Intratumoral heterogeneity for amplified genes in human breast carcinoma

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Abstract
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).