Breast cancer is the most common form of cancer in women in the United States. In 2010, approximately 207,000 women were diagnosed with breast cancer and nearly 40,000 died of the disease. Survival from breast cancer is related to the extent of disease at diagnosis; 98.6% of women diagnosed with localized disease (60% of cases) are living 5 years after diagnosis, while women who present with metastatic disease (5% of cases) have a much lower 5-year survival rate of 23.4%. Breast cancer does occur in men but is much less common than in women. Most breast
cancers are epithelial in origin, developing from the breast ducts or lobules. Established prognostic factors for breast cancer include tumor stage, lymph node involvement, patient age at diagnosis, tumor size and grade, estrogen (ER) and progesterone receptor (PR) status, and genetic factors,
including human epidermal growth factor receptor 2 (HER2), and inheritance of a breast cancer susceptibility gene variant (i.e., BRCA1 or BRCA2). Treatment for breast cancer includes surgical removal of localized tumor preceded or followed by chemotherapy or radiation therapy to eradicate
residual tumor and prevent recurrence. Anthracyclines are antibiotic chemotherapeutic agents used widely in breast cancer treatment. Anthracyclines are effective in many, but not all, breast cancer patients, and are associated with long-term cardiac risks, including cardiomyopathy and congestive
heart failure, and the development of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Due to their toxicity and variable effectiveness, biomarkers predictive of response to anthracycline therapy have been sought. Current evidence points to the HER2 gene as a potential biomarker, but studies are not conclusive and the mechanism by which HER2-positive tumors may be susceptible to anthracycline therapy is not understood. It has been proposed by some researchers that HER2 is a surrogate biomarker of anthracycline therapy response, and that TOP2A, another gene located in close proximity to HER2 on chromosome 17, is in fact the relevant biomarker for prediction of response to anthracycline therapy. TOP2A encodes topoisomerase II alpha, a molecular target of anthracyclines; therefore, TOP2A alteration may provide a biological explanation for differential response to anthracycline therapy.