THE CONTROL AND BIOLOGICAL IMPORTANCE OF INTRATUMORAL AROMATASE IN BREAST-CANCER

The existence of aromatase activity in human breast Carcinomas has bee n established for about 20 years but the clinical and biological impor tance of this remains unclear. A number of studies in clinical materia l suggest that aromatase activity may be a prerequisite of response to aromatase inhibitors and that aromatase activity may be enhanced in t hose tumours relapsing during treatment with one such inhibitor, amino glutethimide. These results would carry more significance, however, if it was demonstrable that the growth of breast carcinomas is affected by the conversion of androgens to oestrogens by intratumoural aromatas e. We have tried to address this by establishing model systems with ar omatase-transfected MCF7 breast cancer cells. We have demonstrated tha t these cells can be stimulated mitogenically with androgen and that t his proliferation is suppressible with aromatase inhibitors. Similarly the growth of aromatase transfected cells but not wild type cells as xenografts is supported by androstenedione and inhibitable by both the steroidal aromatase inhibitor, 4-hydroxyandrostenedione and the non-s teroidal inhibitor, CGS 20267. Work with the former of these, which is a suicide inhibitor allowed us to demonstrate that growth can proceed with aromatase activity approximating to the highest level seen in br east carcinomas indicating that at least at this extreme level the int ratumoural conversion of androgens to oestrogens may indeed be able to support tumour growth. Further work with this model system should all ow us to define the minimal amount of intratumoural activity which can support tumour growth.