INTRATUMORAL HETEROGENEITY FOR AMPLIFIED GENES IN HUMAN BREAST-CARCINOMA

Intratumoral heterogeneity was studied in human breast cancer by examining separate tumor lesions of individual patients. Tumor samples were obtained from each patient by fine-needle biopsies from 2 to 4 separate tumor lesions. We used a semi-quantitative PCR to distinguish between samples with gene amplification and single gene copy samples. Five genes were analyzed in each biopsy: MDR-1, dihydrofolate reductase, thymidylate synthase, c-erb-B2 and int-2. Three groups of patients were examined: those awaiting initiation of treatment; those receiving first-line endocrine therapy; and those receiving second-line endocrine treatment. A pattern of intratumoral heterogeneity for gene amplification was clearly apparent. The frequency of amplification was lowest before initiating therapy and highest in patients receiving second-line treatment (p = 0.023). (C) 1994 Wiley-Liss, Inc.