A Randomized Trial Comparing Surgical Adrenalectomy with Aminoglutethimide plus Hydrocortisone in Women with Advanced Breast Cancer

Santen, Richard J.; Worgul, T. J.; Samojlik, E.; Interrante, Albert; Boucher, Alice E.; Lipton, Allan; Harvey, Harold A.; White, Daniel; Smart, Emma; Cox, Charles E.; Wells, Samuel A.

doi:10.1056/nejm198109033051003

Cited by 196 publications

(49 citation statements)

References 25 publications

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“…This has been previously suggested by demonstration of clinical responses to testololactone (Goldenberg et al, 1973) and aminoglutethimide (Santen et al, 1981) and recently confirmed by the demonstration of Right-hand column-breast cancer patients on AG:…”

Section: Discussionsupporting

confidence: 56%

“…Aminoglutethimide (AG) is a clinically effective endocrine treatment for advanced postmenopausal breast cancer (Lipton et al, 1974;Smith et al, 1978;Santen et al, 1981;Harris et al, 1982), in which it has been used almost exclusively in doses of 750-1000mgday-1, in combination with hydrocortisone (HC). This therapeutic regime was derived with the aim of suppressing adrenal androgen synthesis (Lipton et al, 1974;Wells et al, 1978) which was expected to result from previously reported inhibition by AG of the conversion of cholesterol to pregnenolone by 20,22-desmolase (Cohen, 1967;Dexter et al, 1967).…”

mentioning

confidence: 99%

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Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients

Dowsett¹,

Santner²,

Santen³

et al. 1985

Br J Cancer

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Aminoglutethimide without glucocorticoid has been shown to be a clinically effective treatment for postmenopausal breast cancer in low dosage (250 mg day-1). The mechanism of action of this approach is thought to be the inhibition of peripheral aromatase, the enzyme which converts androstenedione to oestrone. The activity of this enzyme was measured in vivo by injection with 3H-androstenedione and 14C-oestrone and found to be 0.20% +/- 0.05 in 5 patients on low dose AG therapy. In comparison with previously published data this demonstrates a 92% inhibition of peripheral aromatase activity confirming aromatase inhibition as a viable aim in the endocrine treatment of breast cancer.

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Section: Discussionsupporting

confidence: 56%

mentioning

confidence: 99%

Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients

Dowsett¹,

Santner²,

Santen³

et al. 1985

Br J Cancer

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“…However, it was found to cause adrenal suppression by inhibiting multiple cytochrome P-450 enzymes [30]. As adrenalectomy had been shown to be effective in treating breast cancer by Charles Huggins, Richard Santen and colleagues in the late 1970's began using aminoglutethimide as a medical approach to suppressing adrenal steroids in breast cancer patients [31][32][33]. Because aminoglutethimide inhibited a number of steroidogenic P-450 enzymes including CYP11, patients were given cortisol replacement.…”

Section: Efforts To Bring 4-oha Into the Clinicmentioning

confidence: 99%

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Jordan¹,

Brodie²

2007

Steroids

260

183

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The enthusiasm with which the clinical community has embraced the use of antiestrogenic therapy to treat breast cancer is based upon the proven record of success that first the nonsteroidal antiestrogen tamoxifen and then the aromatase inhibitor have demonstrated in clinical trial. The reasons for the enthusiasm are obvious. Antihormonal therapy, particularly aromatase inhibition to create a "no estrogen state" in the postmenopausal breast cancer patient is effective, saves women's lives, is contributing successfully to reducing the national mortality from breast cancer, is relatively cheap and has fewer side effects and easy administration (oral) than any other anticancer strategy. However, the successful application of a therapeutic strategy to block the known growth stimulation property of estrogen in breast cancer was not greeted with such enthusiasm 40 years ago.Estrogen is essential for life. Without the critical role of estrogenic steroids, reproduction would not be possible. Based on emerging knowledge from laboratory studies, the value of modulating the steroid environment during the menstrual cycle was advanced to clinical testing during the 1950's as a means of oral contraception. The results of these studies were to change society forever.The Worcester Foundation for Experimental Biology is the place where Gregory Pincus established the scientific principles necessary to propose clinical testing of the oral contraceptive and M.C. Chang subsequently established the first protocols to perform in vitro fertilization. Simply stated, the Worcester Foundation was, at that time, the world center for steroid endocrinology and reproductive biology. Over the years, hundreds of scientists have trained at the Foundation and subsequently spread their knowledge throughout the world [1]. However, fashions in research change and new opportunities emerge.In 1971, President Nixon made a national commitment to seek a cure for cancer by signing the National Cancer Act. Mahlon Hoagland, the President of the Worcester Foundation, responded to the initiative by appointing Professor Elwood V. Jensen, Director of the Ben May Cancer Research Laboratory at the University of Chicago, to be a member of the Foundation's Scientific Advisory Board. Jensen had discovered the estrogen receptor (ER) as the putative mechanism of estrogen action in its target tissues [2]. The known link between estrogen and breast cancer suggested that "antiestrogenic strategies" might have potential as therapeutic Correspondence to: V. Craig Jordan, v.craig.jordan@fccc.edu. Present Address: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be d...

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“…Originally developed as an anticonvulsant, but found to have the adverse effect of inducing adrenal insufficiency, it was introduced as a medical alternative to surgical adrenalectomy in postmenopausal patients and shown to be as effective as surgical ablation in a randomised trial (Santen et al 1981). Subsequent randomised trials showed it to be just as effective as tamoxifen in the treatment of metastatic breast cancer in post-menopausal women.…”

Section: Aromatase Inhibitorsmentioning

confidence: 99%

Endocrine aspects of the clinical management of breast cancer - current issues

Wyld¹,

Chester²,

Perren³

1998

Endocrine Related Cancer

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A Randomized Trial Comparing Surgical Adrenalectomy with Aminoglutethimide plus Hydrocortisone in Women with Advanced Breast Cancer

Cited by 196 publications

References 25 publications

Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients

Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Endocrine aspects of the clinical management of breast cancer - current issues

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