Genetic alterations in primary breast cancer.

A serious effort has been made to identify and characterize mutations that frequently occur during the evolution of primary human breast cancer. Some of these mutations involve amplification of protooncogenes (c-myc, c-erbB-2, and int-2) that have been shown to contribute to experimentally induced breast cancer in mouse model systems. Tumor development in mice containing the c-myc or c-erbB-2 transgene suggests that the cellular and developmental contexts in which the genes are expressed define their relative contribution to tumorigenesis. Homozygous deletions or loss of heterozygosity (LOH) represent another type of mutation that has been frequently observed on four chromosomes (1q, 3p, 11p, and 13q) in tumor DNA. They are thought to unmask recessive mutations (LOH) that inactivate or remove (homozygous deletion) suppressor genes that regulate normal cell proliferation. Attempts to determine whether specific mutations are associated with certain clinical parameters have led to the controversial hypothesis that some mutations may be useful prognostic indicators of the post-surgical course of the disease. The current results underscore the necessity for much larger, better control studies to unambiguously define the potential of such mutations as clinical markers.