Baez-Navarro Ximena, van den Ende Nadine S, Nguyen Anh H, Sinke Renata, Westenend Pieter, van Brakel Johannes Bastiaan, Stobbe Claudia, Westerga Johan, van Deurzen Carolien H M
Department of Pathology, Erasmus University Medical Center, 3015 GD, Rotterdam, The Netherlands.
Department of Pathology, HMC, The Hague, The Netherlands.
Breast Cancer Res. 2024 Mar 11;26(1):41. doi: 10.1186/s13058-024-01783-z.
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.
大多数三阴性乳腺癌（TNBC）患者不适合接受靶向治疗，化疗仍是主要的治疗选择。近年来，免疫疗法因其免疫原性在TNBC治疗中显示出了有前景的效果。此外，一种新型抗体药物偶联物，即曲妥珠单抗-德卢替康，已在HER2低表达（HER2-low）的TNBC患者中显示出疗效。这些新型治疗方案引发了关于基质肿瘤浸润淋巴细胞（sTILs）密度与HER2表达水平之间潜在关联的问题。我们旨在评估TNBC患者中HER2表达水平（HER2-low与HER2-0）与sTILs密度之间的关联，以及它们如何影响新辅助化疗（NAC）的疗效。这是一项回顾性多中心研究，纳入了2018年至2022年间确诊的所有TNBC患者。中心病理评估包括sTILs百分比和HER2表达水平。肿瘤被重新分类为HER2-0（HER2免疫组化0）或HER2-low（免疫组化1+或2+且阴性反射试验）。比较了HER2-0和HER2-low病例之间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753例TNBC患者，其中292例接受了NAC。原始病理报告与中心评估之间的观察者间一致性为中等（77%在重新分类为HER2-0或HER2-low后具有相同的免疫组化状态；k = 0.45）。HER2-low的TNBC约占肿瘤的三分之一（36%）。HER2-0和HER2-low病例之间在sTILs密度或完全病理缓解率方面未发现显著差异（分别为p = 0.476和p = 0.339）。sTILs密度（≥10% sTILs与<10%）与达到完全病理缓解（pCR）独立相关（p = 0.011）。总之，未发现HER2-low状态与sTILs密度及对NAC的反应之间存在显著关联。尽管如此，sTILs可能是预测TNBC患者NAC反应的独立生物标志物。
