ERBB2 Oncogene in Human Breast Cancer and Its Clinical Significance

We reveiwed the relationships between ERBB2 amplification and/or overexpression in human breast cancer and the clinicopathological parameters described in the literature (97 studies involving 22,616 patients) in order to draw conclusions regarding its clinical interest. The mean of ERBB2 positivity (26%, ranging from 5 to 55%) is not dependent on the method used to evaluate ERBB2 amplification or overexpression. Despite the discrepancies observed between the different studies, several associations between ERBB2 positivity and the classical clinicopathological parameters were noted. There are clear relationships between ERBB2 positivity and the lack of steroid receptors, the histological subtypes of mammary tumours (ductal invasive and in situ), worse histological and nuclear grades, aneuploidy and high rate of proliferation. In univariate analyses, ERBB2 is strongly associated with poor prognosis. All these data indicate that ERBB2 is a marker of aggressiveness of the tumour. However, ERBB2 does not retain a clinical prognostic significance in multivariate analyses, since it is associated with several strong prognostic parameters. When considering the prognostic value of ERBB2 in relation to treatment, a significantly worse survival of the treated patients is noted in ERBB2 positive patients. This suggest that ERBB2 could be a marker of reduced response to chemotherapy and hormonal treatment. With respect to the tumour response to treatment, the results, provided as yet by pilot studies, remain controversial and further investigations are necessary to evaluate the predictive value of ERBB2. Finally, new therapeutic approaches targeting the cells overexpressing ERBB2 have been developed.