Doxorubicin gradients in human breast cancer.

Ten patients with locally advanced breast cancer were given doxorubicin i.v., and an incision biopsy was subsequently taken. Doxorubicin autofluorescence was examined using computerized laser scanning microscopy, and microvessels were immunostained in the same sections. Overlays of both pictures revealed doxorubicin gradients in tumor islets with high concentrations in the periphery and low concentrations in the center of the tumor islets. Gradients were most pronounced shortly after the injection, but they could still be detected 24 h later. No gradients were observed in connective tissue. This study demonstrates a serious risk of the drug not reaching all of the cancer cells in those cases in which the cancer cells are densely packed in islets. The efficacy of drug treatment will thus depend on the histology of the tumor tissue.