HISTOCULTURE DRUG RESPONSE ASSAY, A POSSIBLE EXAMINATION SYSTEM FOR PREDICTING THE ANTITUMOR EFFECT OF AROMATASE INHIBITORS IN PATIENTS WITH BREAST-CANCER

Histoculture drug response assay (HDRA) systems have been used in eval uating the cytotoxic effects of chemotherapeutic agents for many kinds of advanced cancers. We have adapted the HDRA system to estimate the antitumor effect of aromatase (estrogen synthetase) inhibitors on brea st cancer. Small pieces of breast cancer tissue specimens were placed onto a collagen-matrix filled with medium containing testosterone (a s ubstrate for aromatase) or testosterone plus an aromatase inhibitor. A t the end of culture, [3H]-thymidine incorporation was measured in ali quots of the histocultured specimens after 10 days culture. The increm ent of thymidine incorporation in testosterone-treated specimens to th at of control provides an index of existence of aromatase and estrogen -dependency, since converted estradiol from added testosterone by arom atase stimulates the incorporation. The decrease in the index of ''tes tosterone + aromatase inhibitor'' / ''testosterone'' indicates the ant itumor effect of the aromatase inhibitor on breast cancer. Twenty-one of 25 breast cancer surgical specimens were successfully cultured, and 6 showed the increased incorporation of [3H]-thymidine by testosteron e. Aromatase inhibitor blocked this stimulation in these 6 specimens. These results suggested that this antitumor effect is related to the i nhibition of aromatase and lthe aromatase inhibitor would be effective for individual patients with breast cancer which responds to testoste rone in this histoculture assay system. The histoculture technique we used here is therefore expected to be useful in predicting the efficac y of aromatase inhibitors for individual patients with breast cancer.