Immunotherapy for triple-negative breast cancer: current trends and future prospects - Review

Sep 23, 2026

Triple-negative breast cancer (TNBC) represents 10–20% of all breast cancers and is marked by tumor heterogeneity, high aggressiveness, poor prognosis, and frequent recurrence. Immune checkpoint inhibitors (ICIs) in hematologic and solid malignancies can strengthen long-term survival and maintain anti-tumor activity. In TNBC, abundant intra-tumoral tumor-infiltrating lymphocytes (TILs) and stromal immune cells reflect heightened immune activity, serving as a prognostic marker and suggesting improved immunotherapy responsiveness. This narrative review outlines current TNBC immunotherapy strategies across disease stages, including rationale, clinical application, and biomarker challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Introduction

Immunotherapy as a treatment option in TNBC

Immune checkpoint inhibitors and mechanism

Immune checkpoint inhibitors as monotherapy

Biomarkers and patient selection

Essalihi et al. Journal of the Egyptian National Cancer Institute (2025) 37:51 [https://doi.org/10.1186/s43046-025-00295-x](https://doi.org/10.1186/s43046-025-00295-x) Journal of the Egyptian National Cancer Institute NARRATIVE REVIEW Open Access Immunotherapy for triple-negative breast cancer: current trends and future prospects Amina Essalihi 1* , Oumaima Bouchra 1, Khadija Khadiri2, Zineb Khadrouf2 and Mehdi Karkouri 1,3 Abstract Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers. These tumors are heterogeneous, highly aggressive, and associated with a poor prognosis and a high risk of recurrence. In both hematologic and solid malignancies, immune checkpoint inhibitors (ICIs) have demonstrated the ability to enhance long-term survival and sustain robust anti-tumor responses. Immunotherapy has also been introduced as a treatment option forTNBC, a subtype characterized by a high presence of intra-tumoral tumor-infiltrating lymphocytes (TILs) and stromal immune cells. This heightened immune activity within TNBC serves as a prognostic marker, indicating a potential for better responses to immunotherapy due to increased tumor immune infiltration. This review provides an overview of the current landscape of immunotherapy inTNBC, exploring its rationale and application across different disease stages. Trial registration NCT02555657 . Keywords Immunotherapy, Triple-negative breast cancer, Immune checkpoint inhibitors, Clinical Trials, PDL-1, Tumorinfiltrating lymphocytes Introduction Breast cancers are classified into different subcategories to guide their management. Triple-negative breast cancer (TNBC) is diagnosed when no known marker responsive to targeted therapy is identified [1]. It is characterized by the absence of human epidermal growth factor receptor 2 (HER2) overexpression/amplification, as well as the absence of estrogen receptors (ER) and progesterone receptors (PR) [2]. These cancers, which represent approximately 10–20% of all breast cancers, are highly aggressive, and the current treatment options remain insufficiently effective [3, 4]. *Correspondence: Amina Essalihi [amina.essalihi-etu@etu.univh2c. ma](amina.essalihi-etu@etu.univh2c. ma) 1 Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca, Morocco 2 Laboratory of Immunology and Biodiversity, Faculty of Sciences, Aïn Chock, Hassan II University of Casablanca, Casablanca, Morocco 3 Pathology Department, University Hospital Ibn Rochd, Casablanca, Casablanca, Morocco The management of TNBC relies on locoregional treatments such as surgery and radiotherapy. Additionally, neoadjuvant chemotherapy (NACT) is frequently used for larger tumors to facilitate breast-conserving surgery [5]. However, despite chemotherapy (CHT) intervention, TNBC remains associated with early recurrence and high morbidity. Compared to HER2-positive and hormone receptor-positive breast tumors, TNBC patients continue to have poorer prognoses [6]. Immunotherapy has emerged as a potential new therapeutic option for TNBC patients. Programmed deathligand 1 (PD-L1) is a key immune checkpoint protein that helps regulate immune responses. Checkpoint inhibitors (ICIs), a type of immunotherapy, work by blocking PD-L1, thereby preventing cancer cells from evading immune system attacks [5]. Checkpoint blockade in melanoma has been highly successful, prompting the investigation of these agents in other malignancies, including TNBC [7] . © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in thi

FAQs

What distinguishes triple-negative breast cancer for treatment planning?

TNBC is defined by the lack of HER2 overexpression/amplification and the absence of estrogen and progesterone receptors. It also lacks effective targeted therapy markers, contributing to limited treatment options.

How do immune checkpoint inhibitors (ICIs) work in TNBC?

ICIs block immune checkpoint signaling, particularly PD-L1, preventing cancer cells from evading immune attacks. This can enhance anti-tumor immune responses.

Which biomarkers are discussed as predictors of immunotherapy response in TNBC?

The review highlights tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and tumor mutational burden (TMB) as key factors. It also stresses the growing need for reliable predictive biomarkers for precision immunotherapy.

Sep 23, 2026

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