Triple negative breast cancer (TNBC) is a type of breast cancer that lacks estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) receptors.

This means that it does not respond to hormonal therapy or HER2-targeted drugs, making it difficult to treat. TNBC is more likely to occur in younger women, African American women, and women with a BRCA1 gene mutation. However, recent advances in treatment options have shown promising results for TNBC patients.

Immunotherapy

Immunotherapy is a type of cancer treatment that uses the body’s own immune system to fight cancer cells. This approach has shown promising results for TNBC patients.

In March 2019, the FDA approved the use of immunotherapy drug atezolizumab in combination with chemotherapy for the treatment of TNBC. Atezolizumab works by blocking a protein called PD-L1, which can help cancer cells avoid detection by the immune system. By blocking PD-L1, atezolizumab allows the immune system to recognize and attack cancer cells.

Studies have shown that the combination of atezolizumab and chemotherapy can extend the progression-free survival of TNBC patients compared to chemotherapy alone.

PARP inhibitors

Poly ADP-ribose polymerase (PARP) inhibitors are a type of targeted therapy that can selectively kill cancer cells with genetic mutations, such as the BRCA mutations that are found in some TNBC patients.

PARP inhibitors work by blocking an enzyme called PARP, which helps repair DNA damage. Cancer cells with genetic mutations that impair DNA repair are more dependent on PARP to repair DNA damage, so they are more sensitive to PARP inhibitors.

In November 2018, the FDA approved the use of PARP inhibitor talazoparib for the treatment of HER2-negative, locally advanced or metastatic breast cancer with a germline BRCA1/2 mutation, including TNBC.

P13K inhibitors

The P13K pathway is a signaling pathway that is often activated in cancer cells, including TNBC cells. P13K inhibitors are a type of targeted therapy that can block this pathway.

In March 2019, the FDA approved the use of P13K inhibitor taselisib in combination with fulvestrant for the treatment of HER2-negative, hormone receptor-positive breast cancer with a PIK3CA mutation, which is present in about 30% of TNBC cases. Taselisib works by blocking the P13K pathway, which can slow or stop the growth of cancer cells.

Targeting cancer stem cells

Cancer stem cells are a small population of cells within a tumor that have stem cell-like properties. These cells are thought to be responsible for driving tumor growth and resistance to chemotherapy.

Targeting cancer stem cells is a promising approach for the treatment of TNBC. In December 2020, researchers reported that they had developed a new drug that can selectively kill cancer stem cells in TNBC. The drug, called HXR9, works by targeting a protein called HMGA2, which is important for the survival of cancer stem cells.

Preclinical studies have shown that HXR9 can kill cancer stem cells in TNBC cell lines and patient-derived xenograft models, with no toxicity to normal cells. Clinical trials are planned to test HXR9 in TNBC patients.

Combination therapies

Combination therapies that target multiple pathways involved in the growth and progression of TNBC may be more effective than single-target therapies.

In July 2020, researchers reported positive results from a clinical trial of a combination therapy for TNBC. The therapy consisted of a PARP inhibitor, a P13K inhibitor, and an immunotherapy drug called durvalumab. The trial included 54 patients with advanced TNBC who had received prior chemotherapy.

The overall response rate was 77.8%, and the disease control rate was 96.3%. The combination therapy was well tolerated, with no new safety concerns identified. These results suggest that combination therapies may be a promising approach for the treatment of TNBC.

T-cell therapy

T-cell therapy is a type of immunotherapy that involves modifying a patient’s T cells to recognize and attack cancer cells. In August 2020, researchers reported that they had developed a new T-cell therapy for TNBC.

The therapy involves genetically engineering T cells to express a chimeric antigen receptor (CAR) that targets the protein mesothelin, which is overexpressed in TNBC. Preclinical studies have shown that the CAR T cells can specifically kill TNBC cells both in vitro and in vivo. The researchers are planning to initiate a phase 1 clinical trial of this therapy in TNBC patients.

Conclusion

The treatment landscape for TNBC is rapidly evolving, with several innovative therapies showing promising results in clinical trials.

Immunotherapy, PARP inhibitors, P13K inhibitors, targeting cancer stem cells, combination therapies, and T-cell therapy are among the approaches being investigated for TNBC. These advances offer hope for TNBC patients who have limited treatment options.