Standardization of immunobioassays as surrogate endpoints.

Despite centuries of scientific inquiry and medical effort, breast cancer remains one of the most dreaded human illnesses, emphasizing the need for prevention, early detection, and better management of these patients. Currently, newly recognized biomarkers are being examined as prognostic indicators to identify potentially aggressive cancers and to aid in planning treatment. Although the new prognostic factors are not yet firmly established, recent insights coupled with the availability of new biological markers have provided an opportunity to understand the initial genetic events leading to the development of breast cancer. Knowledge about those genetic events may provide opportunities for prophylactic intervention, improve our ability to predict breast cancer risk, and lead to strategies for early detection. Attention has focused on histomorphological changes and, to a lesser extent, cytomorphological changes in breast lesions associated with increased risk for subsequent breast cancer. However, the goal underlying the detection of early breast cancer is to distinguish patients who will develop breast cancer from those who will not. This task involves complex issues surrounding the selection, validation, quantitation, standardization, and population application of breast cancer biomarkers, and perhaps designing a protocol to control four major sources of cancer marker variability which may confound biomarker clinical application. These include biological and sampling diversity, variability of detection procedures, and validation against acknowledged disease endpoints. Immunocytochemistry has been applied extensively to assess the pattern of expression of different biomarkers in breast cancer. Immunocytochemical assays have permitted the localization of estrogen and progesterone receptors, oncogenes and tumor suppressor genes, growth factors, and other constituents at the cellular level, and also facilitated correlative analysis of morphology with specific expression of gene products.(ABSTRACT TRUNCATED AT 250 WORDS)