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Cancer Causes & Control

, Volume 22, Issue 4, pp 529–540 | Cite as

Estrogens in the breast tissue: a systematic review

  • Lusine YaghjyanEmail author
  • Graham A. Colditz
Review article

Abstract

The role of estrogens in breast carcinogenesis has been investigated at the level of whole body (plasma) and cell (molecular, receptors, etc.). Growing attention focused on the breast tissue being an intracrine organ, with potentially important local estrogen production in the breast. However, very little is known about the local breast tissue estrogen levels. Understanding the role of the tissue estrogens in breast carcinogenesis might open new avenues in breast cancer prevention. This systematic review summarizes published studies that measured local estrogen levels in the breast and offers suggestions for strategies to fill gaps in our existing scientific knowledge.

Keywords

Estrogen metabolites Tissue estrogen metabolism Breast carcinogenesis 

Abbreviations

BMI

Body mass index

CV

Coefficient of variation

LPAT

Laboratory of proteomics and analytical technologies

MS

Mass spectrometry

NCI

National Cancer Institute

Notes

Acknowledgments

Dr. Graham Colditz is supported by ACS Clinical Research Professorship.

Conflict of interests

The authors declare that they have no conflict of interests.

Supplementary material

10552_2011_9729_MOESM1_ESM.doc (109 kb)
Supplementary material 1 (DOC 109 kb)

References

  1. 1.
    Eliassen AH, Hankinson SE (2008) Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies. Adv Exp Med Biol 630:148–165PubMedCrossRefGoogle Scholar
  2. 2.
    Giese RW (2003) Measurement of endogenous estrogens: analytical challenges and recent advances. J Chromatogr A 1000(1–2):401–412PubMedCrossRefGoogle Scholar
  3. 3.
    Pattarozzi A, Gatti M, Barbieri F et al (2008) 17beta-estradiol promotes breast cancer cell proliferation-inducing stromal cell-derived factor-1-mediated epidermal growth factor receptor transactivation: reversal by gefitinib pretreatment. Mol Pharmacol 73(1):191–202PubMedCrossRefGoogle Scholar
  4. 4.
    LaMarca HL, Rosen JM (2007) Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage. Breast Cancer Res 9(4):304PubMedCrossRefGoogle Scholar
  5. 5.
    Russo J, Fernandez SV, Russo PA et al (2006) 17-Beta-estradiol induces transformation, tumorigenesis in human breast epithelial cells. FASEB J 20(10):1622–1634PubMedCrossRefGoogle Scholar
  6. 6.
    Seeger H, Deuringer FU, Wallwiener D, Mueck AO (2004) Breast cancer risk during HRT: influence of estradiol metabolites on breast cancer and endothelial cell proliferation. Maturitas 49(3):235–240PubMedCrossRefGoogle Scholar
  7. 7.
    Johansson CM, Anderson TJ, Bergstrom R, Lindgren A, Persson IR (1998) Epithelial proliferation in the normal human breast in relation to endogenous hormones and oral contraceptive use. Breast 7:162–167CrossRefGoogle Scholar
  8. 8.
    Sutherland RL, Prall OW, Watts CK, Musgrove EA (1998) Estrogen progestin regulation of cell cycle progression. J Mammary Gland Biol Neoplasia 3(1):63–72PubMedCrossRefGoogle Scholar
  9. 9.
    Foidart JM, Colin C, Denoo X et al (1998) Estradiol, progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril 69(5):963–969PubMedCrossRefGoogle Scholar
  10. 10.
    Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15(1):17–35PubMedGoogle Scholar
  11. 11.
    Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21(3):427–433PubMedCrossRefGoogle Scholar
  12. 12.
    Clemons M, Goss P (2001) Estrogen and the risk of breast cancer. N Engl J Med 344(4):276–285PubMedCrossRefGoogle Scholar
  13. 13.
    Rosner B, Colditz GA (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364PubMedCrossRefGoogle Scholar
  14. 14.
    Paffenbarger RS Jr, Kampert JB, Chang HG (1980) Characteristics that predict risk of breast cancer before, after the menopause. Am J Epidemiol 112(2):258–268PubMedGoogle Scholar
  15. 15.
    Zhu BT, Conney AH (1998) Functional role of estrogen metabolism in target cells: review, perspectives. Carcinogenesis 19(1):1–27PubMedCrossRefGoogle Scholar
  16. 16.
    Westerlind KC, Gibson KJ, Evans GL, Turner RT (2000) The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions. J Endocrinol 167(2):281–287PubMedCrossRefGoogle Scholar
  17. 17.
    Telang NT, Suto A, Wong GY, Osborne MP, Bradlow HL (1992) Induction by estrogen metabolite 16 alpha-hydroxyestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst 84(8):634–638PubMedCrossRefGoogle Scholar
  18. 18.
    McCormack VA, Dowsett M, Folkerd E et al (2009) Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women. Breast Cancer Res 11(3):R38PubMedCrossRefGoogle Scholar
  19. 19.
    Levina VV, Nolen B, Su Y et al (2009) Biological significance of prolactin in gynecologic cancers. Cancer Res 69(12):5226–5233PubMedCrossRefGoogle Scholar
  20. 20.
    Dabrosin C (2005) Positive correlation between estradiol and vascular endothelial growth factor but not fibroblast growth factor-2 in normal human breast tissue in vivo. Clin Cancer Res 11(22):8036–8041PubMedCrossRefGoogle Scholar
  21. 21.
    Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99(15):1178–1187PubMedCrossRefGoogle Scholar
  22. 22.
    Zhu BT (1998) Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 19:1–27PubMedCrossRefGoogle Scholar
  23. 23.
    Gruber CJ, Tschugguel W, Schneeberger C, Huber JC (2002) Production and actions of estrogens. N Engl J Med 346(5):340–352PubMedCrossRefGoogle Scholar
  24. 24.
    Sasano H, Miki Y, Nagasaki S, Suzuki T (2009) In situ estrogen production, its regulation in human breast carcinoma: from endocrinology to intracrinology. Pathol Int 59(11):777–789PubMedCrossRefGoogle Scholar
  25. 25.
    Sasano H, Nagasaki S, Miki Y, Suzuki T (2009) New developments in intracrinology of human breast cancer: estrogen sulfatase and sulfotransferase. Ann N Y Acad Sci 1155:76–79PubMedCrossRefGoogle Scholar
  26. 26.
    Recchione CVE, Manzari A, Cavalerri A, Martinetti A, Secreto G (1995) Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues. Steroid Biochem Molec Biol 52(6):541–546CrossRefGoogle Scholar
  27. 27.
    Pasqualini JR, Chetrite G, Blacker C et al (1996) Concentrations of estrone, estradiol, estrone sulfate, evaluation of sulfatase, aromatase activities in pre-and postmenopausal breast cancer patients. J Clin Endocrinol Metab 81(4):1460–1464PubMedCrossRefGoogle Scholar
  28. 28.
    Geisler J (2003) Breast cancer tissue estrogens and their manipulation with aromatase inhibitors and inactivators. J Steroid Biochem Mol Biol 86:245–253PubMedCrossRefGoogle Scholar
  29. 29.
    Labrie F, Luu-The V, Labrie C et al (2003) Endocrine, intracrine sources of androgens in women: inhibition of breast cancer, other roles of androgens, their precursor dehydroepiandrosterone. Endocr Rev 24(2):152–182PubMedCrossRefGoogle Scholar
  30. 30.
    Guillemette C, Belanger A, Lepine J (2004) Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Res 6(6):246–254PubMedCrossRefGoogle Scholar
  31. 31.
    Shatalova EG, Walther SE, Favorova OO, Rebbeck TR, Blanchard RL (2005) Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Breast Cancer Res 7(6):R909–R921PubMedCrossRefGoogle Scholar
  32. 32.
    Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72(1–2):23–27PubMedCrossRefGoogle Scholar
  33. 33.
    Riza E, dos Santos Silva I, De Stavola B et al (2001) Urinary estrogen metabolites, mammographic parenchymal patterns in postmenopausal women. Cancer Epidemiol Biomarkers Prev 10(6):627–634PubMedGoogle Scholar
  34. 34.
    Greendale GA, Palla SL, Ursin G et al (2005) The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol 162(9):826–834PubMedCrossRefGoogle Scholar
  35. 35.
    Tamimi RM, Hankinson SE, Colditz GA, Byrne C (2005) Endogenous sex hormone levels and mammographic density among postmenopausal women. Cancer Epidemiol Biomarkers Prev 14(11 Pt 1):2641–2647PubMedCrossRefGoogle Scholar
  36. 36.
    Bremnes Y, Ursin G, Bjurstam N et al (2007) Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women. Int J Cancer 121(11):2506–2511PubMedCrossRefGoogle Scholar
  37. 37.
    Johansson H, Gandini S, Bonanni B et al (2008) Relationships between circulating hormone levels, mammographic percent density, breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat 108(1):57–67PubMedCrossRefGoogle Scholar
  38. 38.
    Thomas H, Reeves G, Key T (1997) Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8(6):922–928PubMedCrossRefGoogle Scholar
  39. 39.
    Sheila Dawling DLH, Nady R, Fritz FP (2004) In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogens 2- and 4-hydroxyestradiol. Chem Res Toxicol 17:1258–1264PubMedCrossRefGoogle Scholar
  40. 40.
    Leane Lehmann JW (2008) Gene expression of 17b-estradiol-metabolizing isozymes: comparison of normal human mammary gland to normal human liver and to cultured human breast adenocarcinoma cells. Adv Exp Med Biol Hormonal Carcinogenesis V 617:617–624CrossRefGoogle Scholar
  41. 41.
    Rosselli MDR (2006) Estrogen metabolism and reproduction—is there a relationship? J für Fertilität und Reproduktion 16:19–23Google Scholar
  42. 42.
    Liehr JG (2001) Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development. Human Reproduction Update 2001 7(3):273–281Google Scholar
  43. 43.
    Westerlind KCGK, Evans GL, Turner RT (2000) The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions. J Endocrinol 167:281–287PubMedCrossRefGoogle Scholar
  44. 44.
    Telang NTSA, Wong GY, Osborne MP, Bradlow HL (1992) Induction by estrogen metabolite 16α-hydroxestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst 84:634–638PubMedCrossRefGoogle Scholar
  45. 45.
    Osborne MPBH, Wong GYC, Telang NT (1993) Upregulation of estradiol C16alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J Natl Cancer Inst 85:1917–1920PubMedCrossRefGoogle Scholar
  46. 46.
    Santen RJ, Santner SJ, Pauley RJ et al (1997) Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible? J Steroid Biochem Mol Biol 61(3–6):267–271PubMedCrossRefGoogle Scholar
  47. 47.
    Shekhar M, Pauley R, Heppner G (2003) Host microenvironment in breast cancer development: Extracellular matrix-stromal cell contribution to neoplastic phenotype of epithelial cells in the breast. Breast Cancer Res 5(3):130–135PubMedCrossRefGoogle Scholar
  48. 48.
    Reed MJ, Purohit A (1997) Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis. Endocr Rev 18(5):701–715PubMedCrossRefGoogle Scholar
  49. 49.
    Roy D, Cai Q, Felty Q, Narayan S (2007) Estrogen-induced generation of reactive oxygen, nitrogen species, gene damage, estrogen-dependent cancers. J Toxicol Environ Health B Crit Rev 10(4):235–257PubMedGoogle Scholar
  50. 50.
    Mueck AO, Seeger H (2007) Breast cancer: are oestrogen metabolites carcinogenic? Maturitas 57(1):42–46PubMedCrossRefGoogle Scholar
  51. 51.
    Li T, Sun L, Miller N et al (2005) The association of measured breast tissue characteristics with mammographic density, other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 14(2):343–349PubMedCrossRefGoogle Scholar
  52. 52.
    Ernster VL, Wrensch MR, Petrakis NL et al (1987) Benign, malignant breast disease: initial study results of serum, breast fluid analyses of endogenous estrogens. J Natl Cancer Inst 79(5):949–960PubMedGoogle Scholar
  53. 53.
    Recchione C, Venturelli E, Manzari A et al (1995) Testosterone, dihydrotestosterone, oestradiol levels in postmenopausal breast cancer tissues. J Steroid Biochem Mol Biol 52(6):541–546PubMedCrossRefGoogle Scholar
  54. 54.
    Vermeulen A, Deslypere JP, Paridaens R et al (1986) Aromatase, 17 beta-hydroxysteroid dehydrogenase, intratissular sex hormone concentrations in cancerous, normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 22(4):515–525PubMedCrossRefGoogle Scholar
  55. 55.
    van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH (1985) Endogenous concentration, subcellular distribution of estrogens in normal, malignant human breast tissue. Cancer Res 45(6):2900–2906PubMedGoogle Scholar
  56. 56.
    Beattie CW, Briele HA, Hart G, Das Gupta TK (1983) Estradiol and progesterone in human breast cancer cytosols and their relationship to receptor incidence. Cancer Invest 1(3):199–206PubMedCrossRefGoogle Scholar
  57. 57.
    Garvin S, Dabrosin C (2008) In vivo measurement of tumor estradiol and vascular endothelial growth factor in breast cancer patients. BMC Cancer 8:73PubMedCrossRefGoogle Scholar
  58. 58.
    O’Brien SN, Anandjiwala J, Price TM (1997) Differences in the estrogen content of breast adipose tissue in women by menopausal status, hormone use. Obstet Gynecol 90(2):244–248PubMedCrossRefGoogle Scholar
  59. 59.
    Blankenstein MA, Maitimu-Smeele I, Donker GH et al (1992) On the significance of in situ production of oestrogens in human breast cancer tissue. J Steroid Biochem Mol Biol 41(3–8):891–896PubMedCrossRefGoogle Scholar
  60. 60.
    Thijssen JH, Blankenstein MA, Donker GH, Daroszewski J (1991) Endogenous steroid hormones and local aromatase activity in the breast. J Steroid Biochem Mol Biol 39(5B):799–804PubMedCrossRefGoogle Scholar
  61. 61.
    Lonning PE, Helle H, Duong NK et al (2009) Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status. J Steroid Biochem Mol Biol 117(1–3):31–41PubMedCrossRefGoogle Scholar
  62. 62.
    Reed MJ, Aherne GW, Ghilchik MW, Patel S, Chakraborty J (1991) Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues. Int J Cancer 49(4):562–565PubMedCrossRefGoogle Scholar
  63. 63.
    Bonney RC, Reed MJ, Davidson K, Beranek PA, James VH (1983) The relationship between 17 beta-hydroxysteroid dehydrogenase activity, oestrogen concentrations in human breast tumours, in normal breast tissue. Clin Endocrinol (Oxf) 19(6):727–739CrossRefGoogle Scholar
  64. 64.
    Hankinson SE, Willett WC, Manson JE et al (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst 87(17):1297–1302PubMedCrossRefGoogle Scholar
  65. 65.
    Hankinson SE, Eliassen AH (2007) Endogenous estrogen, testosterone, progesterone levels in relation to breast cancer risk. J Steroid Biochem Mol Biol 106(1–5):24–30PubMedCrossRefGoogle Scholar
  66. 66.
    Missmer SA, Spiegelman D, Bertone-Johnson ER et al (2006) Reproducibility of plasma steroid hormones, prolactin, insulin-like growth factor levels among premenopausal women over a 2-to 3-year period. Cancer Epidemiol Biomarkers Prev 15(5):972–978PubMedCrossRefGoogle Scholar
  67. 67.
    Michaud DS, Manson JE, Spiegelman D et al (1999) Reproducibility of plasma, urinary sex hormone levels in premenopausal women over a one-year period. Cancer Epidemiol Biomarkers Prev 8(12):1059–1064PubMedGoogle Scholar
  68. 68.
    Thomas HV, Key TJ, Allen DS et al (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. Br J Cancer 75(7):1075–1079PubMedCrossRefGoogle Scholar
  69. 69.
    Boyapati SM, Shu XO, Gao YT et al (2004) Correlation of blood sex steroid hormones with body size, body fat distribution, other known risk factors for breast cancer in post-menopausal Chinese women. Cancer Causes Control 15(3):305–311PubMedCrossRefGoogle Scholar
  70. 70.
    Potischman N, Swanson CA, Siiteri P, Hoover RN (1996) Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 88(11):756–758PubMedCrossRefGoogle Scholar
  71. 71.
    Kopelman PG, Pilkington TR, White N, Jeffcoate SL (1980) Abnormal sex steroid secretion, binding in massively obese women. Clin Endocrinol (Oxf) 12(4):363–369CrossRefGoogle Scholar
  72. 72.
    Zumoff B (1982) Relationship of obesity to blood estrogens. Cancer Res 42(8 Suppl):3289s–3294sPubMedGoogle Scholar
  73. 73.
    De Pergola G, Giorgino F, Cospite MR et al (1993) Relation between sex hormones, serum lipoprotein, lipoprotein(a) concentrations in premenopausal obese women. Arterioscler Thromb 13(5):675–679PubMedGoogle Scholar
  74. 74.
    Grenman S, Ronnemaa T, Irjala K, Kaihola HL, Gronroos M (1986) Sex steroid, gonadotropin, cortisol, prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size, effect of weight reduction. J Clin Endocrinol Metab 63(6):1257–1261PubMedCrossRefGoogle Scholar
  75. 75.
    Van Beek AP, de Ruijter-Heijstek FC, Jansen H, Erkelens DW, de Bruin TW (2004) Sex steroids, plasma lipoprotein levels in healthy women: The importance of androgens in the estrogen-deficient state. Metabolism 53(2):187–192PubMedCrossRefGoogle Scholar
  76. 76.
    Caron P, Audet-Walsh E, Lepine J, Belanger A, Guillemette C (2009) Profiling endogenous serum estrogen and estrogen-glucuronides by liquid chromatography-tandem mass spectrometry. Anal Chem 81(24):10143–10148PubMedCrossRefGoogle Scholar
  77. 77.
    Blankenstein MA, van de Ven J, Maitimu-Smeele I et al (1999) Intratumoral levels of estrogens in breast cancer. J Steroid Biochem Mol Biol 69(1–6):293–297PubMedCrossRefGoogle Scholar
  78. 78.
    Chatterton RT Jr, Geiger AS, Khan SA et al (2004) Variation in estradiol, estradiol precursors, estrogen-related products in nipple aspirate fluid from normal premenopausal women. Cancer Epidemiol Biomarkers Prev 13(6):928–935PubMedGoogle Scholar
  79. 79.
    Dabrosin C (2005) Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle. J Endocrinol 187(1):103–108PubMedCrossRefGoogle Scholar
  80. 80.
    Yue W, Wang JP, Hamilton CJ, Demers LM, Santen RJ (1998) In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Res 58(5):927–932PubMedGoogle Scholar
  81. 81.
    Xu X, Veenstra TD, Fox SD et al (2005) Measuring fifteen endogenous estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry. Anal Chem 77(20):6646–6654PubMedCrossRefGoogle Scholar
  82. 82.
    Falk RT, Xu X, Keefer L, Veenstra TD, Ziegler RG (2008) A liquid chromatography-mass spectrometry method for the simultaneous measurement of 15 urinary estrogens, estrogen metabolites: assay reproducibility, interindividual variability. Cancer Epidemiol Biomarkers Prev 17(12):3411–3418PubMedCrossRefGoogle Scholar
  83. 83.
    Carlstrom K (1996) Low endogenous estrogen levels—analytical problems and tissue sensitivity. Acta Obstet Gynecol Scand Suppl 163:11–15PubMedGoogle Scholar
  84. 84.
    Nelson RE, Grebe SK, DJ OK, Singh RJ (2004) Liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of estradiol, estrone in human plasma. Clin Chem 50(2):373–384PubMedCrossRefGoogle Scholar
  85. 85.
    Bay K, Andersson AM, Skakkebaek NE (2004) Estradiol levels in prepubertal boys, girls–analytical challenges. Int J Androl 27(5):266–273PubMedCrossRefGoogle Scholar
  86. 86.
    Blonder J, Johann DJ, Veenstra TD et al (2008) Quantitation of steroid hormones in thin fresh frozen tissue sections. Anal Chem 80(22):8845–8852PubMedCrossRefGoogle Scholar
  87. 87.
    Xu X, Roman JM, Issaq HJ et al (2007) Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry. Anal Chem 79(20):7813–7821PubMedCrossRefGoogle Scholar
  88. 88.
    Xu X, Keefer LK, Ziegler RG, Veenstra TD (2007) A liquid chromatography-mass spectrometry method for the quantitative analysis of urinary endogenous estrogen metabolites. Nat Protoc 2(6):1350–1355PubMedCrossRefGoogle Scholar
  89. 89.
    Xu X, Othman Eel D, Issaq HJ et al (2008) Multiplexed quantitation of endogenous estrogens, estrogen metabolites in human peritoneal fluid. Electrophoresis 29(12):2706–2713PubMedCrossRefGoogle Scholar
  90. 90.
    Mady EA, Ramadan EE, Ossman AA (2000) Sex steroid hormones in serum and tissue of benign and malignant breast tumor patients. Dis Markers 16(3–4):151–157PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Division of Public Health Sciences, Department of SurgeryWashington University in St. Louis School of MedicineSt. LouisUSA
  2. 2.Institute for Public HealthWashington University in St. LouisSt. LouisUSA

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