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November 1987

The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen TherapyImplications for Treatment and Protocol Planning

Author Affiliations

From the Department of Surgery, Division of Surgical Oncology, Oregon Health Sciences University, Portland. Dr Pommier is a recipient of the Armand Hammer Travel Award for the 1987 meeting.

Arch Surg. 1987;122(11):1311-1316. doi:10.1001/archsurg.1987.01400230097017

• Fifteen patients whose tumors progressed while they received tamoxifen citrate therapy were studied by serial determinations of serum levels of estrone (E1), estradiol (E2), and dehydroepiandrosterone (DHEA) obtained during progression after withdrawal from tamoxifen therapy and total endocrine ablation or suppression. Discontinuation of tamoxifen therapy resulted in reductions of DHEA, E1, and E2 levels by 44%, 49%, and 42%, respectively. Ablation or suppression reduced sex steroids to minimal levels and produced responses in all patients. Elevations of DHEA, E1, and E2 could be provoked by readministering tamoxifen to hypophysectomized and oophorectomized, but not adrenalectomized, patients, indicating that the adrenal gland is the source of these sex steroids. We conclude that tamoxifen stimulates adrenal production of DHEA, which is aromatized to E2 and E2. Buildup of E1 and E2 overwhelms the competitive binding of tamoxifen to the estrogen receptor, resulting in tumor progression.

(Arch Surg 1987;122:1311-1316)