When is a tumor marker ready for prime time? A case study of c-erbB-2 as apredictive factor in breast cancer

Purpose: c-erbB-2 (HER-2, c-neu) might play a role as a predictive factor i n breast cancer. However, the clinical utility of the marker in this diseas e is still not established. We conducted a critical analysis of the literat ure, in which we reviewed the factors that contribute to the lack of accept ance of c-erbB-2 for clinical use and attempted to determine the predictive role of c-erbB-2 for response to specific therapies. Methods: We conducted a MEDLINE literature search using the keywords c-erbB -2, HER2, neo, and breast cancer, reviewed the references included in each publication, and reviewed abstracts that have been reported in the 1997-200 0 proceedings to the American Association of Cancer Research and American S ociety for Clinical Oncology annual meetings. Results: The preclinical and clinical data reported to date suggest that am plification or overexpression of c-erbB-2 is a weak to moderate negative pu re prognostic factor, c-erbB-2 seems to be a weak to moderate negative pred ictive factor for response to endocrine therapy. The marker is also a moder ate negative predictive factor for response to alkylating agents and a mode rate positive predictive factor for response to anthracyclines. The data re garding response to taxanes or radiotherapy are not sufficient to make reco mmendations regarding treatment decision making. Finally, c-erbB-2 is a str ong predictive factor for response to trastuzumab, Conclusion: We conclude that, in the adjuvant setting, c-erbB-2 status shou ld not be used to determine whether a woman should receive adjuvant systemi c therapy (weak prognostic factor). In addition, c-erbB-2 status should not be used to determine whether a patient should receive endocrine therapy. W hen adjuvant chemotherapy is recommended, anthracycline-based therapy shoul d be the preferred regimen for c-erbB-2-positive patients. However, when an thracyclines are contraindicated, alkylating agent-based therapy should not be withheld, To determine the true predictive role and strength of the mar ker for response to each therapy, prospective randomized clinical trials or formal meta-analyses are required. (C) 2001 by American Society of Clinica l Oncology.