CLINICAL IMPORTANCE OF INTRATUMORAL AROMATASE

Evidence to support the contention that estrogen biosynthesis in breas t cancers is of clinical significance has been sought by relating acti vity to (i) clinical response to aromatase inhibitors and (ii) tumor c oncentrations of estrogens, Significant correlations have been reporte d between the presence/high levels of tumor aromatase in vitro and lik elihood of response to aminoglutethimide in patients with advanced bre ast cancer, but the association is not absolute and it has been more d ifficult to demonstrate similar relationships in patients with earlier stages of cancers treated with other more potent inhibitors. There ar e however data to suggest that in vitro measurements of aromatase may not reflect in situ estrogen synthesis, For example mammary adipose ti ssue fibroblasts preincubated with reversible aromatase inhibitors may paradoxically display elevated in vitro aromatase activity. Similar e nhanced in vitro activity map be observed in breast material taken fro m patients treated neo-adjuvantly with aromatase inhibitors such as am inoglutethamide and letrozole. That this is an artifact of in vitro sy stems can be demonstrated by performing in situ assessments of aromata se activity in patients before and after treatment with aromatase inhi bitors, Thus it can be shown that letrozole markedly inhibits in situ aromatase and reduces tumor levels of estrogens.