Purpose: The MammaPrint prognostic assay categorizes breast cancers into high- and low-risk subgroups, and the high-risk group can be further subdivided into high 1 (MP-H1), and very high-risk high-2 (MP/H-2). The aim of this analysis was to assess clinical and molecular differences between the hormone receptor positive/HER2-negative (HR+) MP-H1, -H2, and triple negative (TN) MP-H1 and -H2 cancers. Experimental design: Pre-treatment gene expression data from 742 HER2 negative breast cancers enrolled in the I-SPY2 neoadjuvant trial was used. Prognostic risk categories were assigned using the MammaPrint assay. Transcriptional similarities across the 4 receptor and prognostic groups were assessed using principal component analyses and by identifying differentially expressed genes. We also examined pathologic complete response (pCR) rates and event-free survivals (EFS) by risk group. Results: Principal component analysis showed that HR+/MP-H2 tumors clustered with TN/MP-H2 cancers. Only 125 genes showed differential expression between the HR+/MP-H2 and TN/MP-H2 cancers while 1,465 genes were differentially expressed between HR+/MP-H2 and -H1. Gene set analysis revealed similarly high expression of cell cycle, DNA repair, and immune-infiltration related pathways in HR+/MP-H2 and TN/MP-H2 cancers. HR+/MP-H2 cancers also showed low estrogen receptor (ER)-related gene expression. pCR rates were similarly high in TN/MP-H2 and HR+/MP-H2 cancers (42% vs 30.5%, p=0.11), and MP-H2 cancers with residual cancer had similarly poor EFS regardless of ER status. Conclusions: In conclusion, HR+/MP-H2 cancers closely resemble TN breast cancers in transcriptional and clinical features and benefit from similar treatment strategies.

中文翻译：

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激素受体阳性 HER2 阴性/MammaPrint High-2 乳腺癌与三阴性乳腺癌非常相似


目的： MammaPrint 预后检测将乳腺癌分为高危和低危亚组，高危组可进一步细分为高危 1 （MP-H1） 和极高危高 2 （MP/H-2）。该分析的目的是评估激素受体阳性/HER2 阴性 （HR+） MP-H1、-H2 和三阴性 （TN） MP-H1 和 -H2 癌症之间的临床和分子差异。实验设计： 使用来自 I-SPY2 新辅助试验中入组的 742 例 HER2 阴性乳腺癌的治疗前基因表达数据。使用 MammaPrint 检测法分配预后风险类别。使用主成分分析和鉴定差异表达基因来评估 4 个受体组和预后组之间的转录相似性。我们还按风险组检查了病理完全缓解 （pCR） 率和无事件生存期 （EFS）。结果： 主成分分析显示 HR+/MP-H2 肿瘤与 TN/MP-H2 癌聚集。只有 125 个基因在 HR+/MP-H2 和 TN/MP-H2 癌症之间表现出差异表达，而 1,465 个基因在 HR+/MP-H2 和 -H1 之间表现出差异表达。基因集分析显示，在 HR+/MP-H2 和 TN/MP-H2 癌症中，细胞周期、DNA 修复和免疫浸润相关途径的表达同样高。HR+/MP-H2 癌症也显示出低雌激素受体 （ER） 相关基因表达。TN/MP-H2 和 HR+/MP-H2 癌症的 pCR 率同样高 （42% vs 30.5%，p=0.11），而有残留癌症的 MP-H2 癌症无论 ER 状态如何，EFS 都同样差。结论： 总之，HR+/MP-H2 癌症在转录和临床特征上与 TN 乳腺癌非常相似，并受益于相似的治疗策略。