36个月均显著升高,在依西美坦+OFS组治疗后12个月和36个月也显著性升高;HDL-C水平分别在阿那曲唑+OFS组治疗后12个月、24个月和依西美坦+OFS组治疗后6个月、24个月显著下降。组间比较,来曲唑+OSF组和阿那曲唑+OFS组对TC水平的升高作用显著强于依西美坦+OFS组(P=0.044、P=0.038);TG和LDL-C组间比较差异无统计学意义;依西美坦+OFS组降低HDL-C的作用显著强于其他两组(P=0.001、P<0.001)。亚组分析,来曲唑+OFS组≥50岁亚组治疗后6个月、12个月和24个月TC水平升高更显著(P=0.03,P=0.024,P=0.02);阿那曲唑+OFS组≥50岁亚组治疗后24个月和36个月LDL-C水平升高更显著(P=0.041,P=0.017);治疗后24个月和36个月时间点阿那曲唑+OFS组≥50岁亚组HDL-C水平降低更显著(P=0.031,P=0.022)。结论 芳香化酶抑制剂联合OFS可引起绝经前乳腺癌患者TC、TG、LDL-C水平的升高和HDL-C水平的降低,且以非甾体类芳香化酶抑制剂对血脂的影响更大,通过加强对该类患者血脂水平的检测,对预防潜在的血脂异常及心血管不良事件发生的风险具有重要的临床价值。

Objective This retrospective study aimed to evaluate the effects of adjuvant endocrine therapies on lipid profiles in premenopausal patients with hormone receptor(HR)positive breast cancer.Methods A total of 161 patients were involved from January 2019 to December 2022 in The Third People's Hospital of Datong.they were devided into three groups:letrozole plus ovarian function suppression group(letrozole+OFS group),anastrozole plus OFS group(anastrozole+OFS group)and exemestane plus OFS group(exemestane+OFS group).Serum lipid parameters including total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were recorded at baseline,6,12,24 and 36 months(m)after the initiation of endocrine therapy.Results Compared to the baseline,TC level in all groups significantly increased at 12m、24m and 36m;Significant difference of TG level was found between letrozole+OFS group and anastrozole+OFS group at 12m、24m and 36m;LDL-C level was also significantly higher between letrozole+OFS group and anastrozole+OSF group at 24m and 36m,The same significant difference was also detected in exemestane+OFS group at 12m and 36m;Patients in anastrozole+OFS group at 12m and 24m and exemestane+OFS group at 6m and 12m also had significantly lower HDL-C level(P=0.001,P<0.001).The comparison in groups:For exemestane+OFS group,Letrozole+OFS group and anastrozole+OFS group significantly increased TC level(P=0.044,P=0.038),while exemestane+OFS group significantly decreased HDL-C levels.Subgroup analysis:in≥50 years Subgroup,significant difference of TC level was detected in letrozole+OFS group at 6m,12m and 24m(P=0.03,P=0.024,P=0.02),LDL-C and HDL-C level was detected in anastrozole+OFS group at 24m and 36m(P=0.041,P=0.017,P=0.031,P=0.022).Conclusions Application of endocrine therapy with AI plus OFS may increase the levels of TC,TG and LDL-C,while decrease HDL-C level in premenopausal breast cancer patients,especially non-steroidal AI has a greater effect on lipid metabolism than steroidal AI.More attention should be taken for endocrine therapy with AI plus OFS induced lipid disorder during the treatment.