既往关于激素辅助治疗的随机对照研究，入组了任意HER2状态的患者；可是，对于占所有乳腺癌患者7～15%的雌激素受体（ER）伴HER2阳性患者，芳香酶抑制剂与他莫昔芬的不同作用可能被忽略。此外，绝经过渡时期往往需要数年，期间女性激素微环境发生变化，可能影响辅助治疗对他莫昔芬和芳香酶抑制剂的敏感性。由于既往研究排除了围绝经女性，仅仅入组已绝经女性，那么不同内分泌治疗对于诊断时年龄为45～55岁的ER伴HER2阳性乳腺癌围绝经女性效果如何？
2017年12月21日，欧洲癌症组织、欧洲癌症研究治疗组织、欧洲乳腺癌学会《欧洲癌症杂志》在线发表荷兰癌症研究所、乌得勒支大学医学中心、阿姆斯特丹安东尼·范·列文虎克医院、荷兰综合癌症组织、特文特大学的人群队列研究报告，使用来自荷兰癌症登记数据库全国人群的治疗和结局数据，将诊断时年龄作为绝经状态替代指标，对ER伴HER2阳性乳腺癌患者进行分组，比较了使用芳香酶抑制剂与他莫昔芬的有效性。
该研究通过荷兰癌症登记数据库找出2005～2007年所有被诊断为任何肿瘤大小和淋巴结分期、未转移、ER伴HER2阳性乳腺癌并接受过内分泌治疗的女性共1155例。根据诊断时年龄，将患者分为：未绝经（≤45岁326例）、围绝经（45～55岁304例）和已绝经（>55岁525例）。根据时间相关变量（接受芳香酶抑制剂或他莫昔芬的时间是否超过整个内分泌治疗期一半）对主要治疗进行亚组分析。使用生存曲线估算法对无复发生存和总生存进行评定，使用多因素风险比例回归法对化疗、曲妥珠单抗、诊断时年龄、淋巴结状态、分级、病理学肿瘤大小分期、卵巢切除等影响因素的风险比进行校正。
结果，随访期间发生237例复发和182例死亡。
芳香酶抑制剂与他莫昔芬相比，围绝经（45～55岁）女性的5年无复发生存（90%比78%）和总生存（96%比87%）显著获益，复发和死亡风险分别减少53%和63%（校正风险比：0.47、0.37，95%置信区间：0.25～0.91、0.18～0.79，P=0.026、0.010），而未绝经（≤45岁）女性对于芳香酶抑制剂与他莫昔芬的获益相似。这些年龄组之间的治疗效果显著不同（交互P=0.03、0.02）。已绝经女性对于芳香酶抑制剂获益小而不显著。
因此，对于ER伴HER2阳性围绝经（45～55岁）乳腺癌患者，芳香酶抑制剂治疗（最好无任何他莫昔芬治疗）与最佳的无复发生存和总生存相关。
未绝经、围绝经、已绝经乳腺癌女性的无复发生存曲线
未绝经、围绝经、已绝经乳腺癌女性的总生存曲线
Eur J Cancer. 2017 Dec 21;90:92-101.
Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis: A population-based cohort study.
G.M.H.E. Dackus, K. Józwiak, G.S. Sonke, E. van der Wall, P.J. van Diest, M. Hauptmann, S. Siesling, S.C. Linn.
Netherlands Cancer Institute, Amsterdam, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands; Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands; University of Twente, Enschede, The Netherlands.
HIGHLIGHTS
We studied all ER+/HER2+ Dutch breast cancer patients diagnosed between 2005 and 2007.
Aromatase inhibitors (AIs) and tamoxifen (TAM) were compared in a time-dependent way.
AIs not TAM significantly improve recurrence-free survival (RFS) and overall survival (OS) in perimenopausal women (45-55 years at diagnosis).
5-year RFS benefit for AI compared with TAM (90% vs. 78%; adjusted HR 0.47; P = 0.026).
5-year OS benefit for AI compared with TAM (96% vs. 87%; adjusted HR 0.37; P = 0.010).
BACKGROUND: Prior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7-15% of all breast cancer patients. In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR).
PATIENTS AND METHODS: All women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (45<years≤55; n = 304) and postmenopausal (>55 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation.
RESULTS: During follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25-0.91; P = 0.03) and HR 0.37 (95% CI 0.18-0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed.
CONCLUSION: AI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients.
KEYWORDS: Breast cancer; ER; HER2; Endocrine treatment; Survival analysis; Time-dependent analysis
DOI: 10.1016/j.ejca.2017.11.010
联系客服
