HER2 is a member of the type I tyrosine kinase growth factor receptor family and participates in normal growth control mechanisms. It is overexpressed or amplified in 20% to 30% of breast cancers, as well as other carcinomas. HER2 overexpression is associated with adverse prognostic indicators in primary breast cancer, and a number of reports have shown that HER2-overexpressing breast cancer is linked to an increased rate of recurrence/metastases, and therefore, decreased disease-free and overall survival rates.
These data suggest that HER2 is an important prognostic indicator in primary and metastatic breast cancer. In addition, HER2 is associated in some (but not all) retrospective analysis with decreased sensitivity to tamoxifen(Drug information on tamoxifen) (Nolvadex) and CMF (cyclophosphamide [Cytoxan, Neosar]/methotrexate/fluorouracil), and conversely, with an apparent increased sensitivity to anthracycline-containing regimens. There is controversy about HER2 expression and resistance or sensitivity to taxanes.
Payne et al (abstract #280) report that HER2 overexpression (as determined by immunohistochemistry) was not associated with an increased rate of complete remissions in patients with locally advanced breast cancer treated with docetaxel(Drug information on docetaxel) (Taxotere). Conversely, complete remission rate was correlated with estrogen-receptor negativity.
Previous reports have shown that estrogen-receptor negativity on the one hand, and poorly differentiated tumors on the other, responded more frequently to chemotherapy, usually an anthracycline-containing regimen. Since HER2 overexpression is usually associated with estrogen-receptor negativity and is more frequent in poorly differentiated tumors, a correlation of complete remission and HER2 positivity would have been expected.
Gabriel N. Hortobagyi, MD, FACP