Correlation of breast tumour aromatase activity and response to aromatase inhibition with aminoglutethimide.
Tumour aromatase, oestrogen (E) and progesterone (P) receptor (R) measurements were carried out in biopsies from 29 patients with advanced or recurrent breast cancer. Patients were then treated with aminoglutethimide according to one of two dosage regimens: (a) aminoglutethimide 1000 mg/day + hydrocortisone 20 mg/day, and (b) aminoglutethimide 250 mg/day. Tumour aromatase values varied from 0.05 to 2.07 pmol ER produced/mg protein/h and ER and PR values from less than 1 to 249 and less than 1 to 132 fmol of steroid bound/mg protein, respectively. There was no correlation between aromatase values and either ER or PR and also no correlation between ER and PR and response to aminoglutethimide. Tumour aromatase values did however correlate with response to treatment. Mean aromatase levels for responders (1.18 +/- 0.64 pmol E produced/mg protein/h) were significantly higher than those of non-responders (0.34 +/- 0.27) (t = 5.20, DF 27; p less than 0.005). Ten out of fourteen patients with aromatase values greater than 0.5 pmol ER produced/mg protein/h responded, whereas 0 out of 15 patients with tumour aromatase values less than this responded. Responses were seen at both dosages of aminoglutethimide. It is concluded that tumour aromatisation will be a useful measurement in predicting response to aromatase inhibitors.
Bezwoda
W R
WR
Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Mansoor
N
N
Dansey
R
R
D000616:Aminoglutethimide / Q000494:pharmacology / Q000627:therapeutic use*; D001141:Aromatase / Q000032:analysis*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004341:Drug Evaluation; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
D047072:Aromatase Inhibitors; D004967:Estrogens; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000616:Aminoglutethimide; D001141:Aromatase