Effects of letrozole as primary medical therapy on in situ oestrogen synthesis and endogenous oestrogen levels within the breast

In situ aromatase activity and endogenous levels of oestrone and oestradiol were measure in breast tumours from 11 postmenopausal women with large primary oestrogen receptor positive breast cancers before and after three months systemic therapy with letrozole (2.5 mg daily). Patients were infused before and after treatment with 3ʹH androstenedione (20MBq) and 14C oestrone (1MBq) for 18 hours immediately before surgery. Oestrogens were purified from excised tumours and peripheral plasma. In situ aromatase activity was assessed by determining the relative amounts of 3H and 14C in the purified fractions and endogenous oestrone and oestradiol measured by immunoassay. One tumour showed no evidence of in situ oestrogen synthesis both before and after treatment; of the remaining 10 tumours, nine displayed a marked decrease in activity with treatment, the effect being statistically significant (P = 0.022 by sign test). Endogenous levels of oestrogen (oestradiol + oestrone) also fell with treatment in all 10 tumour pairs examined. These results indicate that systemic therapy with letrozole significantly inhibits in situ oestrogen synthesis and decreases endogenous levels of oestrogen within the breasts of postmenopausal women.