A 48-year-old woman with invasive breast cancer has tumor cells showing 3+ staining for HER2/neu on immunohistochemistry. HER2 (ERBB2) is a member of the epidermal growth factor receptor family. The oncogenic mechanism in HER2-amplified breast cancer is:

• A A constitutively active GTPase that cannot hydrolyze GTP
• B A fusion protein with tyrosine kinase activity
• C Ligand-independent dimerization and signaling of a receptor tyrosine kinase ✓
• D Loss of a DNA mismatch repair protein

Explanation

HER2 amplification causes overexpression of the receptor, leading to ligand-independent homodimerization and heterodimerization, resulting in constitutive downstream proliferative signaling. Trastuzumab targets HER2. Option A describes oncogenic RAS mutations. Option B describes BCR-ABL. Option D describes Lynch syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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