Pathology and Molecular Pathology of Breast Cancer

In this chapter, we introduce the reader to the embryological development of the mammary gland, together with its normal anatomy, histology, and physiology. The histopathologic features of benign conditions, including risk indicators and precursors of cancer, are then discussed, with a particular focus on the molecular underpinning of preinvasive lesions. The remainder of the chapter focuses on breast cancer, integrating morphological features with molecular pathology data. The contribution of high-throughput techniques is discussed with particular attention to their contribution to our understanding of the biology of breast cancer. It is now universally acknowledged that breast cancer does not represent a single disease. This concept was brought forth by the molecular classification devised by gene expression profiling analyses of invasive breast cancers. With the advent of massively parallel sequencing, the diversity of breast cancer has now also become evident even at base pair resolution. If on one side the molecular classification has provided a working model for breast cancer taxonomy largely embraced also by clinicians, surgeons, scientists and pathologists, we have to acknowledge that prognostication and therapy prediction for breast cancer patients is still currently largely based on accurate grading and staging, assessment of hormone receptors by immunohistochemistry and of HER2 status by immunohistochemistry and in situ hybridization. In the subgroup of ER-positive/HER2-negative disease, however, prognostic gene expression signatures have entered the daily practice and have a definite role in refining prognostication and clinical decision-making. Furthermore, massive parallel sequencing analysis of breast cancers has proven to be an ancillary method for the enrollment of patients with advanced disease into clinical trials.