EFFECTS OF LETROZOLE AS PRIMARY MEDICAL THERAPY ON IN-SITU ESTROGEN SYNTHESIS AND ENDOGENOUS ESTROGEN-LEVELS WITHIN THE BREAST

In situ aromatase activity and endogenous levels of oestrone and oestr adiol were measure in breast tumours from 11 postmenopausal women with large primary oestrogen receptor positive breast cancers before and a fter three months systemic therapy with letrozole (2.5 mg daily). Pati ents were infused before and after treatment with H-3 androstenedione (20MBq) and C-14 oestrone (1MBq) for 18 hours immediately before surge ry. Oestrogens were purified from excised tumours and peripheral plasm a. In situ aromatase activity was assessed by determining the relative amounts of H-3 and C-14 in the purified fractions and endogenous oest rone and oestradiol measured by immunoassay. One tumour showed no evid ence of in situ oestrogen synthesis both before and after treatment; o f the remaining 10 tumours, nine displayed a marked decrease in activi ty with treatment, the effect being statistically significant (P = 0.0 22 by sign test). Endogenous levels of oestrogen (oestradiol + oestron e) also fell with treatment in all 10 tumour pairs examined. These res ults indicate that systemic therapy with letrozole significantly inhib its in situ oestrogen synthesis and decreases endogenous levels of oes trogen within the breasts of postmenopausal women.