Molecular lesions involved in the progression of a human breast cancer.

Specific genetic alterations are observed in human breast cancer, but little is known about when these occur in the evolution of the disease. Three breast cancer effusions that occurred sequentially in a single patient were examined. Common cytogenic abnormalities were found in all effusion samples suggesting a single progenitor metastatic cell. Only the last effusion, however, exhibited a mutation of the c-K-ras gene and a loss of heterozygosity at the c-H-ras locus. These specific genetic abnormalities detected in the last effusion was correlated with improved in vitro growth of the primary cells, and with the ability to establish breast cancer cell lines. Thus a mutant ras gene and the loss of heterozygosity at the c-H-ras locus were associated with a more aggressive tumor phenotype occurring late in the course of this patient's disease and not with the initiation of the primary breast cancer, or in the establishment of metastases.