RELATIONSHIP BETWEEN TUMOR AROMATASE-ACTIVITY, TUMOR CHARACTERISTICS AND RESPONSE TO THERAPY

Aromatase activity has been measured in human breast cancers by incubating tumour minces with [7-alpha-H-3]testosterone and characterizing purified oestradiol (E2) fractions by chemical derivative formation. Of 247 primary tumours, 178 showed evidence of oestrogen biosynthesis, levels varying between 0.5 and 12.5 fmol E2 produced/h/g tissue. These values were quantitatively small but at least comparable with those in other peripheral tissues. There was no correlation between presence or level of aromatase activity and the histopathology of the tumours although oestrogen biosynthesis was more likely to be present in more cellular tumours. Aromatase activity was also unrelated to age, menopausal status, lymph node status and T stage of the patient from which the tumour was derived. In a subgroup of patients presenting without clinical evidence of distant metastatic disease, no significant relation was detected between tumour aromatase and disease-free interval, but tumours without aromatase activity were associated with increased survival at 36 months after primary treatment. A statistically significant correlation was also detected between the presence of tumour aromatase and oestrogen receptors. Furthermore, in small subgroups of patients with "advanced" breast cancer tumour aromatase was related to response to aminoglutethimide but not tamoxifen therapy. Whilst these results do not conclusively define a role for local synthesis of oestrogen in the progression of breast cancer, this possibility still exists and further studies on tumour aromatase are warranted.