The progression of pre-invasive to invasive cancer

Most human invasive carcinomas are thought to evolve through a series of increasingly abnormal stages over many years, decades in most cases. In general terms, the stages are often referred to as hyperplasia, atypical hyperplasia, and carcinoma in situ. The transition from one stage to the next is primarily dependent on the accumulation of random genetic mutations in epithelial cells, so progression is non-obligatory. It is becoming clear that other forces are also at play, such as alterations of epigenetic gene regulation, and adjacent stromal cells promoting tumor progression, among others, which we are only beginning to understand. Carcinoma in situ is a late stage of tumor progression, and the immediate precursor of invasive disease. In this setting, carcinoma means that there is an ab-normal increase in the growth of tumor epithelial cells which accumulate in their normal environment (e.g. within ducts and lobules of the breast), but they do not invade out into the surrounding stroma or beyond. This chapter will discuss the development of invasive breast carcinomas (IBCs) as an example of the evolution of malignant epithelial neoplasms in general (Fig. 5.1). The general principles of the development and progression of invasive carcinomas are similar in many solid organs, although specific details may vary.