Triple-Negative Breast Cancer: Genetic Vulnerabilities and Emerging Targets for Precision Oncology

Topic Information

Dear Colleagues,

Triple-negative breast Cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer characterized by the absence of estrogen and progesterone receptors and HER2 amplification. This biological profile is associated with poor prognosis, high recurrence rates, and limited therapeutic options. Recent advances in large-scale techniques, like genomics, epigenomics, transcriptomics, and tumor immunology knowledge, have uncovered multiple genetic vulnerabilities and molecular mechanisms that drive TNBC progression and resistance to therapy. In parallel, emerging precision oncology strategies include immune checkpoint inhibitors and novel targeted agents, which have shown promising results in some patients, supporting the importance of personalized approaches in TNBC treatment. This Topic aims to compile original research, comprehensive reviews, and case studies focused on the biological mechanisms and clinical management strategies of TNBC. The scope includes the following: Genetic and epigenetic alterations in TNBC Identification and validation of novel biomarkers; Multi-omics integration and subtype classification; Mechanisms of therapeutic resistance; Immune microenvironment and immunotherapy; Novel drug targets and preclinical models; Population-based studies and Disparities in TNBC outcomes. We welcome multidisciplinary contributions from molecular biology, bioinformatics, pharmacology, oncology, pathology, and public health to foster collaboration and innovation in tackling TNBC's unique challenges.

Dr. Tatiana de Almeida Simão
Dr. Sheila Coelho Soares-Lima
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Cancers cancers	4.4	8.8	2009	20.3 Days	CHF 2900	Submit
Diagnostics diagnostics	3.3	5.9	2011	21 Days	CHF 2600	Submit
Journal of Clinical Medicine jcm	2.9	5.2	2012	17.7 Days	CHF 2600	Submit
Life life	3.4	6.0	2011	19.3 Days	CHF 2600	Submit
Medical Sciences medsci	4.4	8.7	2013	24.3 Days	CHF 1600	Submit
Current Oncology curroncol	3.4	4.9	1994	21.5 Days	CHF 2200	Submit

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All Cancers Diagnostics JCM Life Medical Sciences Current Oncology

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16 pages, 521 KB  

Open AccessArticle

Triple-Negative Apocrine Carcinoma: Largest Cohort Highlights Unique Biology and Survival Advantage

by Tugba Basoglu, Ugur Ozkerim, Sila Oksuz, Oguzcan Kinikoglu, Sedat Yildirim, Sermin Kokten, Heves Surmeli, Deniz Isik, Ozlem Nuray Sever, Seval Ay Ersoy, Hatice Odabas and Nedim Turan

J. Clin. Med. 2025, 14(19), 7103; https://doi.org/10.3390/jcm14197103 - 9 Oct 2025

Viewed by 104

Abstract

Background/Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous entity lacking ER, PR, and HER2, with aggressive biology and high recurrence risk. Neoadjuvant chemotherapy (NACT) is the standard of care, and a pathological complete response (pCR) is a surrogate marker for survival. Within [...] Read more.

Background/Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous entity lacking ER, PR, and HER2, with aggressive biology and high recurrence risk. Neoadjuvant chemotherapy (NACT) is the standard of care, and a pathological complete response (pCR) is a surrogate marker for survival. Within TNBC, apocrine differentiation (TNAC) is a distinct subtype, often androgen receptor (AR)-positive, with lower chemosensitivity but a favorable prognosis. Comparative studies of TNAC versus classical TNBC remain limited. This study aimed to define clinical and biological differences between TNAC and non-apocrine TNBC (NA-TNBC), representing the largest TNAC cohort to date. Methods: This retrospective study included 129 non-metastatic TNBC patients treated with NACT and surgery (2010–2020). Patients were classified as TNAC or NA-TNBC. Demographic, clinicopathological, and immunohistochemical data (including Ki-67 and AR) were collected. Tumor-infiltrating lymphocytes (TILs), delta Ki-67, pathological complete response (pCR), and survival outcomes were evaluated. Results: Of 129 TNBC patients, 45 (34.9%) were TNAC. AR positivity occurred in 64.4% of TNACs. TNAC patients were predominantly postmenopausal. pCR rates were significantly lower in TNAC (6.6% vs. 30.9%, p = 0.002). TNACs exhibited lower baseline Ki-67, delta Ki-67, and TIL positivity (13.3% vs. 30%). Despite this, 5-year overall survival was higher in TNAC (86% vs. 78%). Delta Ki-67 > 20% strongly predicted pCR across the cohort (p < 0.001). Carboplatin was rarely used in TNAC (8.3%), but was associated with a higher pCR rate (50% vs. 2.4%, p = 0.018). Conclusions: TNAC represents a biologically distinct TNBC subtype, characterized by low pCR but favorable survival. Recognition of its unique features may guide treatment de-escalation and exploration of AR-targeted therapies. Prospective studies focusing on TNAC are warranted. Full article

(This article belongs to the Topic Triple-Negative Breast Cancer: Genetic Vulnerabilities and Emerging Targets for Precision Oncology)

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