Genomic instability in histologically normal breast tissues: implications for carcinogenesis.

Abstract

Breast cancer is an important contributor to morbidity and mortality in society, but factors that affect the cause of the disease are poorly defined. Genomic instability drives tumorigenic processes in invasive carcinomas and premalignant breast lesions, and might promote the accumulation of genetic alterations in apparently normal tissues before histological abnormalities are detectable. Evidence suggests that genomic changes in breast parenchyma affect the behaviour of epithelial cells, and ultimately might affect tumour growth and progression. Inherent instability in genes that maintain genomic integrity, as well as exogenous chemicals and environmental pollutants, have been implicated in breast-cancer development. Although molecular mechanisms of tumorigenesis are unclear at present, carcinogenic agents could contribute to fields of genomic instability localised to specific areas of the breast. Understanding the functional importance of genomic instability in early carcinogenesis has important implications for improvement of diagnostic and treatment strategies.