Hanna Savolainen-Peltonen1, Veera Vihma, Marjut Leidenius, Feng Wang, Ursula Turpeinen, Esa Hämäläinen, Matti J Tikkanen, Tomi S Mikkola. 1. Department of Obstetrics and Gynecology (H.S.-P., T.S.M.) and Heart and Lung Center (V.V., F.W., M.J.T.), Helsinki University Central Hospital and University of Helsinki, Folkhälsan Research Center (H.S.-P., V.V., F.W., M.J.T., T.S.M.), Biomedicum, and Breast Surgery Unit (M.L.) and HUSLAB (U.T., E.H.), Helsinki University Central Hospital, 00029 Helsinki, Finland.
Abstract
CONTEXT: It has been shown that breast tumor actively produces and metabolizes steroid hormones. However, little is known about the possible mechanisms through which the nonmalignant adipose tissue contributes to steroid hormone metabolism. OBJECTIVE: We compared the metabolic pathways producing active estradiol in breast sc adipose tissue of postmenopausal women with or without breast cancer. DESIGN AND SETTING: Serum and adipose tissue samples were obtained during elective surgery. PATIENTS: We studied postmenopausal women undergoing mastectomy due to an estrogen receptor-positive breast tumor (n = 14) and women undergoing breast reduction mammoplasty (n = 14). INTERVENTIONS: Estrone, estradiol, and estradiol fatty acyl ester concentrations were determined by liquid chromatography-tandem mass spectrometry. mRNA expression levels of estrogen-converting enzymes were analyzed by quantitative RT-PCR. RESULTS: Estradiol concentration in breast sc adipose tissue was lower in women with cancer than in controls (median 33 vs 62 pmol/kg; P = .002), whereas the serum concentrations did not differ. Also, the mRNA expression for 17β-hydroxysteroid dehydrogenase type 12 was lower in the adipose tissue of women with cancer compared with controls (0.19 ± 0.10 vs 0.37 ± 0.21, P = .018). CONCLUSIONS: Estrogen metabolism is differentially regulated in the adipose tissue of women with or without cancer. In the sc adipose tissue proximal to breast tumor 17β-hydroxysteroid dehydrogenase type 12 expression is lower than in controls, which could indicate that the conversion of estrone to estradiol is decreased. Further studies are needed to establish the clinical significance of our findings in the development and growth of breast cancer in postmenopausal women.
CONTEXT: It has been shown that breast tumor actively produces and metabolizes steroid hormones. However, little is known about the possible mechanisms through which the nonmalignant adipose tissue contributes to steroid hormone metabolism. OBJECTIVE: We compared the metabolic pathways producing active estradiol in breast sc adipose tissue of postmenopausal women with or without breast cancer. DESIGN AND SETTING: Serum and adipose tissue samples were obtained during elective surgery. PATIENTS: We studied postmenopausal women undergoing mastectomy due to an estrogen receptor-positive breast tumor (n = 14) and women undergoing breast reduction mammoplasty (n = 14). INTERVENTIONS:Estrone, estradiol, and estradiol fatty acyl ester concentrations were determined by liquid chromatography-tandem mass spectrometry. mRNA expression levels of estrogen-converting enzymes were analyzed by quantitative RT-PCR. RESULTS:Estradiol concentration in breast sc adipose tissue was lower in women with cancer than in controls (median 33 vs 62 pmol/kg; P = .002), whereas the serum concentrations did not differ. Also, the mRNA expression for 17β-hydroxysteroid dehydrogenase type 12 was lower in the adipose tissue of women with cancer compared with controls (0.19 ± 0.10 vs 0.37 ± 0.21, P = .018). CONCLUSIONS: Estrogen metabolism is differentially regulated in the adipose tissue of women with or without cancer. In the sc adipose tissue proximal to breast tumor 17β-hydroxysteroid dehydrogenase type 12 expression is lower than in controls, which could indicate that the conversion of estrone to estradiol is decreased. Further studies are needed to establish the clinical significance of our findings in the development and growth of breast cancer in postmenopausal women.
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