1 Patients with breast cancer are treated with a combination of therapies to include surgery, chemotherapy, endocrine therapy, targeted monoclonal antibody (mAb) therapy and radiation as dictated by characteristics of their tumor and disease stage. 2 Patients with hormone receptor (HR) positive tumors are routinely administered endocrine therapy and patients with HER2-positive tumors receive trastuzumab, a humanized mAb targeting HER2, as a component of their standard of care therapy. Despite advances in treatment, approximately 10% of women with breast cancer will recur and succumb to their disease by the five-year mark; a number that increases to 17% at ten years. 1 1.2 HER2-positive breast cancer HER2 is a member of the epidermal growth factor receptor family of receptor tyrosine kinases. It is expressed in approximately 70-80% of invasive breast cancers and amplified and/or overexpressed (= HER2-positive) in approximately 20%. 3,4 HER2-positive breast cancers are more aggressive and susceptible to recurrence than HER2-normal cancers. HER2 is routinely assessed on breast tumors using immunohistochemistry (IHC) to detect protein expression or in situ hybridization (ISH) to identify gene amplification. IHC results are scored as 0, 1+, 2+ or 3+. ISH reports a ratio of the number of HER2 gene copies to chromosome 17 copies. According to the 2013 update of the American Society of Clinical Oncology (ASCO) and College of American Pathologist (CAP) guidelines, a tumor is considered HER2-positive if any of the following criteria are met: 5 • IHC 3+ • Dual-probe ISH ratio (HER2/CEP17) > 2.0 with HER2 copy number of >4.0/cell • Dual-probe ISH ratio (HER2/CEP17) > 2.0 with HER2 copy number of <4.0/cell • < 2.0 overall ratio with HER2 copy number of > 6.0/cell • Single probe tests average HER2 copy number of > 6.0/cell Patients with HER2-positive tumors are treated with trastuzumab, a mAb that targets the extracellular portion of the HER2 protein. Trastuzumab was first evaluated in the metastatic setting where it was shown to provide significant clinical benefit as monotherapy and in combination with chemotherapy as first- or 5 Protocol: 2014-0443 Version 2.1 Version Date: 11 April 2016 second-line therapy.