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Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy

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Abstract

Introduction

Tumor-infiltrating lymphocytes (TILs) are gaining recognition as an important immunological biomarker with therapeutic potential in breast cancer. In this cohort study conducted on patients with advanced breast cancer treated with primary systemic therapy (PST), the TILs concentration was correlated with response to PST and survival outcomes.

Methods

Patients with primary breast cancer treated with PST between 2016 and 2020 were included in this study, approved by IEC, and registered on ClinicalTrials.gov (NCT05250336). Tumor core biopsies obtained prior to starting treatment from 489 patients were assessed for the proportion of stromal TILs by standardized method and categorized into low (0–10% immune cells), intermediate (11–59%), and high (≥ 60%) TILs. TIL concentration and complete pathological response (pCR), disease-free survival (DFS), and overall survival (OS) were correlated.

Results

Of the 489 patients, 372 matched the eligibility criteria for assessment of TILs and made the final study cohort. Among these, 135 were luminal, 129 HER2-enriched, and 108 triple-negative breast cancers (TNBC). Proportions of patients with high TILs were greater in TNBC (15.7%) and HER2-enriched (9.3%), compared to luminal cancers (4.4%). High TIL concentration was correlated with higher pCR in all subtypes. A pCR was achieved in 33.3, 50, and 52.9% of high TIL patients in luminal, HER2-enriched, and TNBC subtypes, respectively (p < 0.05). High TILs were linked to longer DFS and OS in TNBC and HER2-enriched breast cancers.

Conclusion

In this first study of its kind from a low- and middle-income country, high TILs concentration was found to be a predictor of response to PST across all breast cancer subtypes. TILs concentration was found predictive of better DFS and OS in TNBC and HER2-enriched cancers. Prognostic role of TILs in luminal cancers was not so apparent.

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Acknowledgements

This research was supported by an intramural research grant from the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India (A-12-PGI/IMP/79/2018 to Dr. Gaurav Agarwal). The funding source had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, writing assistance, or decision to submit results. The authors thank all the investigators and collaborators who contributed to this study.

Funding

Supported by SGPGI Intramural research grant (A-12-PGI/IMP/79/2018).

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Author notes

  1. Gaurav Agarwal and K. M. M. Vishvak Chanthar contributed equally to this work and are joint first authors.

Authors and Affiliations

  1. Department of Endocrine and Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226014, India

    Gaurav Agarwal, K. M. M. Vishvak Chanthar, M. Sabaretnam, Gyan Chand & Anjali Mishra

  2. Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

    Shweta Katiyar, Niraj Kumari & Narendra Krishnani

  3. Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

    Punita Lal

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  1. Gaurav Agarwal
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Correspondence to Gaurav Agarwal.

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Institutional ethics committee clearance reference no. 2018–177-IMP-EXP-4.

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Agarwal, G., Vishvak Chanthar, K.M.M., Katiyar, S. et al. Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy. World J Surg 47, 1238–1246 (2023). https://doi.org/10.1007/s00268-023-06912-x

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