Understanding the Challenges of TNBC and HER2 Breast Cancer

TNBC, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and low levels of HER2 protein, accounts for approximately 15% of breast cancer cases. This subtype is known for its aggressive nature, high recurrence rates, and limited treatment options, as it lacks targeted therapies found in hormone receptor-positive breast cancers. On the other hand, HER2-positive breast cancer is driven by the overexpression of the HER2 protein, which can be targeted by therapies such as trastuzumab (Herceptin). Despite the effectiveness of these treatments, a significant portion of patients still experience treatment resistance and disease relapse.

Identifying Prognostic Biomarkers for Breast Cancer Survival

The identification of reliable prognostic biomarkers is critical for improving survival outcomes among TNBC and HER2-positive patients. A recent study revealed that certain gene expression patterns, including those related to immune response and neuronal function, could predict recurrence risk (Zhanrong Zhang et al., 2025).

By analyzing RNA sequencing data from 155 TNBC patients, researchers developed a prognostic model that effectively predicts long-term survival based on gene signatures associated with early recurrence. This multifaceted approach underscores the potential to personalize treatment and monitor patient responses more effectively.

Role of ZNF469 in Regulating Collagen and Liver Fibrosis

A significant discovery in the realm of breast cancer treatment is the role of the transcription factor ZNF469 in regulating collagen production, which is particularly relevant in the context of liver fibrosis (Steinhauser et al., 2025). ZNF469 has been identified as a crucial player in the fibrogenic response, demonstrating a regulatory function in collagen gene expression in hepatic stellate cells (HSCs).

This finding is particularly relevant for breast cancer patients with liver metastases, where fibrosis can complicate treatment and negatively impact prognosis. Understanding the mechanisms through which ZNF469 influences fibrosis may open new avenues for therapeutic interventions aimed at mitigating fibrotic responses in patients undergoing treatment for metastatic breast cancer.

Impact of CAR-T Cell Therapy on Tumor Response and CRS

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment modality for various cancers, including breast cancer. However, the effectiveness of CAR-T therapy is often marred by the occurrence of cytokine release syndrome (CRS) and disease relapse.

A recent mathematical model explored the dynamics of CAR-T cell therapy, elucidating how macrophage activation contributes to CRS and influences treatment outcomes (Santurio et al., 2025). The model demonstrated that specific pathways, including the CD40-CD40L interaction, are significant drivers of cytokine release. This knowledge enables clinicians to devise strategies that mitigate CRS while enhancing the therapeutic efficacy of CAR-T cell therapy.

Enhancing Treatment Outcomes through Personalized Approaches

Given the heterogeneity of breast cancer, personalized treatment approaches are becoming increasingly important. By integrating genomic profiling, clinicians can tailor therapies based on individual tumor characteristics, improving response rates and minimizing adverse effects.

The use of machine learning algorithms in predicting treatment responses has shown promise, enabling the identification of patients who may benefit from specific therapies based on their tumor’s molecular profile. For instance, a prognostic model utilizing gene expression data has been validated in predicting survival outcomes for both TNBC and HER2-positive patients, underscoring the importance of personalized medicine in breast cancer treatment.

Conclusion

The landscape of breast cancer treatment is evolving rapidly, with significant advancements in our understanding of TNBC and HER2-positive subtypes. By focusing on the identification of prognostic biomarkers, the role of key regulatory proteins, and the integration of novel therapies like CAR-T, the potential to improve survival outcomes for breast cancer patients is greater than ever.

References

1. Zhanrong, Z., Zhengbo, T., & Zheng, Z. (2025). Single-cell transcriptomic analysis reveals AP-1 downregulation remodels bone marrow environment and contributes to osteopenia in ovariectomized mice. Journal of Orthopaedic Translation. https://doi.org/10.1016/j.jot.2025.03.001

2. Steinhauser, S., Estoppey, D., & Buehler, D. P. (2025). The transcription factor ZNF469 regulates collagen production in liver fibrosis. JCI Insight. https://doi.org/10.1172/jci.insight.182232

3. Santurio, D. S., Barros, L. R. C., & Glauche, I. (2025). Mathematical modeling unveils the timeline of CAR-T cell therapy and macrophage-mediated cytokine release syndrome. PLoS Computational Biology. https://doi.org/10.1371/journal.pcbi.1012908

4. Eckel, O., Mirea, M. A., & Gschwendtner, A. (2025). Expression of the cholesterol transporter SR-B1 in melanoma cells facilitates inflammatory signaling leading to reduced cholesterol synthesis. Neoplasia. https://doi.org/10.1016/j.neo.2025.101154

5. Khan, H., Javaid, S., & Ashraf, W. (2025). Erqember mitigates neurotoxic effects of aluminum chloride in mice: Phytochemical insights with neurobehavioral and in silico approaches. Journal of Toxicology

FAQ

What are the key challenges in treating TNBC and HER2-positive breast cancer?

The primary challenges include the aggressive nature of TNBC, the lack of specific targets for therapy, and the tendency of HER2-positive cancers to develop resistance to treatments.

How can prognostic biomarkers improve breast cancer treatment?

Prognostic biomarkers can help identify patients at risk of recurrence, enabling personalized treatment plans that improve outcomes and minimize unnecessary side effects.

What is the role of ZNF469 in breast cancer?

ZNF469 has been identified as a regulator of collagen production in liver fibrosis, which is relevant for patients with metastatic breast cancer, potentially influencing treatment responses.

How does CAR-T cell therapy work in breast cancer?

CAR-T cell therapy harnesses the patient’s immune cells to target and kill cancer cells, but it can lead to side effects such as cytokine release syndrome, which complicates treatment.

Why is personalized medicine important in breast cancer?

Personalized medicine allows for tailored treatment strategies based on individual tumor characteristics, improving efficacy and reducing the risk of adverse effects for patients.