We have continued our efforts to identify and characterize frequent genetic changes associated with primary human breast tumor DNAs. The int-2 gene is related to the fibroblast growth factor gene family. It is frequently activated by mouse mammary tumor virus- induced insertional mutagenesis in mouse mammary tumors. We have found that int-2 is amplified 2- to 15-fold in 16% of human breast tumors (n=118). This genetic alteration has a highly significant association (P less than or equal to 2 x 10-6) with patients who subsequently developed a local recurrence or distal metastasis. The c-erbB-2 gene is related to the gene encoding the epidermal growth factor (EGF) receptor. We found that 10% of the breast tumor DNA contain an amplification of c-erbB-2. In contrast to one published report from another laboratory, we did not find a significant association between this mutation and the patients' prognosis.