With the introduction of
anthracycline-based regimens, 5-year survival rates have significantly improved in patients with early-stage
breast cancer. With the addition of
trastuzumab, a
monoclonal antibody targeting the human
epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. Subsequently,
lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific
tyrosine kinase inhibitor, received Food and Drug Administration (FDA) approval in combination with
capecitabine for patients with advanced HER2+
breast cancer. Then,
pertuzumab in 2012 and
ado-trastuzumab emtansine in 2013 were approved in the US and elsewhere based on evidence showing an improvement in survival outcomes in patients with mostly
trastuzumab naïve or
trastuzumab-exposed metastatic disease. The FDA also approved 1 year of extended adjuvant
neratinib after
chemotherapy and a year of
trastuzumab for HER2-positive
breast cancer on the basis of the ExteNET trial. The clinical benefit demonstrated by those drugs in advanced disease has triggered several adjuvant and neoadjuvant trials testing them in combination with
chemotherapy, but also without conventional
chemotherapy, using single or dual HER2-targeting drugs. In this article, we review the current data on the therapeutic management of HER2-positive early-stage
breast cancer in the adjuvant and neoadjuvant setting. We also review the data the efficacy and safety of
anthracycline-based and nonanthracycline-based
adjuvant chemotherapy regimens combined with
trastuzumab, and optimum
chemotherapy regimens in small HER2-positive
tumors.