TY - JOUR
T1 - High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture
T2 - A renewed role for adrenalectomy
AU - Morris, Katherine T.
AU - Toth-Fejel, Su Ellen
AU - Schmidt, Joshua
AU - Fletcher, William S.
AU - Pommier, Rodney F.
N1 - Funding Information:
This research was supported by women's golf clubs in Oregon and the Oregon Chapter of the Order of the Eastern Star.
PY - 2001
Y1 - 2001
N2 - Bachground. 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 μg/dL in patients during the responsive phase and more than or equal to 89 μg/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 μg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells. Conclusions. DHEA-S levels more than or equal to 89 μg/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.
AB - Bachground. 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 μg/dL in patients during the responsive phase and more than or equal to 89 μg/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 μg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells. Conclusions. DHEA-S levels more than or equal to 89 μg/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.
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U2 - 10.1067/msy.2001.118378
DO - 10.1067/msy.2001.118378
M3 - Article
C2 - 11742322
AN - SCOPUS:0035666689
SN - 0039-6060
VL - 130
SP - 947
EP - 953
JO - Surgery (United States)
JF - Surgery (United States)
IS - 6
ER -