Haybaeck - Mechanisms of Molecular Carcinogenesis – Volume 2

(1)

(2)

Breast cancer (BC) is the most common cancer in women, accounting for more than 1,500,000 cases worldwide annually. In 2012, the incidence rate was 1,676,000 []. BC constitutes a heterogeneous group of different tumors characterized by variable clinical and morphological features with distinct molecular alterations/aberrations. The traditional classification of BC is based upon the assessment of histological type and grade. Patients age, tumor size, and lymph node status are also included in risk stratification and clinical treatment decisions. Immunohistochemical (IHC) analysis of receptor status on routinely processed tissue samples, namely, (1) expression of estrogen receptor (ER), (2) progesterone receptor (PR), and (3) overexpression/amplification of the human epidermal growth factor receptor 2 (HER2), also termed erythroblastosis oncogene B2 (ERBB2), is an imperative for complete pathological assessment, and their expression is the most important determinant of systemic treatment. The scoring of hormone receptors gives a better insight into potential response to endocrine treatment, and treatment with the humanized monoclonal antibody trastuzumab is largely dependent on the presence of HER2 either by immunohistochemistry or by in situ hybridization methods. Nonetheless, because of the genetic heterogeneity of breast cancers, histologically similar tumors may show different behaviors and responses to systemic therapies.

In the last two decades, different techniques have been used to collect molecular data on BC. By means of microarray-based gene expression profiling, the concept of heterogeneity among BCs has been established, demonstrating the need for distinct therapeutic approaches even further. More recently, next-generation sequencing (NGS) has brought new insights into BC classification. Prognostic and predictive subgroups have been suggested in order to enable individualized therapy [].

Here, we review histological features of ductal carcinoma in situ (DCIS) and histological subtypes of invasive BCs and current state of their molecular classifications and discuss the biological processes that are likely to play a role in BC carcinogenesis. Special subtypes and familial BCs will also be discussed, as well as future perspectives.

The human breast is composed of a branching duct system of 1520 lobes separated by fatty tissue. The terminal duct lobular units (TDLU) are the functional units of the breast and consist of the intralobular duct, ductules, and lobules that are lined by a single layer of cuboidal epithelium (luminal epithelium) supported by underlying basal/myoepithelial cells. The IHC profile of these cells differs: luminal epithelial cells can be highlighted by low molecular weight keratins, such as CK8, 18, and 19, whereas basal/myoepithelial cells stain with antibodies against p63, smooth muscle actin (SMA), smooth muscle myosin, calponin, S100-protein, CD10, CK5/6, etc. (Fig. ].