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Updated: May 20, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy
Suryakant Niture1, Subhajit Ghosh1, Jerry Jaboin1
1Department of Radiation Oncology, Stephenson Cancer Center, Oklahoma University, Oklahoma City, OK 73104, USA.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and HER2 expression. While TNBC is relatively less common, accounting for only 10-15% of initial breast cancer diagnosis, due to its aggressive nature, it carries a worse prognosis in comparison to its hormone receptor-positive counterparts. Despite significant advancements in the screening, diagnosis, and treatment of breast cancer, TNBC remains an important public health burden. Following treatment with chemotherapy, surgery, and radiation, over 40% of TNBC patients experience relapse within 3 years and achieve the least benefit from post-mastectomy radiation. The tumor microenvironment environment (TME) is pivotal in TNBC initiation, progression, immune evasion, treatment resistance, and tumor prognosis. TME is a complex network that consists of immune cells, non-immune cells, and soluble factors located in the region adjacent to the tumor that modulates the therapeutic response differentially between hormone receptor-positive breast cancer and TNBC. While the mechanisms underlying the radiation resistance of TNBC remain unclear, the immunosuppressive TME of TNBC has been implicated in chemotherapeutic resistance. Radiation therapy (RT) is known to alter the TME; however, immune changes elicited by radiation are poorly characterized to date, and whether these immune changes contribute to radiation resistance remains unknown. This review delves into the distinct characteristics of the TNBC TME, explores how RT influences TME dynamics, and examines mechanisms underlying tumor radiosensitization, radioresistance, and immune responses.
Insights
Triple-negative breast cancer (TNBC) is aggressive and resistant to treatment. Understanding its tumor microenvironment (TME) and radiation therapy
Area of Science:
- Oncology
- Immunology
- Radiotherapy Research
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 receptors, posing significant treatment challenges and a worse prognosis.
- Despite advances, TNBC patients face high relapse rates and limited benefit from standard therapies, including radiation therapy (RT).
- The tumor microenvironment (TME) plays a critical role in TNBC progression, immune evasion, and treatment resistance, but its specific influence on radiation resistance is unclear.
Purpose of the Study:
- To review the distinct characteristics of the TNBC tumor microenvironment (TME).
- To explore how radiation therapy (RT) influences TME dynamics in TNBC.
- To examine the mechanisms of tumor radiosensitization, radioresistance, and immune responses within the TNBC TME following RT.
Main Methods:
- Literature review focusing on TNBC, tumor microenvironment (TME), radiation therapy (RT), and immune responses.
- Analysis of existing research on the interplay between RT, TME components, and therapeutic outcomes in TNBC.
- Synthesis of data to elucidate mechanisms of radiation resistance and radiosensitization.
Main Results:
- The immunosuppressive TME of TNBC is implicated in resistance to chemotherapy and potentially radiation therapy.
- Radiation therapy (RT) is known to alter the TME, but the resulting immune changes and their contribution to radiation resistance are poorly understood.
- Distinct TME characteristics in TNBC influence its response to RT differently compared to other breast cancer subtypes.
Conclusions:
- The tumor microenvironment (TME) is a key determinant of triple-negative breast cancer (TNBC) response to radiation therapy (RT).
- Further research is needed to characterize RT-induced immune changes in the TME and their role in TNBC radiosensitivity and radioresistance.
- Understanding TME dynamics is crucial for developing novel therapeutic strategies to overcome RT resistance in TNBC.
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