Distribution of doxorubicin to normal breast and tumour tissue in patients undergoing mastectomy

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Abstract
Summary Response to cytotoxic agents is assumed to be related to the concentration of drug achieved within tumour tissue. It is also often assumed that, given similar tissue concentrations of drug, normal tissues are less responsive to the same cytotoxic agents. This can partly be explained by the number of cells in normal tissues that are differentiated. These non dividing cells, in a stable testing phase of the cell cycle (Go) are less susceptible to cytotoxic damage. Little is actually known about the relationship between tumour drug concentrations and those in the tissue of the tumour-bearing organ. In this study, we compared doxorubicin concentrations in paried samples of tumour and normal breast tissue from 17 previously untreated women undergoing mastectomy. The relative cellularities of both specimens were estimated by measuring their DNA content. There was wide variation in intra-tumoural doxorubicin concentrations (range, 220–1,590 ng/g). Normal tissue also showed marked inter-patient variation (range, 81–1,000 ng/g). For a single patient the tumour drug concentrations were significantly higher than those in normal breast tissue (Pr=0.76,P<0.05) between peak serum values and tumour concentrations of drug. No correlation was found between drug concentrations achieved and the histological grade or oestrogen receptor status of the breast cancer.

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