Breast cancer in the 21st century: Neu opportunities and neu challenges

Recent advances in the understanding of the molecular and genetic alteratio ns underlying breast cancer development and progression have provided the o pportunity to develop novel therapeutic strategies for this disease. None o f these developments has had a greater recent impact on clinicians and path ologists than the recognition of the importance of the HER-2/neu (c-erbB-2) oncogene, Located on chromosome 17, this gene encodes a 185 kD transmembra ne glycoprotein with tyrosine kinase activity that functions as a growth fa ctor receptor. Amplification or overexpression of HER-B/neu is seen in appr oximately 20 to 30% of invasive breast cancers and this has been considered to be an adverse prognostic factor in many studies. However, recent intere st in HER-2/neu has largely been focused on its role as a potential target for breast cancer treatment. In particular, recognition of the role of HER2 /neu in breast cancer growth led to the development of a humanized monoclon al antibody directed against the HER-2/neu protein as a therapeutic agent ( Herceptin). Clinical studies have further suggested that HER-2/neu status c an provide important information regarding sensitivity to certain forms of conventional systemic therapy, particularly anthracyclines, As a result of these developments, there has been increasing demand for pathologists to pe rform assays for HER-2/neu on current and archived breast cancer specimens. Immunohistochemistry and fluorescence in situ hybridization have emerged a s the most viable assays for evaluation of HER-2/neu in routine clinical pr actice. However, each of these methods has its advantages and disadvantages . Determining the relative merits of these assays and developing clinically meaningful and reproducible systems to report the results are challenges p athologists must now address,The development of a therapeutic agent that di rectly targets a protein involved in a growth-signaling pathway represents a new paradigm in breast cancer treatment. Therapeutic strategies that targ et other molecules involved in breast cancer development and progression ar e on the horizon, It is crucial that pathologists become aware of these adv ances and assume a pivotal role in the development and application of assay s to evaluate these new molecular targets.