Prognostic and predictive significance of HER2 in breast cancer

In recent years, there has been increased understanding of molecular aberrations responsible for or accompanying breast carcinogenesis. Particular attention is paid to human epidermal growth factor receptor family including HER2. Increased expression or amplification of HER2 has been demonstrated in 10-40% of breast cancer patients. This feature is associated with more aggressive tumor behaviour, expressed by shortened time to progression and overall survival, mainly in node-positive patients. Studies of HER2 status and prognosis in node-negative patients have yielded conflicting results. It is suggested that combining HER2 measurement with other conventional prognostic markers, such as tumor size, histologic grade, steroid receptor and nodal status, will allow for selecting high risk patients. Although HER2 overexpression is the most important predictor of trastuzumab treatment efficacy, its predictive role for other systemic therapies still remains controversial. Available studies indicate a benefit from anthracycline-based schedules irrespective of HER2 status. In contrast, in some studies CMF has proven less effective in HER2 positive tumors. There is also some evidence that HER2 status is a possible indicator of hormone resistance. However, the clinical data are contradictory and there are studies, which analysed large numbers of patients and found no significant association or even a trend toward an association between HER2 status and response to hormonal therapy. This issue will only be resolved with large-scale, long-term prospective studies. Possible prognostic/predictive significance of HER2 status necessitates the development of an accurate and consistent method of its assessment. Numerous techniques have been used, predominantly based on HER2 overexpression or gene amplification. In most studies to date, HER2 status has been determined retrospectively using fresh frozen or paraffin embedded tissue employing immunohistochemistry. It is the most widely used and practical assay, available in most laboratories and routinely used for selection to trastuzumab therapy. Recent studies have demonstrated the superiority of FISH method and its standard application has been suggested. However, a minority of pathology laboratories are set up to assay HER2 status using FISH and it is also relatively time consuming and complicated to perform.