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

Abstract

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 (G0) 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 paired 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 (P less than 0.05), and tumour: normal tissue ratios ranged from 1.27 to 8.30. Where doxorubicin concentration was expressed in terms of the relative cellularity of the tissues, there was no significant difference between, drug concentrations in the tumour and those in normal breast tissue (tumour: normal ratios, 1.1:1.8). There was a significant correlation (r = 0.76, P less than 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.