Adjuvant Trastuzumab in HER2-Positive Breast Cancer

In the fourth large study, the Breast Cancer International Research Group 006 trial, we evaluated adjuvant therapy with trastuzumab but included a second trastuzumab-containing regimen, which did not have an anthracycline

Dennis Slamon

2011

Scholarcy highlights

  • Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, combined therapy with anthracycline-based regimens has been associated with cardiac toxicity
  • The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group
  • An acquired alteration consisting of amplification and overexpression of the gene product occurs in approximately 20 to 25% of human breast cancers
  • HER2 overexpression is associated with an aggressive clinical pheno-type that includes high-grade tumors, increased growth rates, early systemic metastasis, and decreased rates of disease-free and overall survival
  • 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 motility, greater invasive and metastatic potential, accelerated angiogenesis, and steroid hormone independence
  • A significant difference in sustained, subclinical loss of mean left ventricular ejection fraction was observed in the group receiving AC-T plus trastuzumab, as compared with the TCH group, with a rate of 11.2% in the AC-T group
  • Detailed data derived from an analysis of the TOP2A gene in our study showed that TOP2A coamplification occurred in 35% of HER2-positive patients and was directly associated with the incremental benefit that anthracyclines provide over nonanthracycline regimens in HER2-positive disease
  • The her gene encodes a tyrosine kinase receptor that mediates critical signaling functions in normal and malignant breast epithelial cells. An acquired alteration consisting of amplification and overexpression of the gene product occurs in approximately 20 to 25% of human breast cancers. HER2 overexpression is associated with an aggressive clinical pheno-type that includes high-grade tumors, increased growth rates, early systemic metastasis, and decreased rates of disease-free and overall survival. 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 motility, greater invasive and metastatic potential, accelerated angiogenesis, and steroid hormone independence

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