根据分子亚型评估肿瘤浸润淋巴细胞(TIL)对预测乳腺癌新辅助化疗(NAC)疗效的价值

The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes.

作者信息

Faur Ionut Flaviu, Dobrescu Amadeus, Clim Adelina Ioana, Pasca Paul, Prodan-Barbulescu Catalin, Gherle Bogdan Daniel, Tarta Cristi, Isaic Alexandru, Brebu Dan, Duta Ciprian, Totolici Bogdan, Lazar Gabriel

机构信息

IInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, Romania.

X Department of General Surgery, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.

出版信息

Biomedicines. 2023 Nov 13;11(11):3037. doi: 10.3390/biomedicines11113037.

Abstract

INTRODUCTION

The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients treated with neoadjuvant chemotherapy (NAC) has increased and the identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority.

MATERIALS AND METHODS

We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020-2022 at the Ist Clinic of Oncological Surgery, Oncological Institute "Prof Dr I Chiricuta" Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts were performed using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG).

RESULTS

There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype and the number of mitoses ( < 0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis ( < 0.005). We also demonstrated that high pre-NAC STIL represents a strong predictive marker for pCR.

CONCLUSION

This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of sTIL as a novel predictive and therapy-predicting factor should become a routinely performed analysis that could guide clinicians when choosing the most appropriate therapy.

摘要

引言

抗肿瘤宿主免疫反应是乳腺癌中的一个重要因素,但其作用尚未完全明确。近年来,肿瘤浸润淋巴细胞(TIL)作为乳腺癌免疫生物标志物的作用已得到大量研究。接受新辅助化疗(NAC)的患者数量不断增加,因此识别预测病理完全缓解(pCR)概率的生物标志物成为当务之急。

材料与方法

我们评估了2020年至2022年在克卢日-纳波卡市“伊斯特·奇里库塔教授”肿瘤研究所第一肿瘤外科诊所接受NAC治疗并随后进行手术切除的334例乳腺癌患者。其中,122例患者的NAC前活检组织和NAC后切除组织均可进行组织学评估。活检切片和切除组织均采用苏木精-伊红(H&E)染色进行评估。TIL评估按照国际TIL工作组(ITILWG)的建议进行。

结果

NAC前TIL水平升高之间存在强关联。同时发现,基质TIL与肿瘤分级、淋巴结转移数量、分子亚型及有丝分裂数量之间存在显著统计学相关性(<0.005)。瘤内TIL与肿瘤大小、远处转移、分子亚型、有丝分裂数量、分期及淋巴结转移之间存在显著相关性(<0.005)。我们还证明,NAC前高基质TIL是pCR的强预测标志物。

结论

本研究揭示了TIL作为乳腺癌预测生物标志物的作用,不仅适用于公认的三阴性乳腺癌(TNBC)和HER2过表达(HER2+)亚型,也适用于Luminal A和B分子亚型。在这种情况下,将sTIL评估作为一种新的预测和治疗预测因素应成为常规分析,可为临床医生选择最合适的治疗方法提供指导。

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