卵巢功能抑制治疗雌激素受体阳性早期乳腺癌的短期效应和长期生存的影响因素分析

Factors-associated with short-term effect and long-term survival of ovarian function suppression in estrogen receptor positive breast cancer: a retrospective analysis

背景与目的:内分泌治疗已经是激素受体阳性乳腺癌患者手术后辅助治疗的常规手段之一。本研究旨在分析影响可手术乳腺癌患者接受卵巢功能抑制(ovarian function suppression,OFS)治疗后短期效应(雌激素抑制效果)和长期生存(无病生存期)的影响因素。方法:回顾性分析2017年6月—2019年6月于复旦大学附属肿瘤医院行手术且完成术后标准化疗和内分泌治疗(OFS联合他莫昔芬或芳香化酶抑制剂)的435例雌激素受体(estrogen receptor,ER)阳性乳腺癌患者的临床病理学资料和无病生存期(disease-free survival,DFS)。采用单因素和多因素logistic回归分析对雌激素抑制效应有影响的因素,并运用log-rank检验和Cox比例风险回归模型分析对患者DFS有影响的因素。结果:OFS治疗后,年龄≤35岁患者雌激素抑制失败率为8.7%,显著高于35~40岁患者1%的雌激素抑制失败率(P<0.05);不同OFS药物如戈舍瑞林和亮丙瑞林的雌激素抑制作用基本一致(P>0.05)。内分泌治疗方案(HR=0.49,P<0.05)、腋窝淋巴结状态(HR=4.21,P<0.05)和肿瘤直径(HR=2.00,P<0.05)均是患者DFS的独立预后因素;虽然雌激素抑制失败患者倾向预后较差(P=0.10),但不同OFS药物对降低复发转移的疗效也一致。结论:年龄是乳腺癌患者采用OFS治疗后短期雌激素抑制失败的独立危险因素;内分泌药物、腋窝淋巴结状态以及肿瘤直径会影响ER阳性可手术乳腺癌患者的长期预后;无论是戈舍瑞林还是亮丙瑞林对患者降低雌激素水平和长期无病生存期差异无统计学意义。

Background and purpose: Endocrine therapy has been one of the routine means of adjuvant therapy for patients with hormone receptor positive after surgery. This study aimed to analyze the factors influencing short-term effect(estrogen suppression effect) and long-term survival(disease-free survival, DFS) in patients with operable breast cancer after ovarian function suppression(OFS) therapy. Methods: DFS data and clinicopathological parameters for 435 patients with estrogen receptor(ER) positive breast cancer who underwent surgery and completed postoperative standard chemotherapy and endocrine therapy(OFS combined with tamoxifen or aromatase inhibitors) between June 2017 to June 2019 were obtained in Fudan University Shanghai Cancer Center. The authors performed univariate logistic regression and multivariate logistic regression to analyze the influencing factors of estrogen suppression, while log-rank test and COX proportional hazards regression model were used to analyze the influencing factors of disease-free survival. Results: The failure rate of estrogen suppression in patients aged ≤35 years was 8.7%, which was significantly higher than that in patients aged 35-40 years(1%, P<0.05). There was no difference in the level of estrogen decline between goserelin and leuprorelin(P>0.05). Endocrine therapy regimen(HR = 0.49, P<0.05), axillary lymph node status(HR = 4.21, P<0.05), and tumor diameter(HR = 2.00, P<0.05) were all influencing factors of patients’ DFS;The prognosis of patients with estrogen suppression failure was poor(P = 0.10), but the efficacy of goserelin and leuprorelin in reducing recurrence and metastasis was consistent. Conclusion: Age is an independent risk factor for the failure of short-term estrogen suppression in breast cancer patients treated with OFS. Endocrine therapy regimen, axillary lymph node status and tumor diameter affect the long-term prognosis of patients with ER-positive operable breast cancer. There was no significant difference in the reduction of estrogen levels and longterm disease-free survival between patients with goserelin and leuprorelin.