TNBC

TNBC, or triple-negative breast cancer, is a form of breast cancer defined by lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for about 10-20% of invasive breast cancers and tends to affect younger women and those of African descent. TNBC tumors are more likely to be high grade and proliferative, with a higher risk of early recurrence and metastasis.

Biology and subtypes: The term reflects receptor status, not a single disease. Many TNBCs are basal-like by gene expression, but not all. Molecular studies identify subtypes such as basal-like 1 and 2, mesenchymal, immunomodulatory, and luminal androgen receptor. BRCA1-associated cancers are enriched in TNBC. BRCA1/2 germline mutations increase risk and may guide therapy in some settings.

Diagnosis and prognosis: Diagnosis relies on tumor receptor testing. Because there are no approved receptor targets for all TNBCs, systemic chemotherapy is the main treatment, with surgery and radiation for localized disease. Prognosis is generally poorer than for other breast cancers, especially in the first 3-5 years; achieving pathologic complete response after neoadjuvant therapy is linked with better outcomes.

Treatment landscape: Stage guides therapy. Neoadjuvant or adjuvant chemotherapy is common. In metastatic TNBC, options include chemotherapy and, in selected patients, PARP inhibitors for BRCA1/2 mutations and antibody-drug conjugates such as sacituzumab govitecan. Immunotherapy with checkpoint inhibitors has shown benefit in certain PD-L1–positive cases when combined with chemotherapy. Research continues to identify biomarkers and new targeted therapies.