HER2 positive

HER2 Positive

HER2 positive refers to a subtype of breast cancer characterized by the overexpression of the human epidermal growth factor receptor 2 (HER2) protein. This condition is significant in the context of breast cancer as it influences both the prognosis and the treatment strategies employed.

Overview

HER2, also known as ERBB2, is a gene that encodes a transmembrane receptor protein involved in the regulation of cell growth and differentiation. In approximately 15-20% of breast cancer cases, the HER2 gene is amplified, leading to an overproduction of the HER2 protein on the surface of cancer cells. This overexpression is associated with more aggressive tumor behavior and a poorer prognosis compared to HER2-negative breast cancers.

Pathophysiology

The HER2 protein is a member of the epidermal growth factor receptor (EGFR) family, which plays a critical role in the signaling pathways that control cell division and survival. In HER2 positive breast cancer, the overexpression of HER2 leads to increased signaling through the PI3K/AKT and MAPK pathways, promoting cell proliferation and inhibiting apoptosis. This results in more aggressive tumor growth and a higher likelihood of metastasis.

Diagnosis

The diagnosis of HER2 positive breast cancer is typically made using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests.

• Immunohistochemistry (IHC): This test measures the amount of HER2 protein on the surface of cells in a breast cancer tissue sample. The results are scored on a scale from 0 to 3+, with 3+ indicating HER2 positivity.

• Fluorescence In Situ Hybridization (FISH): This test detects the number of copies of the HER2 gene in cancer cells. A positive FISH test indicates HER2 gene amplification.

Treatment

The treatment of HER2 positive breast cancer has been revolutionized by the development of targeted therapies. These therapies specifically target the HER2 protein and have significantly improved outcomes for patients.

• Trastuzumab (Herceptin): A monoclonal antibody that binds to the HER2 protein, inhibiting its activity and marking the cancer cells for destruction by the immune system.

• Pertuzumab (Perjeta): Another monoclonal antibody that prevents HER2 from dimerizing with other HER family receptors, further inhibiting signaling pathways.

• Ado-trastuzumab emtansine (Kadcyla): An antibody-drug conjugate that delivers cytotoxic agents directly to HER2 positive cancer cells.

• Lapatinib (Tykerb): A small molecule tyrosine kinase inhibitor that blocks the HER2 and EGFR pathways.

Prognosis

The prognosis for patients with HER2 positive breast cancer has improved significantly with the advent of targeted therapies. While historically associated with a poorer outcome, the use of HER2-targeted treatments has led to better survival rates and reduced recurrence.

Also see

• Breast Cancer
• Targeted Therapy
• Monoclonal Antibody
• Epidermal Growth Factor Receptor