From:  Triple-negative breast cancer: current understanding and future perspectives

 Classification of breast cancer by molecular gene expression profiles.

SubtypeReceptor status/Defining featuresPrognosis and key characteristics
Luminal A [2, 10, 11]ER+/PR+/HER2–, HR+/HER2–. Characterized by low Ki-67 proliferation marker and generally low grade.Most common subtype (up to 68% of all cases). Associated with a favorable prognosis.
Luminal B [2, 10, 11]ER+, PR+/–, HER2–/+. Characterized by HR+/HER2+ and/or high Ki-67 expression. Approximately 10–30% of cases.Poorer prognosis compared to luminal A. Exhibits aggressive behavior. Higher histological grade.
HER2-enriched (HER2+) [2, 4, 10, 11]ER–/PR–/HER2+. Defined by HER2 overexpression or ERBB2 gene amplification. Constitutes 12–20% of cases.High Ki-67 expression, indicating aggressive behavior.
TNBC (basal-like) [1, 4, 7, 13]ER–/PR–/HER2–. Lacks expression of all three receptors/markers. Overlaps significantly with the basal-like molecular subtype (about 80% of TNBC cases).Most aggressive subtype. High histological grade. Associated with higher recurrence, high metastatic potential, and dismal prognosis/poor overall survival.
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This classification is crucial because the different subtypes have distinct oncogenic drivers, leading to significant variations in clinical outcomes, tumor heterogeneity, and responsiveness to specific therapeutic interventions. The molecular heterogeneity within TNBC is further elucidated by subtyping systems (e.g., Lehmann, Burstein), which identify specific targetable pathways (e.g., luminal androgen receptor (LAR), immunomodulatory (IM), mesenchymal (M), and basal-like [BL1/BL2]) to guide precision medicine efforts [4, 11, 14, 15]. ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2; ERBB2: Erb-B2 receptor tyrosine kinase 2 (also known as HER2); TNBC: triple-negative breast cancer.