TNBCs

Triple-negative breast cancers (TNBCs) are breast cancers that lack expression of estrogen receptor (ER) and progesterone receptor (PR) and do not have amplification of the HER2 gene. They account for about 10–20% of breast cancers and tend to occur in younger patients, often in certain ethnic groups. Clinically, TNBCs are usually more aggressive, tend to be higher grade, and have a higher risk of early relapse and distant metastasis compared with other breast cancer subtypes.

Biology and subtypes of TNBC are heterogeneous. Many TNBC tumors are basal-like by gene expression profiling, but within TNBC there are multiple molecular subtypes with distinct patterns of growth and metastasis. BRCA1 and other DNA repair gene mutations are relatively more common in TNBC, and tumors with these defects may respond to certain targeted therapies, such as PARP inhibitors.

Treatment considerations for TNBC center on chemotherapy, as endocrine therapies and HER2-targeted therapies are not effective for these tumors. In early-stage disease, standard treatment often combines surgery, radiation, and neoadjuvant or adjuvant chemotherapy; adding immunotherapy in the neoadjuvant setting has shown improved responses in some trials. In advanced or metastatic TNBC, immune checkpoint inhibitors (for example, pembrolizumab in combination with chemotherapy for PD-L1–positive tumors) have shown benefit in selected patients. The antibody-drug conjugate sacituzumab govitecan is approved for metastatic TNBC after at least two prior therapies and has demonstrated improvements in progression-free and overall survival in the ASCENT trial. For BRCA-mutated TNBC, PARP inhibitors are available in approved indications.

Prognosis varies with stage and response to therapy; TNBC generally carries a poorer prognosis than other breast cancer subtypes, particularly if not detected early. Ongoing research aims to refine molecular subtypes, identify predictive biomarkers, and develop targeted therapies to improve outcomes.