Abstract

Background & objectives: Presence of TILs in breast cancer indicates better therapeutic responses to neoadjuvant chemotherapy (NAC), increased pCR and improved outcome. We aim at evaluation of TILs in breast cancer biopsies in correlation with pathological response after NAC in locally advanced breast cancer Methods. This study was conducted at Ain Shams university hospital and Maadi Military hospital in Egypt. 45 Female patients with locally advanced breast cancer were treated with NAC; pathological response was assessed. Tumours were categorized into: luminal A, luminal B, Her2 enriched and TNBC. Assessment of TILs (CD4 and CD8 lymphocytes) was based on Immuno-Oncology Biomarker Working Group guidelines. Results: Tumours were classified into high and low TIL groups using the interquartile range cutoff (29%). High CD4 group showed increased pCR (p = 0.003) and smaller residual tumours (p = 0.04). High CD8 group showed a significant association with smaller residual tumours (p = 0.003). At follow-up of 24-months, CD4 and CD8 high groups showed significantly higher 2-years DFS. The difference between CD4 high and low groups was significant in regards to estrogen receptor status, showing higher levels in hormone-negative tumors (p = 0.029). Patients with Her2 subtype showed higher CD4 (p = 0.007) and CD8 expression (p = 0.018). In CD4 & CD8 low groups, more patients developed local recurrence and distant metastasis (p = 0.025). Conclusion: We concluded that TILs may predict response to NAC and overall prognosis of breast cancer. The evaluation of TILs in correlation with morphological or genomics-based parameters helps to stratify patients of breast cancer.

Highlights

  • Neoadjuvant chemotherapy is increasingly used for the treatment of breast cancer aiming at reduction of the tumor size, allowing conservative surgical resection, eliminating clinically silent metastatic foci, and providing prognostic data based on the pathologic response of the tumor [1]

  • In the current trial we investigated the correlation between tumor-infiltrating lymphocytes (TILs) and the response to neoadjuvant chemotherapy in locally advanced breast cancer cases in Egyptian females

  • We concluded that presence of high TILs levels may identify a group of patients with excellent prognosis

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Summary

Introduction

Neoadjuvant chemotherapy is increasingly used for the treatment of breast cancer aiming at reduction of the tumor size, allowing conservative surgical resection, eliminating clinically silent metastatic foci, and providing prognostic data based on the pathologic response of the tumor [1].Evidence is emerging that pathological response after neoadjuvant chemotherapy, represented by total or near total destruction of the tumor in the surgical specimen, is believed to be a strong predictor for survival and an indicator of favourable overall prognosis [2].The tumorigenesis of breast cancer is determined by genetic alterations, phenotypic variations of cancer cells and interaction between the tumor cells and the surrounding microenvironment. Presence of TILs in breast cancer indicates better therapeutic responses to neoadjuvant chemotherapy (NAC), increased pCR and improved outcome. We aim at evaluation of TILs in breast cancer biopsies in correlation with pathological response after NAC in locally advanced breast cancer Methods. 45 Female patients with locally advanced breast cancer were treated with NAC; pathological response was assessed. High CD4 group showed increased pCR (p = 0.003) and smaller residual tumours (p = 0.04). High CD8 group showed a significant association with smaller residual tumours (p = 0.003). At follow-up of 24-months, CD4 and CD8 high groups showed significantly higher 2-years DFS. The difference between CD4 high and low groups was significant in regards to estrogen receptor status, showing higher levels in hormone-negative tumors (p = 0.029).

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