Adjuvant Trastuzumab in HER2-Positive Breast Cancer

Trastuzumab added to a nonanthracycline regimen to treat HER2-positive breast cancer resulted in rates of disease-free and overall survival that were similar to those for an anthracycline-containing regimen, with lower rates of cardiac toxicity and secondary leukemia. The HER2 gene encodes a tyrosine kinase receptor that mediates critical signaling functions in normal and malignant breast epithelial cells. 1 An acquired alteration consisting of amplification and overexpression of the gene product occurs in approximately 20 to 25% of human breast cancers. 2 , 3 HER2 overexpression is associated with an aggressive clinical phenotype that includes high-grade tumors, increased growth rates, early systemic metastasis, and decreased rates of disease-free and overall survival. 2 , 3 Preclinical data indicate that this adverse clinical picture results from fundamental changes in the biologic features of breast-cancer cells containing the alteration, including increased proliferation, suppression of apoptosis, increased . . .