The epidermal growth factor receptor family in breast cancer

The human epidermal growth factor receptor (HER) family comprises four homologous members: EGFR, HER-2, HER-3, and HER-4. The activation of these receptors triggers a complex series of signal transduction pathways which affect pivotal tumorigenic processes. The deregulation of HER signaling is seen in several human malignancies. HER-2 is now recognized as a key oncogene in breast cancer pathogenesis. Assessment of HER-2 status is of central importance in the prognosis of breast cancer patients. In the light of clinical data suggesting that HER-2 can also be useful as a predictive marker both for trastuzumab and chemotherapy, standardized determination of the HER-2 status in tumors has become more important. Moreover, current data provide evidence for the significance of HER-3 and HER-4 alterations in breast carcinogenesis. Because of the complex interactions among the HER receptors, it is likely that the effect on cell proliferation and tumor growth depends on receptor trans-signaling and thus, the evaluation of the combined expression pattern of all family members is of particular interest. This review presents the current evidence highlighting the role of the family as a whole panel and an update on the role of HER-3 and HER-4 receptors in breast cancer. Moreover, we provide updated data regarding the prognostic value of HER family members giving emphasis to novel methods for the determination of their status, such as real-time polymerase chain reaction. In addition, we review recent therapeutic approaches aimed at targeting the HER family in breast cancer patients.