THE UPFRONT THERAPY FOR HER2 POSITIVE BREAST CANCER PATIENTS

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Abstract

HER2 overexpression/amplification occurs in ∼15 to 25% of human breast cancer patients, and has traditionally been associated with a more aggressive prognosis. However, the outcome has been dramatically improved in HER2-positive metastatic breast cancer patients through the use of anti-HER2 therapy. Trastuzumab is a humanized monoclonal antibody targeted to the extracellular domain of HER2 and Lapatinib is a small-molecular tyrosine kinase inhibitor for HER1 and HER2 tyrosine autophosphorylation. Furthermore, trastuzumab improves disease-free survival and overall survival after adjuvant chemotherapy for early HER2-positive breast cancer patients. Trastuzumab is defined as the gold standard therapy for HER2-positive breast cancer patients with more than 1 cm tumor size in worldwide guideline including in Japan. One of current topics is anti-HER2 dual blockade therapy (without chemotherapy) for early HER2-positive breast cancer patients. The results for some studies from several years ago already have been reported. A new clinical trial has also been ongoing in Japan.The other topic is development of new drugs such as Pertuzumab and T-DM1. Pertuzumab is a humanized monoclonal antibody targeted to the extracellular domain-2 of HER2 and inhibits ligand-dependent HER2 dimerization and signaling. T-DM1 is a conjugate drug of trastuzumab and DM-1 (antimicrotubule drug). T-DM1 binds to HER2 with affinity similar to trastuzumab and provides intracellular delivery of DM1. Positive results using combination therapy with trastuzumab and pertuzumab were shown in HER2 positive metastatic breast cancer patients in a large phase III study (CLEOPATRA). A global phase III study (APHINITY) which includes Japan is already ongoing for early HER2 positive breast cancer patients. Furthermore, enrollment in the global phase III study (MALIANE) using T-DM1 for HER2 positive metastatic breast cancer patients has also already been completed this year. I would like to present the upfront therapy both new concepts and clinical trial data pertaining to these new drugs for HER2 positive breast cancer patients in this symposium.

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