The molecular pathology of human breast cancer.

Perhaps one of the most exciting recent developments in breast cancer research is the steadily increasing number of small screen detected lesions which are available for study. These samples will allow a number of questions of key importance to the development and progression of breast cancer to be answered. For example, the relationship between a variety of benign and premalignant lesions and frankly invasive breast carcinomas can be examined to determine the sequence of progression, if indeed such a sequence exists. Subtypes of screen detected lesions may be identified in which different genetic events have occurred, and the relationship between these genetic events and progression may be established. Such studies could identify groups of women for whom no further treatment is required or those for whom adjuvant therapy, radiotherapy or further surgery is indicated. A number of genetic alterations have now been identified that seem to be independent indicators of prognosis. Such alterations include overexpression of c-erbB2 and mutation of TP53. Although there is still some debate about the statistical significance of data from a number of different groups, it seems certain that the status of a number of genes will provide prognostic information to augment existing criteria. There is an urgent need for an examination of a large panel of breast tumours for a number of key genetic alterations and for a critical evaluation of all the changes to existing clinical variables such as clinical stage, grade, survival and relapse times and growth factor receptors. Molecular pathology is providing new and exciting insights into the pathogenesis of human breast cancer, and molecular events associated with inherited breast disease, early stages, progression and metastasis of breast cancer are now becoming better understood.