Background: Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. Methods: We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. Results: We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n= 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42–0.92;p= 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53–1.62;p= 0.785) and BCSS (OR = 1.04; CI-95%: 0.45–2.41;p= 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59–1.22;p= 0.369) (BCSS: OR = 0.72; CI-95%: 0.38–1.36;p= 0.305). Conclusion: Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.
背景：多项随机试验已证实，辅助内分泌治疗（ET）联合全乳放疗（WBI）是早期乳腺癌保乳手术（BCS）后的标准治疗方案。多项研究探讨了省略WBI的治疗策略，结果显示该方案虽能维持生存率但会降低局部控制效果，因此已被多部指南采纳为特定患者的治疗选择。鉴于ET与WBI具有截然不同的副作用特征，省略ET而非WBI同样可能成为有价值的替代方案。然而，目前尚未对BCS+ET与BCS+WBI的临床结局进行系统分析。 方法：我们通过系统性文献检索，筛选出2000年后发表的、针对低风险乳腺癌患者比较BCS+ET与BCS+WBI疗效的随机试验。排除标准包括使用任何形式化疗、区域淋巴结放疗及乳房切除术的研究。采用两步法进行荟萃分析：首先提取所有已发表的事件发生率及效应值，涵盖总生存期（OS）、乳腺癌特异性生存期（BCSS）、局部复发（LR）与区域复发、无病生存期、无远处转移间期、对侧乳腺癌、非乳腺癌二次原发癌及无乳房切除间期等终点指标，并通过网状荟萃分析进行比较；其次，利用早期乳腺癌试验协作组（EBCTCG）发布的个体患者数据，对OS与BCSS进行对比验证。 结果：共纳入三项直接比较BCS+ET与BCS+WBI的研究（n=1059），以及九项额外设置BCS单用组和BCS+WBI+ET组的多臂研究（总随机化患者7207例），形成四组比较。网状分析显示，BCS+WBI组的LR显著低于BCS+ET组（HR=0.62；95%CI：0.42–0.92；p=0.019）。两组在OS（HR=0.93；95%CI：0.53–1.62；p=0.785）与BCSS（OR=1.04；95%CI：0.45–2.41；p=0.928）方面未见显著差异。此外，BCS+WBI组的无远处转移间期较短，对侧乳腺癌发生率较高，无乳房切除间期较短。基于EBCTCG数据的分析表明，BCS+ET与BCS+WBI在10年随访期的OS（OR=0.85；95%CI：0.59–1.22；p=0.369）与BCSS（OR=0.72；95%CI：0.38–1.36；p=0.305）均无显著差异。 结论：直接与间接比较证据表明，对于低风险乳腺癌患者，BCS+WBI可能成为与BCS+ET等效的降阶梯治疗策略。两种方案的不良事件及生活质量指标仍需进一步比较研究。
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