Abstract

Purpose:We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery. Methods:This is a retrospective cohort study including 66 locally advanced hormone receptor-negative; HER2+ breast cancer patients presented between 2013 and 2015 at NCI-Cairo, Egypt. Enrolled patients had at least clinically T3 and/or node positive disease either clinically or radiologically. Metastatic workup included CT and bone scans or PET-CT. Patients with hormone receptor positive, HER2 negative, inadequate paraffin block and who lost follow up before or immediately after curative surgery were excluded. Patients were followed from breast surgery till relapse date for a minimum of 36 months. TILs and CD8 antigen were assessed on paraffin-embedded blocks using immunohistochemistry. Results:Patients with a median age of 52 years presented with clinical T3 stage (53%) and N1 stage (61%). Modified radical mastectomy was performed in 79%. Only 41% received neoadjuvant chemotherapy and 56% received trastuzumab. TILs were 50, 17 and 33% for absent, intermediate and extensive groups and CD8+ lymphocytes were present in 80% of cases. At the end of follow-up period, 23 patients (35%) were found to have disease recurrence either loco-regional (22%) or distant (78%). TILs were 14, 4 and 5% for absent, intermediate and extensive respectively; while CD8+ lymphocytes were absent in 6% and present (≥1%) in 17%. Higher DFS was recorded for patients with extensive TILs level only who received trastuzumab. Conclusion:High TILs is good prognosis in HER2 enriched breast cancer provided that patients received HER2 directed therapy. Moreover, CD8+ lymphocytes are highly representative and maybe used as an alternative for TILs. We recommend considering TILs and specifically CD8+ as one of the risk factors that predict prognosis of HER2+ breast cancer.

Highlights

  • One of the most important goals of cancer research is identification of robust prognostic and predictive markers

  • We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery

  • We aim to investigate the association between the level of stromal tumor infiltrating lymphocytes (TILs) and DFS in a group of ER andPR negative, HER-2 positive locally advanced breast cancer patients who received curative intent surgery at national cancer institute (NCI), Cairo University from 2013-2015

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Summary

Introduction

One of the most important goals of cancer research is identification of robust prognostic and predictive markers. Several studies investigated the interconnection between tumor infiltrating lymphocytes and tumor cell progression, as well as, predicting response to various anti-cancer therapies (Adams et al, 2014). Many researchers have focused on the association between presence of TILs and clinical outcome in various breast cancer subtypes. The relevant correlation has been shown among triple negative subtype, followed by the HER2 enriched breast cancer To this end, we aim to investigate the association between the level of stromal tumor infiltrating lymphocytes (TILs) and DFS (after a follow-up period of 3 years) in a group of ER andPR negative, HER-2 positive locally advanced breast cancer patients who received curative intent surgery at national cancer institute (NCI), Cairo University from 2013-2015. To study the association between the levels of TILs at time of presentation with other prognostic criteria in the same group will be studied

Materials and Methods
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C D 8 Absent C D 8 p re se n t
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