Understanding Triple-Negative Breast Cancer: Challenges & Innovations

Triple-Negative Breast Cancer (TNBC) remains a challenging and aggressive histological subtype of breast cancer, associated with a poorer prognosis across all stages. The finite treatment options and rapid development of treatment resistance make its management cumbersome.

TNBC accounts for 15-20 per cent of all diagnosed breast cancers. Despite its heterogeneity, TNBC lacks targeted treatments that offer both good tolerability and efficacy. Chemotherapy remains the primary treatment option, regardless of the stage of cancer. Heredity is a common factor in TNBC, as it often affects younger women with BRCA1 mutations.

Understanding Triple-Negative Breast Cancer

Triple-negative breast cancer, as the name suggests, is a type of breast cancer in which the three receptors—PR (progesterone receptor), ER (estrogen receptor), and HER2 (human epidermal growth factor receptor 2)—are negative.

To detect triple-negative breast cancer, a biopsy is performed where breast tissue is removed and sent to a lab to check for the presence of cancer cells. There are different types of biopsies; some require an incision (surgical biopsy), while others use hollow needles (core needle biopsy and fine needle aspiration). Doctors recommend biopsies based on factors such as clinical suspicion and imaging findings.

Challenges in Triple-Negative Breast Cancer

Proper diagnosis is essential for determining treatment decisions and patient prognosis. However, challenges remain in decoding tumour heterogeneity, identifying druggable biomarkers, and managing the more aggressive behaviour of TNBC compared to other subtypes. 

The targeted therapies used to treat other forms of breast cancer are ineffective against TNBC, which makes chemotherapy the cornerstone of TNBC therapy. TNBC also has the potential to recur even after successful initial treatment, making it difficult to predict its natural history. Clinicians, pharmaceutical companies, and researchers must collaborate to develop novel treatments and address these limitations.

Innovations in Triple-Negative Breast Cancer

Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy helps reduce the extent of surgery, eliminates micrometastases in the bloodstream, and offers enhanced prognosis of TNBC. It is the standard treatment for locally advanced TNBC. 

The pathological complete response rates for neoadjuvant chemotherapy in TNBC range from 50-60 per cent. The treatment includes combination chemotherapy, consisting of paclitaxel, adriamycin, and cyclophosphamide.

Immunotherapy

Recent approaches to the treatment of TNBC have emphasised the role of immunotherapy. Research on immune checkpoint inhibitors (ICIs) has helped to design individualized immunotherapy plans and select molecular subtypes that are more likely to respond to them. ICIs stimulate the immune system, including the activation of T-cells, and have become a feasible treatment alternative for TNBC.

Targeted Therapy

Unlike chemotherapy, which also harms healthy cells, targeted therapy is less damaging to normal cells. Potential therapies for TNBC have emerged by investigating multiple categories of inhibitors.

PARP inhibitors such as talazoparib, rucaparib, olaparib, and niraparib have been FDA-approved for cancer treatment. Among these, talazoparib and olaparib are approved for treating BRCA-mutated metastatic breast cancer. Trop-2 inhibitors, like sacituzumab govitecan, have been added to the treatment armamentarium for TNBC.

Anti-androgen therapy is another promising option for TNBC. Clinical results show that enzalutamide offers clinical benefits for androgen receptor-positive (AR+) TNBC, and lower toxicity levels of this therapy make it a useful option for TNBC patients.

The challenges surrounding the treatment of triple-negative breast cancer persist due to limited therapeutic options and poor prognosis. However, efforts and research are underway to strengthen the immune response in TNBC patients by exploring rational combination approaches and uncovering mechanisms of tumor immune evasion.  Understanding the biology and complexities of TNBC can help create effective therapeutic approaches that can benefit patients through novel clinical trials.

Dr. Sai Vivek V

Guest Author Consultant - Medical Oncology and Haemato - Oncology