Molecular pathogenesis of bilateral breast cancer.

Bilateral breast cancer (biBC) offers intriguing possibilities for molecular genetic investigations, however it is disproportionally less studied than its unilateral counterpart. By now, genetic research has succeeded to resolve at least two important aspects of biBC pathogenesis. First, it has been confirmed, that the vast majority if not all biBC arise due to clonally independent events but not due to contralateral metastatic spread. Second, unselected biBC cases have been shown to have a modest prevalence of BRCA germ-line mutations (approximately 5%), although a considerable frequency of BRCA defects (up to 20%) has been observed in early-onset and/or familial forms of the disease. Other data related to biBC appear to be at suggestive stage. Recent reports demonstrate, that the tumors forming biBC pair may show similarities of their molecular portraits, especially if they develop synchronously. This observations imply that the host factors may determine not only the level of breast cancer susceptibility, but also the molecular variant of the disease development. Apart from this, biBC may serve as a very demonstrative case group in the studies of breast cancer predisposing low-penetrance gene polymorphisms, because it is more likely to accumulate unfavorable allele combinations than the unilateral patients. The utility of this approach has been already exemplified by several scientific publications. Further research on the biBC molecular pathogenesis may significantly contribute to the general understanding of the process of malignant transformation.