c-erbB-2 in breast cancer: development of a clinically useful marker

Abstract

c-erbB-2 amplification and/or overexpression occurs in 20% to 30% of breast cancers and appear to be associated with a more aggressive phenotype. Detecting abnormalities in c-erbB-2 might provide important clinical information for breast cancer patients. However, several of the potential clinical uses of c-erbB-2 remain unproven. Many variables influence c-erbB-2 results, including selection and characteristics of test populations and methods of analysis. Current literature suggests two roles for c-erbB-2, either as a pure prognostic factor with no association with therapy or as a factor predictive of benefit from specific types of systemic treatments. c-erbB-2 appears to be only a weak prognostic factor, although some individual studies suggest greater prognostic importance. c-erbB-2 abnormalities appear to predict for relative, but not absolute, resistance to endocrine therapy in estrogen receptor (ER)-positive women. When adjuvant chemotherapy is indicated, some studies have indicated that patients with c-erbB-2-positive cancers (by immunohistochemistry [IHC] or fluoresence in situ hybridization [FISH]) receive more benefit from anthracycline-containing regimens as compared to alkylating agents. c-erbB-2 testing appears critical for selecting patients with metastatic disease who should receive the anti-c-erbB-2 antibody, trastuzumab. Prospective randomized clinical trials of trastuzumab as adjuvant therapy are underway. Well-designed, prospective, randomized clinical trials (designed to test the value of c-erbB-2) or formal meta-analyses will help to better establish the predictive role of c-erbB-2 in breast cancer.