Breast Cancer

Posted by Graham McMahon • October 5th, 2011

In a study from Slamon et al., 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.

Clinical Pearls

How frequently are breast cancers HER2-positive?

An acquired alteration consisting of amplification and overexpression of the gene product occurs in approximately 20 to 25% of human breast cancers.

How does the presence of HER2 overexpression affect outcome in women with breast cancer?

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.

Figure 1 Disease-free Survival among All Patients and According to TOP2A Status.

Morning Report Questions

Q: According to the results of this study, how did adding trastuzumab affect outcome among women with HER2-positive breast cancer?

A: The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over TAC plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia.

Q: What major safety issue was observed when trastuzumab was used in combination with anthracycline-based chemotherapy?

A: The major safety issue that the authors observed was increased cardiac dysfunction when trastuzumab was used in combination with anthracycline-based chemotherapy.

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