Division of Medical Oncology, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Canada; King Fahad Medical City, Riyadh, Saudi Arabia.
Division of Medical Oncology, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Canada; Davidoff Cancer Centre, Beilinson Hospital and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer Treat Rev. 2018 Nov;70:138-143. doi: 10.1016/j.ctrv.2018.08.009. Epub 2018 Aug 24.
Hormone receptor positive breast cancer is characterized by a prolonged risk of recurrence. Extended adjuvant endocrine therapy improves disease-free survival (DFS), but no effect on overall survival has been observed. This may be explained by changes in the relative contribution of local, regional and distant recurrences as well as non-breast cancer death to DFS events over time.
We reviewed sequential reports of large, randomized, adjuvant endocrine therapy trials extracting the number and types of recurrences defining DFS events at each point over follow-up. Meta-regression was performed to explore the relative contribution of contralateral, loco-regional and distant recurrences as well as non-breast cancer death to DFS over time.
Analysis included 17 reports of 6 trials reporting outcomes between 28 and 120 months of follow-up. Over time, there was increasing contribution of contralateral breast cancer (5% of events at 20 months to 12% at 120 months; β = 0.663, p = 0.004) and non-breast cancer death (20% of events at 20 months to 32% at 120 months; β = 0.581, p = 0.01). There was a non-significant reduction in the contribution of distant recurrence (57% of events at 20 months to 45% at 120 months; β = -0.397, p = 0.11), but no change in loco-regional recurrence (18% of events at 20 months to 11% at 120 months; β = -0.301, p = 0.30).
With increasing follow-up, DFS events are increasing defined by contralateral recurrence and non-breast cancer deaths with a trend for fewer distant recurrences. This may explain the limited association between DFS and overall survival with extended adjuvant endocrine therapy.
激素受体阳性乳腺癌的特点是复发风险持续时间长。延长辅助内分泌治疗可改善无病生存期（DFS），但未观察到对总生存期的影响。这可能是由于随着时间的推移，局部、区域和远处复发以及非乳腺癌死亡对 DFS 事件的相对贡献发生了变化。
我们回顾了大型、随机、辅助内分泌治疗试验的连续报告，从中提取出每个随访时间点定义 DFS 事件的复发数量和类型。进行了荟萃回归分析，以探讨随着时间的推移，对侧、局部区域和远处复发以及非乳腺癌死亡对 DFS 的相对贡献。
分析包括 6 项试验的 17 份报告，报告的随访时间为 28 至 120 个月。随着时间的推移，对侧乳腺癌的贡献逐渐增加（20 个月时为 5%的事件，120 个月时为 12%；β=0.663，p=0.004），非乳腺癌死亡的贡献也逐渐增加（20 个月时为 20%的事件，120 个月时为 32%；β=0.581，p=0.01）。远处复发的贡献呈非显著性降低（20 个月时为 57%的事件，120 个月时为 45%；β=-0.397，p=0.11），但局部区域复发无变化（20 个月时为 18%的事件，120 个月时为 11%；β=-0.301，p=0.30）。
随着随访时间的延长，DFS 事件的定义逐渐由对侧复发和非乳腺癌死亡所主导，远处复发的趋势逐渐减少。这可能解释了延长辅助内分泌治疗与无病生存期和总生存期之间的关联有限。
