Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Aging (Albany NY). 2021 Aug 10;13(15):19835-19866. doi: 10.18632/aging.203395.
We assessed the effect of bisphosphonates (BPs) on breast cancer (BCa) patient survival and explored how long the effect can persist after treatment.
We performed a meta-analysis and trial sequential analysis (TSA) of prospective studies including randomized controlled trials (RCTs) and cohort studies. We performed extensive sensitivity analyses to assess the robustness of the findings.
Seventeen RCTs and eight cohorts with 81508 BCa patients were identified. A significant beneficial effect of BPs on BCa survival was found (RR, 0.725; 95% CI, 0.627-0.839), and the TSA results also suggested firm evidence for this beneficial effect. Both summarized results from RCTs and cohorts provided firm evidence for this effect, although the effect estimates were stronger from cohorts than RCTs (RR, 0.892; 95% CI, 0.829-0.961; 0.570; 95% CI, 0.436-0.745; respectively). This beneficial effect was confirmed for bone-metastases (RR, 0.713; 95% CI, 0.602-0.843) and postmenopausal women (RR, 0.737; 95% CI, 0.640-0.850). Importantly, our results demonstrated that this beneficial effect was retained at least 1-2 years after treatment completion (RR, 0.780; 95% CI, 0.638-0.954) and could persist for up to more than 4 years after treatment completion (RR, 0.906; 95% CI, 0.832-0.987). Extensive sensitivity analyses showed the robustness of our results. The GRADE quality of evidence was generally judged to be moderate to high.
The present study provides firm evidence for a significant beneficial effect of BPs on BCa survival in patients with early-stage BCa, and this effect was retained at least 1-2 years after BP treatment completion.
我们评估了双膦酸盐（BPs）对乳腺癌（BCa）患者生存的影响，并探讨了治疗后这种影响能持续多久。
我们对包括随机对照试验（RCTs）和队列研究在内的前瞻性研究进行了荟萃分析和试验序贯分析（TSA）。我们进行了广泛的敏感性分析，以评估研究结果的稳健性。
共纳入了 17 项 RCT 和 8 项队列研究，包含 81508 例 BCa 患者。结果显示 BPs 对 BCa 生存有显著的有益影响（RR，0.725；95%CI，0.627-0.839），且 TSA 结果也提示这种有益影响有确凿证据。RCT 和队列研究的综合结果均提供了这种影响的确凿证据，尽管队列研究的效应估计值强于 RCT（RR，0.892；95%CI，0.829-0.961；RR，0.570；95%CI，0.436-0.745）。这种有益影响在骨转移（RR，0.713；95%CI，0.602-0.843）和绝经后妇女（RR，0.737；95%CI，0.640-0.850）中得到了证实。重要的是，我们的结果表明，这种有益影响至少在治疗完成后 1-2 年内仍存在（RR，0.780；95%CI，0.638-0.954），并且在治疗完成后长达 4 年以上仍能持续（RR，0.906；95%CI，0.832-0.987）。广泛的敏感性分析表明了我们研究结果的稳健性。证据质量的 GRADE 分级通常被判断为中等到高度。
本研究为 BPs 对早期 BCa 患者的 BCa 生存有显著有益影响提供了确凿证据，且这种影响在 BP 治疗完成后至少 1-2 年内仍存在。
