A 51-year-old woman comes to the office for a follow-up visit. Three weeks ago, she had a screening mammogram that was suspicious for malignancy. An ultrasound-guided needle aspiration was performed and showed invasive ductal carcinoma. The patient underwent a lumpectomy with axillary dissection and was found to have no metastatic disease. Immunohistochemical analysis of the tumor specimen was significant for the following: Adjuvant therapy with a monoclonal antibody is started. Which of the following is the most likely target of this drug?

Question

A 51-year-old woman comes to the office for a follow-up visit.  Three weeks ago, she had a screening mammogram that was suspicious for malignancy.  An ultrasound-guided needle aspiration was performed and showed invasive ductal carcinoma.  The patient underwent a lumpectomy with axillary dissection and was found to have no metastatic disease.  Immunohistochemical analysis of the tumor specimen was significant for the following:  Adjuvant therapy with a monoclonal antibody is started.  Which of the following is the most likely target of this drug?

Quizplus · Accepted Answer

This patient has localized invasive ductal breast carcinoma that shows estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. Trastuzumab is a monoclonal antibody used in the management of patients with HER2-positive breast cancer. It binds to a portion of the extracellular domain of HER2 and prevents activation of a transmembrane tyrosine kinase. This downregulates cellular proliferation and promotes apoptosis. Approximately 20% of all invasive breast cancers overexpress HER2; this can also be found in other solid tumors (eg, stomach, lung, ovary). (Choices A and B) Hormone receptor-positive breast cancer (ER and/or PR overexpression) is treated with antiestrogen medications to reduce tumor cell proliferation. Premenopausal patients are typically treated with selective estrogen receptor modulators (eg, tamoxifen), while aromatase inhibitors (eg, anastrozole, letrozole) are used in postmenopausal women. However, these medications are not monoclonal antibodies. (Choice C) Receptor activator of nuclear factor kappa-B ligand (RANKL) activates osteoclasts; RANKL expression on bone may contribute to bone metastases by binding to RANK on tumor cells. Denosumab, a human monoclonal antibody against RANKL, is used to reduce skeletal-related events if metastasis to bone occurs. (Choice E) Vascular endothelial growth factor (VEGF), which also binds to a tyrosine kinase receptor, induces angiogenesis. VEGF inhibitors, such as the monoclonal antibody bevacizumab, have a role in treatment of some metastatic cancers (eg, colon, lung). Educational objective: Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that is overexpressed in 20% of breast cancer patients. In such patients, HER2 blockade with the monoclonal antibody trastuzumab downregulates cellular proliferation and promotes apoptosis. __________ References: Trastuzumab--mechanism of action and use in clinical practice. (http://www.ncbi.nlm.nih.gov/pubmed/17611206) HER2: biology, detection, and clinical implications. (http://www.ncbi.nlm.nih.gov/pubmed/21204711)

A 51-Year-Old Woman Comes to the Office for a Follow-Up