三阴性乳腺癌（TNBC）占所有乳腺癌的15-20％，与更高的复发和远处转移率相关联。早期TNBC的标准治疗是联合环磷酰胺（AC）的蒽环类药物，然后是紫杉醇，在新辅助或辅助设置中。本研究旨在在TNBC的患者源异种移植（PDX）模型中确定AC反应的预测性生物标志物，并在临床环境中对其进行验证。通过对具有不同AC反应的39个PDX进行基因和蛋白表达分析，我们发现高表达HORMAD1与更好的AC反应相关。基因和蛋白表达均与启动子低甲基化相关。在526名乳腺癌患者中，TNBC中71％的患者过度表达HORMAD1。在186名接受AC治疗的TNBC患者的第二组中，HORMAD1表达与更长的无转移生存期（MFS）相关。总之，HORMAD1过表达预测了PDX对AC的改善反应，并且是接受AC治疗的TNBC患者的独立预后因素。©2023 John Wiley＆Sons Ltd代表欧洲生化联合会发表的《分子肿瘤学》。

Triple negative breast cancers (TNBCs) represent 15-20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo-adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers of AC response in patient-derived xenograft (PDX) models of TNBC and to validate them in the clinical setting. By gene and protein expression analysis of 39 PDX with different responses to AC, we found that high expression of HORMAD1 was associated with better response to AC. Both gene and protein expression were associated with promoter hypomethylation. In a cohort of 526 breast cancer patients, HORMAD1 was over-expressed in 71% of TNBC. In a second cohort of 186 TNBC patients treated with AC, HORMAD1 expression was associated with longer metastasis-free survival (MFS). In summary, HORMAD1 overexpression was predictive of an improved response to AC in PDX and is an independent prognostic factor in TNBC patients treated with AC.© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.