Predicting therapeutic response Overexpression of HER-2/neu in Breast cancer patients is associated with poor prognosis and increases disease recurrence. Overexpression HER-2/neu also predicts good response to herceptin but is not a good predictor of response to chemotherapy and overall survival. Because of its prognostic role as well as its ability to predict response to Herceptin (transtuzumab) breast cancers are routinely checked for overexpression of HER-2/neu. HER-2/neu erh-B, stands for Human e i idermal * rowth factor rece i tor. It is a molecule present in small amounts on the surface of ceain types of cells such as breast cells and ovarian cells. HER-2 belongs to Erb protein family commonly known as epidermal growth factor receptor family (EGFR). - The epidermal growth factor receptor are present on the cell surface and are involved in the signal transduction pathways leading to cell growth and differentiation. Activation of epidermal growth receptor (EGFR) Ligand binds to the EGFR Dimerisation of EGFR Activation of EGFR vir Signal transduction to nucleus 'Jr Cell growth and differentiation Although HER-2 is highly hontologus to EGFR, it does not have any specific ligand for it. Therefore it is also called orphan receptor. - Instead of activation by direct ligand binding it exhibits "constitutive activity" in the absence of ligand. The constitutive activity of the HER-2 is increased by overexpression of HER-2. - The most common mechanism by which HER-2 gets activated and transforms cells is by overexpression of normal HER-2. This phenomenon is observed in breast cancers. There are ceain types of breast cancers that overexpress HER-2/neu receptors on their surfaces. - In 1 out of every 5 breast cancers the cancer cells make an excess of HER-2/neu. - HER-2 positive breast cancers tend to be more aggressive than other types of breast cancer. - Overexpression of this receptor in breast cancer is associated with increased disease recurrence and worse prognosis. - They are also less responsive to hormone treatment However drugs that specifically target HER-2 are very effective. -Herceptin (Transtuzumb) is a drug that specifically targets HER-2 receptors and blocks their action. - Herceptin or transtuzumab is approved for HER-2/neu overexpressing breast cancer. Because of its prognostic role as well as it ability to predict response to Herceptin (transtuzumab) breast cancers are routinely checked for overexpression of HER2Inett.