Significance of aromatase activity in human breast cancer.
The significance of in vitro aromatization of [7 alpha-3H]testosterone to estradiol by human breast cancer has been investigated by correlation with (a) estrogen receptor activity and (b) clinical response to endocrine therapy. Evidence for estradiol synthesis was obtained in 66 and estrogen receptor activity in 81 of 110 tumors. Whereas most estrogen receptor-positive tumors synthesized estradiol, the majority of the receptor-negative tumors did not. This tendency for aromatization to be associated with estrogen receptor-positive tumors was statistically significant (p less than 0.005). Mean level of receptor was also significantly higher in tumors with aromatization than in tumors without estradiol synthesis (p less than 0.001). Forty patients with advanced breast cancer have been treated by endocrine therapy. There was a significant trend for tumors with aromatization to be associated with response to treatment (p less than 0.05), but the correlation was not absolute and may simply reflect the association between aromatase activity and estrogen receptors. Within the small subgroup of patients treated with aminoglutethimide or adrenalectomy, tumors with high aromatase activity responded whereas those without aromatization did not. Tumor estrogen biosynthesis may therefore be of clinical significance in selecting patients for treatments which remove sources of precursor for aromatization of inhibit aromatase activity itself.
D000315:Adrenalectomy; D000616:Aminoglutethimide / Q000627:therapeutic use; D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis; D004964:Estriol / Q000096:biosynthesis; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D013739:Testosterone / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D000616:Aminoglutethimide; D013739:Testosterone; D004958:Estradiol; D010088:Oxidoreductases; D001141:Aromatase; D004964:Estriol