Ren Xinyu, Zhou Tong, Song Yu, Wu Huanwen, Chou Jeff, Miller Lance D, Liang Zhiyong, Shen Songjie
Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Oncology, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
Breast. 2025 Apr;80:103889. doi: 10.1016/j.breast.2025.103889. Epub 2025 Jan 23.
Triple-negative breast cancer (TNBC) is group of heterogeneity caner. Despite majority of them had the unfavorable prognosis, a subset of patients who do not receive chemotherapy exhibit a good prognosis. Biomarkers are required to recognize these group of pateints and improve the current therapeutic strategies for them.
A retrospective analysis of 997 patients with TNBC from three datasets including 188 case of Peking Union Medical College Hospital (PUMCH) and two TNBC datasets from published cohort studies(279 case of Affy-set, 530 case of GSE set) was conducted. Intrinsic subtypes (basal-like, immune-enhanced, human epidermal growth factor receptor-2 [HER2]-enriched and luminal A/B) and tumor environmental immunity were evaluated using expression profiles of a 72-gene panel. Association of intrinsic subtype and immunity score with distant metastasis-free survival (DMFS) and overall survival (OS) was analyzed.
Five intrinsic subtypes were identified in the patients with TNBC, comprising 64 % basal-like, 19 % immune-enhanced, 11 % HER2-enriched, 5 % luminal A, and 2 % luminal B. In the absence of adjuvant chemotherapy (ACT), Luminal A and immune-enhanced subtypes showed better DMFS than basal-like, HER2-enriched, and luminal B subtypes(P = 0.35). Significantly good OS was observed in luminal A and immune-enhanced subtypes compared to basal-like and HER2-enriched subtypes (P < 0.05). So two subtype groups were further classified as low-risk subtypes, including luminal A and immune-enhanced, and high-risk subtypes, including basal-like, HER2-enriched, and luminal B. Except for the immune-enhanced subtype, each subtype was further sorted and grouped according to immunity score, istrong and iweak. Significant improvements in both DMFS and OS were observed in patients with istrong compared with those with iweak(P = 0.01 and 0.0051 respectively). When combining intrinsic subtype and immunity status to predict the benefit from ACT, all high-risk subtype patients demonstrated improved DMFS(P = 0.075) and OS(P < 0.0001), with istrong patients exhibiting greater benefit; low-risk subtype plus iweak patients showed marginal benefit, whereas low-risk subtype plus istrong patients demonstrated least benefit from ACT.
Intrinsic subtype and immunity score is good prognostic biomarkers for patients with TNBC in the absence of chemotherapy. Combined intrinsic subtype and immunity evaluation could identify patients with TNBC who do not benefit from chemotherapy.
三阴性乳腺癌（TNBC）是一组异质性癌症。尽管大多数患者预后不良，但一部分未接受化疗的患者预后良好。需要生物标志物来识别这类患者，并改善当前针对他们的治疗策略。
对来自三个数据集的997例TNBC患者进行回顾性分析，其中包括北京协和医院（PUMCH）的188例病例以及已发表队列研究中的两个TNBC数据集（Affy-set组279例，GSE组530例）。使用72基因panel的表达谱评估内在亚型（基底样、免疫增强、人表皮生长因子受体2[HER2]富集和腔面A/B）和肿瘤微环境免疫。分析内在亚型和免疫评分与无远处转移生存期（DMFS）和总生存期（OS）的相关性。
在TNBC患者中鉴定出五种内在亚型，包括64%基底样、19%免疫增强、11%HER2富集、5%腔面A和2%腔面B。在未进行辅助化疗（ACT）的情况下，腔面A和免疫增强亚型的DMFS优于基底样、HER2富集和腔面B亚型（P = 0.35）。与基底样和HER2富集亚型相比，腔面A和免疫增强亚型的OS明显更好（P < 0.05）。因此，将两个亚型组进一步分为低风险亚型，包括腔面A和免疫增强，以及高风险亚型，包括基底样、HER2富集和腔面B。除免疫增强亚型外，根据免疫评分将每个亚型进一步分类和分组，分为免疫强（istrong）和免疫弱（iweak）。与免疫弱的患者相比，免疫强的患者在DMFS和OS方面均有显著改善（分别为P = 0.01和0.0051）。当结合内在亚型和免疫状态来预测ACT的获益时，所有高风险亚型患者的DMFS（P = 0.075）和OS（P < 0.0001）均有改善，免疫强的患者获益更大；低风险亚型加免疫弱的患者显示出边际获益，而低风险亚型加免疫强的患者从ACT中获益最少。
内在亚型和免疫评分是TNBC患者在未进行化疗时的良好预后生物标志物。结合内在亚型和免疫评估可以识别出不能从化疗中获益的TNBC患者。
