Pathophysiology
Clinical meaning
Breast cancer arises from the malignant transformation of mammary epithelial cells through the accumulation of genetic and epigenetic alterations affecting oncogenes and tumor suppressor genes. Understanding molecular subtypes is essential for advanced prescriptive management and screening risk stratification. Molecular subtypes are classified by gene expression profiling into four clinically actionable categories. Luminal A (ER+/PR+/HER2-/low Ki-67) is the most common (40-50%), driven by estrogen receptor alpha (ERα) transcriptional activation of cell proliferation genes. These tumors have the best prognosis and respond to endocrine therapy. Luminal B (ER+/PR+/-/HER2+/-/high Ki-67) has higher proliferative index and poorer prognosis than Luminal A. HER2-enriched (ER-/PR-/HER2+) tumors overexpress human epidermal growth factor receptor 2 (HER2/ERBB2) through gene amplification on chromosome 17q12, causing constitutive activation of the RAS-MAPK and PI3K/AKT proliferation cascades. Triple-negative breast cancer (TNBC - ER-/PR-/HER2-) lacks all three receptors, is highly proliferative, and disproportionately affects BRCA1 mutation carriers and young African American women. Hereditary breast cancer accounts for 5-10% of all breast cancers. BRCA1 (chromosome 17q21) and BRCA2 (chromosome 13q12.3) are tumor suppressor genes encoding proteins essential for homologous recombination repair (HRR) of double-strand DNA...