Triple-negative breast cancer (TNBC) represents a distinct and aggressive subtype of breast cancer. Its identification is crucial for guiding effective patient care due to its unique biological characteristics. Unlike other breast cancer types, TNBC does not express certain receptors typically targeted by conventional therapies. This difference necessitates specific diagnostic approaches and tailored treatment strategies.
Defining Triple Negative
The term “triple negative” refers to the absence or very low expression of three specific receptors on the surface of breast cancer cells: the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These receptors are proteins that can drive cancer cell growth and are often targeted by specific therapies in other breast cancer subtypes. For instance, estrogen and progesterone receptors bind to hormones that can fuel cancer growth, while HER2 is a protein involved in cell growth and repair.
The lack of these three receptors means TNBC cells do not respond to hormone therapies that block ER or PR, nor to therapies that specifically target HER2. This absence fundamentally distinguishes TNBC from hormone receptor-positive and HER2-positive breast cancers, which rely on these receptors for growth. The limited number of direct targets on TNBC cells historically made treatment more challenging compared to other breast cancer types.
Identifying the Diagnosis
Diagnosing triple-negative breast cancer involves identifying the absence of key receptors. This begins after a breast biopsy, where a small tumor tissue sample is obtained and sent to a laboratory for specialized testing.
Immunohistochemistry (IHC) is the primary method used to determine the status of ER, PR, and HER2 protein expression. IHC uses antibodies that bind to these specific proteins, allowing pathologists to visualize their presence or absence in tumor cells. If IHC results for HER2 are inconclusive, fluorescence in situ hybridization (FISH) may be performed to check for amplification of the HER2 gene. A diagnosis of triple-negative breast cancer is confirmed when the tumor tests negative for ER, PR, and HER2 through these methods.
Current Treatment Approaches
Treatment for triple-negative breast cancer primarily relies on chemotherapy due to the absence of specific receptor targets. Chemotherapy can be administered before surgery (neoadjuvant) to shrink the tumor or after surgery (adjuvant) to eliminate remaining cancer cells and reduce recurrence risk. Commonly used chemotherapy agents include taxanes and anthracyclines, which are often effective in this subtype.
Advancements have introduced targeted therapies and immunotherapies into treatment for specific cases. For individuals with BRCA-mutated tumors, PARP inhibitors like olaparib (Lynparza) and talazoparib (Talzenna) are approved. These drugs interfere with DNA repair pathways in cancer cells, specifically those with BRCA gene mutations, leading to cell death.
Immunotherapy, particularly immune checkpoint inhibitors, is a treatment option for patients whose tumors express programmed death-ligand 1 (PD-L1). Pembrolizumab (Keytruda) and atezolizumab (Tecentriq), both PD-1/PD-L1 inhibitors, are approved for use with chemotherapy for PD-L1 positive advanced TNBC. These therapies help the body’s immune system recognize and attack cancer cells by blocking proteins cancer cells use to evade immune detection. Sacituzumab govitecan (Trodelvy), an antibody-drug conjugate (ADC), is also approved for certain metastatic TNBC cases, delivering a chemotherapy drug directly to cancer cells that express the TROP2 protein.
Understanding the Outlook
Triple-negative breast cancer is considered more aggressive than other breast cancer subtypes, characterized by faster growth and a higher likelihood of spreading and recurring. Despite this aggressive nature, treatment advancements have led to improved outcomes for many patients. The prognosis can be influenced by several factors, including the stage of cancer at diagnosis and how well the tumor responds to initial treatment.
For localized TNBC that has not spread beyond the breast, the five-year relative survival rate is approximately 91%. If the cancer has spread to nearby lymph nodes or regions, the five-year survival rate is around 65%. When the cancer has spread to distant parts of the body, the five-year survival rate is lower, at about 12%. These statistics are historical averages, and ongoing treatment innovations continue to improve patient outlooks.
Future Directions in Treatment
Research into triple-negative breast cancer treatments continues to evolve, focusing on developing novel therapies. Efforts are concentrated on identifying new targets on cancer cells and exploring innovative combinations of treatments. Emerging strategies include new antibody-drug conjugates (ADCs) beyond currently approved options, which aim to deliver potent anti-cancer drugs more precisely to tumor cells.
New immunotherapy combinations are also under investigation, exploring ways to enhance the immune system’s response against TNBC cells, potentially even for tumors that do not express high levels of PD-L1. Clinical trials are actively evaluating these novel agents and combinations, including bispecific antibodies and other targeted agents. These ongoing studies offer hope for expanding the range of effective treatments and improving outcomes for individuals with triple-negative breast cancer.