Gastric & Breast Cancer
DOI: 10.2122/gbc.2004.0031

PERSPECTIVE

Carcinogenesis of Breast Cancer:
Advances and Applications

Niki J. Agnantis, MD, PhD, Michael Fatouros, MD, Ioannis Arampatzis, MD, Evaggelos Briasoulis, Eleftheria V. Ignatiadou, MD, Evangelos Paraskevaidis, MD, and Dimitrios Roukos, MD.

From the Departments of Pathology (NJA) Surgery (MF, IA, HB, EVE, DHR), Medical Oncology (EB), and Gynecology & Obstetrics (EP) at the Ioannina University School of Medicine, GR –45110, Ioannina, Greece.
Correspondence to: Dimitrios H. Roukos, MD, Ioannina University School of Medicine, GR –45110, Ioannina, Greece, or email:
droukos@cc.uoi.gr

Abstract Introduction Incidence, time trends Risk factors, estrogen Why does breast cancer incidence increase? BREAST CANCER GENETICS High-/low-penetrance genes Breast Cancer Pathways (Inherited, sporadic cancer) Receptor tyrosine kinase Conclusions References 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 high- and 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, tissue-array, single-nucleotide-polymorphism analysis and protein expression will improve the understanding of molecular mechanisms, the classification of individuals into low- and high-risk of cancer and will facilitate the discovery-based 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. .