# Predictive Factors of Response to Neoadjuvant Chemotherapy (NACT) and Immune Checkpoint Inhibitors in Early-Stage Triple-Negative Breast Cancer Patients (TNBC)

**Authors:** Khashayar Yazdanpanah Ardakani, Francesca Fulvia Pepe, Serena Capici, Thoma Dario Clementi, Marina Elena Cazzaniga

PMC · DOI: 10.3390/curroncol32070387 · 2025-07-04

## TL;DR

This paper investigates factors that can predict how early-stage triple-negative breast cancer patients respond to chemotherapy and immune treatments, aiming to improve personalized treatment strategies.

## Contribution

The study identifies and evaluates multiple predictive biomarkers for treatment response in triple-negative breast cancer patients.

## Key findings

- Tumor-infiltrating lymphocytes, circulating tumor DNA, and p53 status may predict treatment response in TNBC patients.
- Factors like Ki-67 and circulating tumor cells could help guide personalized treatment approaches.

## Abstract

Triple-negative breast cancer (TNBC) is a type of breast cancer very aggressive. Scientific efforts are undergoing trying to better understand how each person’s cancer might respond to treatment, before starting therapy. Currently, the main treatment combines chemotherapy with drugs that help the immune system fight cancer. We looked at several factors that might help response prediction, like immune cells inside the tumor, cancer cells or DNA detected in patients’ blood, a gene called p53 and a marker called Ki-67 which represents cancer growing. By studying these factors, the goal is to personalize treatment and improve outcomes for people with TNBC.

Triple-negative breast cancer (TNBC) is a heterogenous group of breast tumors. This type of breast tumor is relatively difficult to manage, due to the lack of expression of Hormone Receptors (HR) and human epidermal growth factor receptor (HER2). Efforts have been made to understand the factors involved in determining how a triple-negative breast tumor responds to therapy. The standard of treatment in most cases today is a combined modality of immune checkpoint inhibitors (ICIs) and chemotherapy with agents such as anti-mitotic (taxanes) or DNA-damaging agents (alkylating agents, cyclophosphamides, platin salts). In this study, we investigated the predictive and prognostic factors for TNBC, in the neoadjuvant setting; understanding each patient’s response before treatment initiation is crucial to guiding the subsequent approach and finally improving patient outcomes. We focused on tumor-infiltrating lymphocytes at the site of the primary tumor (TILs), circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), the mutational status of protein 53 (p53), and Ki-67, investigating the potential roles of these factors in predicting responses to anti-cancer agents.

## Linked entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157]
- **Chemicals:** taxanes (PubChem CID 78384800)
- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}
- **Diseases:** cancer (MESH:D009369), breast tumor (MESH:D001943), TNBC (MESH:D064726)
- **Chemicals:** cyclophosphamides (MESH:D003520), platin salts (-), taxanes (MESH:D043823)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12294045