Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide therapy

Abstract

Aminoglutethimide (AG) is an effective chemical ablative form of therapy for metastatic breast cancer in postmenopausal women. Estrogen receptor (ER) status in breast cancer is useful in predicting the response to the hormonal treatments. Of 134 postmenopausal metastatic breast cancer patients treated with AG, ER analysis was done in 63 patients, 52 of whom are now evaluable. ER biopsy was performed prior to Ag therapy in 61 patients, but the results were not known to the investigators. ER value greater than or equal to 10 fmol/mg cytosol protein was considered ER positive (ER+), 4-9.9 fmol/mg borderline, and less than 4 fmol/mg ER negative (ER-). In 38 ER+ patients, objective response rate was 50% (three complete response, 16 partial response) and eight stabilization. Median duration of objective response was 15 months. Forty-three percent of the patients with borderline estrogen receptor level responded objectively (three partial response) with the median duration of response eleven months. Fourteen percent of ER- patients responded objectively (one complete response). Hence the estrogen receptor level predicts response in ER+ and ER borderline patients treated with AG.

Second Line Hormonal Therapy with Aminoglutethimide in Metastatic Breast Cancer

“…The results of our trial indicate that aminoglutethimide is an effective treatment modality for metastatic breast cancer. Several reports have shown response rates ranging between 16% and 50% (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)20), similar to our response rate of 34%. The highest rates were achieved when patients with positive hormone receptors were selected (20).…”

“…Although initial toxicity of aminoglutethimide was high (70%), most side effects were transient, as similarly reported in other series (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)20).…”

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

“…Combination endocrine therapy has not been shown to produce an increase in response rates (Tormey et al, 1976;Ward, 1977), but if only a subgroup of patients benefit, then the numbers in most trials have been too small to detect even a 2-fold difference with 90% confidence. Many of the non-responders will be oestrogen receptor negative, but only 50% of oestrogen receptor positive patients respond to first line endocrine therapy or to endocrine therapy with AG (Lawrence et al, 1980). Some of these oestrogen receptor-positive patients may fail to respond because of inadequate manipulation of the endocrine environment.…”

Medical adrenalectomy in patients with advanced breast cancer

“…These data confirm the apparent correlation noted in previous re-7.18. 24 and support the impression that tumor inhibition produced by aminoglutethimide is mediated via an endocrine mechanism. In addition, the response to medical adrenalectomy accurately predicts response to subsequent surgical adrenalectomy.…”