title: High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy.
abstract: BACKGROUND
  Stage IV hormone-sensitive breast cancer is often treated with aromatase inhibitors (anastrozole, letrozole, exemestane), which block the conversion of dehydroepiandrosterone (DHEA) to estrone and estradiol. This is intended to obviate the need for steroid replacement and antiquate adrenalectomy.
  
  
  METHODS
  Patients who underwent oophorectomy and were being treated with new aromatase inhibitor therapy received serial measurements of serum estrone, estradiol, and DHEA-sulfate (DHEA-S). Steroid values during responsive and progressive phases of disease were compared. In vitro, human breast cancer cell lines T-47D (estrogen-receptor and progesterone-receptor positive) and HCC 1937 (estrogen-receptor and progesterone-receptor negative) were treated with DHEA-S. Proliferation rates were measured by colorimetric assay.
  
  
  RESULTS
  Disease in 12 of the 19 patients progressed. DHEA-S was less than 89 microg/dL in patients during the responsive phase and more than or equal to 89 microg/dL during disease progression, with 1 exception (P < .0005). Estrone and estradiol remained suppressed. After disease progression, the condition of 9 patients stabilized with aminoglutethimide therapy (n = 8) or adrenalectomy (n = 1), and their DHEA-S levels were reduced to less than 89 microg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells.
  
  
  CONCLUSIONS
  DHEA-S levels more than or equal to 89 microg/dL predicted disease progression in states of low estrogen. Tissue culture results supported the role of DHEA-S as an estrogenic agent. Oophorectomies with either aminoglutethimide therapy or adrenalectomy were effective remedies for breast cancer progression due to high DHEA-S.
authors.affiliation: Department of Surgery, Section of Surgical Oncology, Oregon Health Sciences University, Portland, OR 97201, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Toth-Fejel
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: W S
authors.initials: WS
authors.lastname: Fletcher
authors.forename: R F
authors.initials: RF
authors.lastname: Pommier
mesh_terms: D000315:Adrenalectomy; D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D014407:Tumor Cells, Cultured
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D000616:Aminoglutethimide; D019314:Dehydroepiandrosterone Sulfate