Triple Negative Breast Cancer: From Mechanisms to Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 827

Special Issue Editors


E-Mail Website
Guest Editor
Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
Interests: breast diagnostic pathology; breast molecular pathology; digital pathology and artificial intelligence (AI) in pathology

E-Mail Website
Guest Editor
1. Novazoi Theranostics, Inc., Salt Lake City, UT 84105, USA
2. Department of Science, Rowland Hall, Salt Lake City, UT 84102, USA
Interests: triple-negative breast cancer; racial disparities in breast cancer outcomes; centrosome amplification and clustering; cell cycle regulation

Special Issue Information

Dear Colleagues,

It has been known for several years that the descriptor “Triple negative breast cancer (TNBC)” is a catch-all phrase for a constellation of distinct disease entities that share in common an absence of ER and PR expression and lack amplification of the HER2 gene. The prohibitive intra-tumoral and inter-tumor heterogeneity that typifies this group of breast tumors has also made the stratification of TNBC into biomarker-positive actionable subgroups a critical step that drives treatment decisions. Thus, deciphering the tumor biology and understanding the molecular vulnerabilities for various TNBC subgroups, right-sizing systemic therapies, and improving risk stratification (beyond residual disease burden and extent) are crucial, alongside advancements in drug discovery and development, for identifying optimal precision treatments, both in neoadjuvant and adjuvant settings.

For this Special Issue, we welcome original research papers and review articles focused on promising mechanism-informed therapies for TNBC, including, but not limited to, the following:

  • HER2- and TROP2- based antibody-drug conjugates;
  • Novel immune checkpoint inhibitors;
  • Molecules targeting dsDNA repair pathways;
  • Inhibitors of cell cycle regulators;
  • Angiogenesis inhibitors;
  • Agents that target microtubule dynamics;
  • Agents that target centrosome clustering pathways;
  • Notch pathway and FGFR inhibitors;
  • EGFR inhibitors;
  • PIK3K/AKT/mTOR inhibitors;
  • Epigenetic modifiers;
  • Monoclonal antibodies;
  • Therapeutic vaccines;
  • Endocrine therapies;
  • Chemotherapies.

Dr. Emad Rakha
Dr. Padmashree Rida
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • triple-negative breast cancer
  • neoadjuvant
  • adjuvant
  • chemotherapy
  • immunotherapy
  • antibody–drug conjugates
  • immune checkpoint inhibitors
  • DNA damage
  • EGFR
  • FGFR
  • microtubule dynamics
  • centrosome amplification

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

10 pages, 953 KiB  
Article
Clinical Significance of Tumor Grade in Triple-Negative Breast Cancer: A Retrospective Cohort Analysis
by Neya Ramanan, Mah-noor Malik, Sarang Upneja, Haniya Farooq, Swati Kulkarni, Rasna Gupta, John Mathews, Abdullah Nasser, Alina Bocicariu, Laurice Arayan, Lisa Porter, Bre-Anne Fifield, Rong Luo, Muriel Brackstone and Caroline Hamm
Biomedicines 2025, 13(5), 1100; https://doi.org/10.3390/biomedicines13051100 - 1 May 2025
Viewed by 148
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 [...] Read more.
Triple-negative breast cancer (TNBC) is a heterogeneous cancer that lacks estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) proteins. Here, we investigated the prognostic value of grade in patients with TNBC. Methods: This retrospective study analyzed 780 TNBC patients from two large regional cancer programs in Canada. Patients seen between 1 January 2004 and 31 December 2022 were included. Patients with grade 1 tumors and stage IV disease were excluded from analysis. Demographic information regarding the patient, tumor, and treatment were collected. The primary outcomes, relapse-free survival (RFS) and overall survival (OS), were analyzed using the Cox proportional hazards model and max-combo test. Results: For patients with grade 2 TNBC, median RFS was 14.1 years (95% CI, 9.48 to not reached (NR)) while it was not reached for patients with grade 3 tumors. No difference for relapse was identified in the first five years. Beyond 5 years, 4.9% of the patients with grade 2 tumors and 1.6% of those with grade 3 tumors relapsed (p = 0.006). In that same study period, 10.4% of patients with grade 2 tumors and 5.7% of those with grade 3 tumors died (p = 0.03). Conclusion: Grade 2 TNBC was associated with a higher risk of relapse and death after the 5-year mark compared to grade 3 TNBC. This distinct pattern of relapse and survival in grade 2 TNBC, characterized by an increased risk of relapse and mortality after 5 years, warrants confirmatory investigations. Full article
Show Figures

Figure 1

22 pages, 7330 KiB  
Article
Relevance of Cellular Homeostasis-Related Gene Expression Signatures in Distinct Molecular Subtypes of Breast Cancer
by Sharda P. Singh, Chathurika S. Dhanasekara, Michael W. Melkus, Chhanda Bose, Sonia Y. Khan, Flavia Sardela de Miranda, Maria F. Mahecha, Prrishti J. Gukhool, Sahil S. Tonk, Se-Ran Jun, Sahra Uygun and Rakhshanda Layeequr Rahman
Biomedicines 2025, 13(5), 1058; https://doi.org/10.3390/biomedicines13051058 - 28 Apr 2025
Viewed by 237
Abstract
Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and [...] Read more.
Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I–III breast cancer patients across 90 institutions in the United States and stratified risk groups based on a 70-gene signature (MammaPrint®-MP) and molecular subtype based on an 80-gene signature (BluePrint®-BP). This study aimed to identify the gene expression patterns and biomarkers associated with breast cancer risk and progression by integrating transcriptomic and clinical data. Methods: Targeted 111 unique gene expression and clinical data points from 978 breast cancer samples, representing each BP subtype (26% Luminal A, 26% Luminal B, 25% Basal, 23% HER2), obtained from Agendia Inc. These genes were selected based on their involvement in the mercapturic acid pathway, white and brown adipose tissue markers, inflammation markers, tumor-associated genes, apoptosis, autophagy, and ER stress markers. All statistical analyses, including principal component analysis (PCA), were performed using R version [4.4.0]. Prognostic values and genetic alterations were investigated using various web-based programs as described in the Methods section. Results: PCA of gene expression data revealed distinct clustering patterns associated with risk categories and molecular subtypes, particularly with principal component 4 (PC4). Genes related to oxidative stress, autophagy, apoptosis, and histone modification showed altered expression across risk categories and molecular subtypes. Key differentially expressed genes included SOD2, KLK5, KLK7, IL8, GSTM1/2, GLI1, CBS, and IGF1. Pathway analysis highlighted the enrichment of processes related to autophagy, cellular stress response, apoptosis, glutathione metabolism, deacetylation, and oxidative stress in high-risk and basal-like tumors compared with Ultralow and Luminal A tumors, respectively. Conclusions: This study identified gene expression signatures associated with breast cancer risk and molecular subtypes. These findings provide insights into the biological processes that may drive breast cancer progression and could inform the development of prognostic biomarkers and personalized therapeutic strategies. Full article
Show Figures

Figure 1

Back to TopTop