Modern Immunotherapy for Triple-Negative Breast Cancer

Introducing innovative drugs to standard clinical cancer therapies, including TNBC, allows for an increase in the response rate to the applied treatment, thereby extending the lives of cancer patients.

FREMONT, CA: Patients diagnosed with breast cancer (BC) are increasing every year. Moreover, triple-negative breast cancer (TNBC) may account for 10–15 per cent of diagnosed breast cancer cases. This subtype of tumour is more common in patients under the age of 40 who have a BRCA 1 mutation. Much research is conducted to better recognise the molecular phenotypes of breast cancer, helping to adjust treatment and develop new therapeutic opportunities.

The clinical classification of BC includes hormone receptor-positive tumours with the expression of oestrogen (ER) and progesterone (PR) receptors, human epidermal receptor 2 (HER2)-enriched tumours with overexpression of HER2 in the absence of HR expression, and triple-negative tumours without the expression of these three receptors. In addition, BC is classified into molecular subtypes based on immunohistochemical markers and complementary DNA (cDNA) microarrays.

As TNBC does not express ER, PR, or HER2, it is more diverse than other types in terms of worse outcomes, narrow therapeutic possibilities, and malignant characteristics like rapid growth and the formation of metastases. Its aggressive features reflect the dismal prognosis including the median overall survival of metastatic TNBC is 8 to 15 months. Due to the actionable molecular targets, chemotherapy remains the primary option in TNBC treatment. However, systemic chemotherapy provokes adverse effects, and most patients quickly develop resistance.

Furthermore, TNBC relapses frequently, necessitating the development of new therapeutic strategies.

The immune system is an important factor in the fight against cancer. Its role is to prevent the growth of neoplasms by destroying cancer cells and decreasing the possibility of metastasizing. However, it can encourage tumour progression and is self-controlled by immune checkpoints to protect the body’s natural, healthy cells from immune-mediated death or peripheral tolerance.

The basis of this peripheral tolerance is the recognition and binding of a T-cell receptor (TCR) to an antigen presented in the primary histocompatibility complex (MHC) on the surface of an antigen-presenting cell (APC). The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and its ligands (PD-L1) are included in the suppression of the T-cell immune response. CTLA-4 and PD-1 pathways play roles at different stages of immune system activity. CTLA-4 is responsible for inhibiting a potentially autoaggressive T-cell at the early stages, particularly in the lymph nodes. While the PD-1 pathway offers self-tolerance by regulating activated T-cells at the later stages of an immune response.

Immunotherapy has shown high efficacy in the treatment of a few types of tumours, such as melanoma, kidney, and non-small cell lung cancer (NSCLC), and includes immune checkpoint inhibitors (ICIs) as indications for treatment. In TNBC with a lack of ER, PR, and HER2, the use of monoclonal antibodies or other therapeutic options like chemotherapy, radiotherapy, and selected targeted therapies is effective in the early or advanced stages of TNBC.