用MRI提前发现乳腺癌治疗响应质量差异，识别高复发风险人群。
Pretreatment DCE-MRI Resolves Response Quality Within Pathologic Endpoints in Neoadjuvant Breast Cancer
- 通过肿瘤增强异质性熵值划分治疗前结构状态，区分响应优劣。
- 25.1%的完全缓解患者为结构不良，复发风险高出2.87倍。
- 适用于需要精准评估疗效的乳腺癌新辅助治疗研究者。
病理完全缓解（pCR）是新辅助治疗的重要终点，但5-15%的完全缓解患者仍会复发，临床与基因组变量难以可靠预测。本研究检验了治疗前动态对比增强MRI的熵值——即肿瘤内强化异质性——是否可揭示隐藏在pCR和残留癌负荷（RCB）中的响应质量差异。在四个队列（共1,200名患者）中，预设的熵阈值定义了有利与不利的结构状态。结合病理结果，构建了四层级框架，在I-SPY1中复发风险相差4.1倍，在响应极端情况下达7.7倍。在I-SPY2中，219名完全缓解者中有55人（25.1%）为结构不良。外部HER2阳性队列（合并I-SPY1病理确认的pCR与UCSF最佳应答代理数据；n=33，10例复发）显示，不良结构与更高复发风险相关（HR=2.87，95% CI 1.38-5.96），捕获了7/10例复发，具有风险富集而非决定作用。在HER2阳性RCB-0亚组中，有利结构者复发率为12.5%，不利结构者为80.0%；Firth Cox回归保持显著关联（HR=8.13，95% CI 1.71-49.21；n=21，6例事件）。在杜克队列（n=908，76例远处复发）中，有利结构仍独立降低远处复发风险（调整后HR=0.61，95% CI 0.41-0.91）。RNA分析显示，有利结构与非重叠患者中可重复的免疫架构程序相关；上皮-间质转化（EMT）通路在有利侧富集，而不良组表现为广泛免疫抑制状态。然而全队列RNA模型对结构状态区分能力弱，无法恢复连续熵值。因此，治疗前MRI不取代pCR或RCB，而是揭示这些终点所压缩的响应质量差异，并识别出需前瞻性验证的高复发群体。
原文摘要 · Abstract (English)
Pathologic complete response (pCR) is a strong neoadjuvant endpoint, yet 5-15% of complete responders recur and clinical/genomic variables do not reliably identify them. We tested whether pretreatment dynamic contrast-enhanced MRI entropy - intratumoral enhancement heterogeneity - resolves response quality hidden within pCR and residual cancer burden (RCB). Across four cohorts (1,200 patients), a prespecified entropy threshold defined favorable and adverse structural states. Crossing structure with pathology yielded a four-tier framework spanning 4.1-fold recurrence in I-SPY1 and 7.7-fold at response extremes. In I-SPY2, 55 of 219 complete responders (25.1%) were structurally adverse, pretreatment. In an external HER2-positive responder synthesis (I-SPY1 pathology-confirmed pCR plus UCSF best-response proxy; n = 33, 10 events), adverse structure was associated with higher recurrence risk (HR = 2.87, 95% CI 1.38-5.96) capturing 7 of 10 recurrences, enriching rather than determining risk. In a HER2-positive RCB-0 subset, recurrence was 12.5% with favorable and 80.0% with adverse structure; Firth Cox regression preserved the association (HR = 8.13, 95% CI 1.71-49.21; n = 21, 6 events). In Duke (n = 908; 76 events), favorable structure remained independently associated with lower distant-recurrence risk (adjusted HR = 0.61, 95% CI 0.41-0.91). RNA linked favorable structure to a directionally reproduced immune-architecture program among non-overlapping patients within ISPY2; EMT-pathway enrichment was favorable-side, while the adverse tier contained a broadly immune-depleted substate. Yet full-cohort RNA models weakly discriminated structural state and did not recover continuous entropy. Pretreatment MRI therefore does not replace pCR or RCB; it reveals response-quality differences that these endpoints compress and identifies a recurrence-enriched group for prospective validation.
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