Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer

Abstract

Summary Eighty-one postmenopausal women with advanced breast cancer were studied for the effects of treatment with aminoglutethimide (AG) plus hydrocortisone on peripheral hormones and response to therapy. There were 40 responders (R) and 41 non-responders (NR) at 3 months from the start of treatment. Plasma oestrone concentrations were higher in non-responders at 1 and 2 months after starting AG (Means: NR 106+50, R 84+26pmoll1-, P<0.05; highest value NR 121+51, R 99+24pmoll1, P<0.05). High oestrone levels were correlated with bulky liver secondaries, but not with age, tumour-free interval, time from last menstrual period, time from relapse to start of AG or body weight. Non-responders had higher mean prolactin levels on treatment (prolactin <SOOmIUl-l in 14/40 NR, 2/35 R, P<0.01). High oestrone or prolactin levels were present in 28/41 NR and 6/40 R (P<0.001). Dehydroepiandrosterone sulphate suppression did not differ between R and NR. The differences in peripheral endocrine environment in non-responding patients suggest that oestrogen metabolism may differ in non-responding patients and that sub-groups could be selected for rational endocrine therapy.

Endocrine and clinical consequences of combination tamoxifen – aminoglutethimide in postmenopausal breast cancer

“…Gonadotrophin levels were suppressed and SHBG levels were increased. Tamoxifen has been found to cause such typically oestrogenic changes (Coombes et al, 1982;Willis et al, 1977;Sakai et al, 1978) whilst aminoglutethimide+hydrocortisone has little effect on gonadotrophins but may also increase SHBG levels (Harris et al, 1983a). Oestrone, oestradiol and DHAS levels were suppressed to levels similar to those found in our previous studies of aminoglutethimide + hydrocortisone (Harris et al, 1983a, b).…”

“…In two earlier studies of aminoglutethimide + hydrocortisone in advanced breast cancer no difference in pretreatment levels of DHAS was observed between responders and nonresponders (Harris et al, 1983a;Santen et al, 1982). However, a similar difference between responders and non-responders was observed in ontreatment samples from one of these studies (Santen et al, 1982 The difference between responders and nonresponders in pretreatment DHA-S levels is less easily explained.…”

“…All (Harris et al, 1983a); DHAS, (Harris, et al, 1982); androstenedione, (Dowsett et al, 1984); prolactin, (Dowsett et al, 1983)]. Cross-reaction of tamoxifen in the oestradiol and oestrone assays was 10-4% and 10-3% respectively.…”

Zoladex: Endocrine and therapeutic effects in post-menopausal breast cancer

“…It is interesting to note that the patient with the best response of longest duration showed the greatest fall in oestradiol levels. There was no general correlation of hormone suppression with response, and this has been noted for other hormone suppressive therapies (Santen et al, 1982;Harris et al, 1983b).…”

Aminoglutethimide – A New Endocrine Therapy in Breast Cancer

“…In non-responders, the adre nal steroids DHAS and A4-androstenedione are ele vated compared with responders, and ocstrone levels are also higher. This may reflect stress in non-respond ers [33]. In the responders who relapse, oestronc plasma levels rise 1-2 months before clinical progres sion [34], This is unlikely to be the mechanism of relapse, but may be due to hormone produced by the tumour.…”