三阴性乳腺癌中的 HER2 低表达和肿瘤浸润淋巴细胞:它们之间有联系吗?

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-03-11 DOI:10.1186/s13058-024-01783-z
Ximena Baez-Navarro, Nadine S. van den Ende, Anh H. Nguyen, Renata Sinke, Pieter Westenend, Johannes Bastiaan van Brakel, Claudia Stobbe, Johan Westerga, Carolien H. M. van Deurzen
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引用次数: 0

摘要

大多数三阴性乳腺癌(TNBC)患者不适合接受靶向治疗,因此化疗成为主要的治疗选择。最近,免疫疗法因其免疫原性在 TNBC 中取得了可喜的成果。此外,一种新型抗体-药物共轭物,即曲妥珠单抗-德鲁司坦,也显示出对HER2低表达(HER2-low)的TNBC患者有效。这些新型治疗方案提出了一个问题:基质肿瘤浸润淋巴细胞(sTILs)的密度与HER2表达水平之间可能存在关联。我们的目的是评估 TNBC 患者的 HER2 表达水平(HER2-low 与 HER2-0)和 sTILs 密度之间的关联,以及它们对新辅助化疗 (NAC) 反应的影响。这是一项回顾性多中心研究,包括2018年至2022年期间确诊的所有TNBC患者。中央病理审查包括 sTILs 百分比和 HER2 表达水平。肿瘤被重新分类为HER2-0(HER2 IHC 0)或HER2-低(IHC 1 +或2 +,反射试验阴性)。比较了 HER2-0 和 HER2 低病例的各种临床病理特征,包括 sTILs 密度和对 NAC 的反应。本研究共纳入了 753 例 TNBC 患者,其中 292 例患者接受了 NAC 治疗。原始病理报告与中央复查之间的观察者间一致性为中等(77%的患者在重新分类为HER2-0或HER2-low后具有相同的IHC状态;k = 0.45)。HER2低的TNBC约占肿瘤的三分之一(36%)。HER2-0和HER2-low病例的sTILs密度和完全病理反应率无明显差异(分别为p = 0.476和p = 0.339)。sTILs的密度(≥10% sTILs vs. <10%)与获得pCR独立相关(p = 0.011)。总之,HER2-low状态与sTILs密度或对NAC的反应均无明显关联。然而,sTILs可能是预测TNBC患者NAC反应的独立生物标志物。
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HER2-low and tumor infiltrating lymphocytes in triple-negative breast cancer: Are they connected?
Most patients with triple-negative breast cancer (TNBC) are not candidates for targeted therapy, leaving chemotherapy as the primary treatment option. Recently, immunotherapy has demonstrated promising results in TNBC, due to its immunogenicity. In addition, a novel antibody–drug conjugate, namely, trastuzumab-deruxtecan, has shown effectiveness in TNBC patients with low-HER2 expression (HER2-low). These novel treatment options raise the question about the potential association between the density of stromal tumor-infiltrating lymphocytes (sTILs) and the level of HER2 expression. We aimed to evaluate the association between the level of HER2 expression (HER2-low versus HER2-0) and density of sTILs in TNBC patients, and how they impact the response to neoadjuvant chemotherapy (NAC). This was a retrospective multicenter study including all TNBC patients diagnosed between 2018 and 2022. Central pathology review included sTILs percentages and level of HER2 expression. Tumors were reclassified as either HER2-0 (HER2 IHC 0) or HER2-low (IHC 1 + or 2 + with negative reflex test). Various clinicopathologic characteristics, including sTILs density, and response to NAC were compared between HER2-0 and HER2-low cases. In total, 753 TNBC patients were included in this study, of which 292 patients received NAC. Interobserver agreement between the original pathology report and central review was moderate (77% had the same IHC status after reclassification in either HER2-0 or HER2-low; k = 0.45). HER2-low TNBC represented about one third (36%) of the tumors. No significant difference in sTILs density or complete pathologic response rate was found between HER2-0 and HER2-low cases (p = 0.476 and p = 0.339, respectively). The density of sTILs (≥ 10% sTILs vs. < 10%) was independently associated with achieving a pCR (p = 0.011). In conclusion, no significant association was found between HER2-low status and density of sTILs nor response to NAC. Nonetheless, sTILs could be an independent biomarker for predicting NAC response in TNBC patients.
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来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
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