HER2 overexpression in various tumor types, focussing on its relationship to the development of invasive breast cancer

To date, poor standardization in HER2 status evaluation has precluded reliable comparison of overexpression rates in different tumors. However, standardized methodologies have been introduced recently for these analyses, and have identified frequencies of 51%, 44%, 26% and 25% in Wilm's tumor, bladder, pancreatic and breast carcinoma, respectively. Other tumors tested had frequencies below 20%. The frequency was greater than that predicted by gene amplification data in some tumor types, which may indicate overexpression due to gene deregulation, rather than gene amplification. Analysis of a large retrospective series of breast carcinomas demonstrated an association between HER2 positivity and a number of other prognostic markers. Together, these variables identify a subset of tumors with poor prognosis and early relapse post-surgery. HER2 expression is relatively stable, with 95% concordance between the HER2 status of primary and metastatic lesions. However, contralateral tumors are unrestricted with regard to HER2 status. Preliminary data indicate that the HER2 status of a hormone receptor-positive tumor may fluctuate according to the menstrual cycle. It is anticipated that the emerging wealth of standardized data for HER2 status will help to elucidate the role of HER2 in tumor progression.