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HER2-positive breast cancers constitute 25-30% of breast cancers in women. These cancers have a different natural history, clinical course, and prognosis. After the discovery of HER2 amplification, various molecules have been developed to manipulate the activity of this biomarker. In this review, an attempt has been made to understand the possible ways of managing HER2-positive breast cancers in women in an era where we have a number of monoclonal antibodies and small molecule inhibitor to manipulate the activity of HER2.