Carcinogenesis of Breast Cancer : Advances and Applications

Breast cancer is the most common malignancy among women with an increasing incidence attributable to modern lifestyle and hormone replacement therapy. Despite rapid progress in understanding tumorigenesis, limited is the translation of discovery-based preventive research into clinical use. Germ-line mutations in BRCA1 and BRCA2 genes, identified a decade ago, account for 25% only of familial risk and research has been focused on searching the other highand low-penetrance genes responsible for the remaining 75%. Receptor tyrosine kinases (RTKs) are subclass of cell-surface growth-factor receptors. Deregulation of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling has a key role in tumorigenesis and angiogenesis of human cancers including breast cancer. The discovery of the HER2 gene revealed that its amplification is involved in carcinogenesis, led to the development of target-specific therapy (monoclonal antibody trastuzumab) and opened the door for the evaluation of other RTKs, which may be proven potential targets for chemoprevention. Breast carcinoma is biologically heterogeneous. Genomics and proteomics approaches such as gene-array, tissuearray, single-nucleotide-polymorphism analysis and protein expression will improve the understanding of molecular mechanisms, the classification of individuals into lowand high-risk of cancer and will facilitate the discoverybased research for the development of novel targeted preventive interventions. Identifying genetic and environmental factors involved in tumorigenesis and understanding signaling pathways appears to be the most rational approach for breast cancer prevention. ntroduction Breast cancer results from genetic and environmental factors, that both are involved, with the relative importance of each ranging from strongly genetic, or strongly environmental, leading to the accumulation of mutations in essential genes. Breast cancer can be divided into: Inherited (familial) and sporadic cancer. Criterion is the presence or absence of breast cancer family history respectively, in-situ (pre-invasive lesions: (ductal carcinoma in situ DCIS and lobular carcinoma in situ (LCIS) and invasive breast cancer. Criterion is the invasion beyond the epithelial basement membrane into the adjacent breast stroma (invasive) or not (in situ). Incidence and Time Trends Breast cancer incidence increases particularly in the Western world. In the USA, 215,990 new cases are expected in 2004; of these cases 59,390 are in situ carcinoma (27.8%), Time trends data suggest dramatic increase of carcinoma in situ, that is attributable rather to a better detection of DCIS due screening mammography. Breast cancer accounts for 32% of all cancer cases among women in 2004 and is the most common malignancy in women. The risk is increasing even among BRCA1 and BRCA2 mutation carriers over the last decades (women born after 1940 have a higher lifetime risk). In situ breast carcinoma has risen dramatically. DCIS has been increased by a factor 12 in the past two decades, from 4800 cases in 1983 to 59,390 in 2004 in Gastric Breast Cancer 2004; 3(1): 13-22