Mastopathie, Mammakarzinom und Jodlactone

Summary

An enlargement of the thyroid gland is often found in patients with breast cancer and fibrocystic disease. Experimental analysis in animals shows that iodine deficiency causes proliferations and dysplasia in the mammary gland similar to human fibrocystic disease. Elemental iodine supplementation can stop and partially lead to an involution of the mammary proliferations and dysplasia. Probably iodolactones are involved in the process of involution, similar to thyroid gland. The basis for iodolactone production in the mammary gland is given. Like the thyroid gland, the mammary gland can concentrate iodide by expressing the sodium/iodide symporter, the cell membrane transport protein. The sodium/iodide symporter is not only expressed during lactation but also in fibrocystic disease and in the majority of breast cancers. Iodolactones are synthesized with the mammary enzyme lactoperoxidase, an enzyme that is used for the pharmacological synthesis of iodolactones. Iodolactones can inhibit the EGF-receptor, thereby playing an important role in the pathophysiology of breast cancer and fibrocystic disease. Using the sodium/iodide symporter there are new options for the therapy of metastatic breast cancer.

Beitrag in Volltext: https://www.thieme-connect.de/ejournals/html/10.1055/s-2004-820575

Full text article: https://www.thieme-connect.de/ejournals/html/10.1055/s-2004-834453

Literatur

• 1 Adamopoulos D, Vassilaros S, Kapolla N, Papadiamatis J, Georgiakodis F, Michalakis A. Thyroid disease in patients with benign and malignant mastopathy.  Cancer. 1986;  57 125-128
• 2 Aquino T I, Eskin B A. Rat breast structure in altered iodine metabolism.  Arch Path. 1972;  94 280-285
• 3 Boccardo F, Marenghi C, Ghione G, Pepe A, Rubagotti A. Intracystic epidermal growth factor level is predictive of breast cancer risk in women with gross cystic disease of the breast.  Int J Cancer. 2001;  95 260-265
• 4 Denkert C, Winzer K J, Müller B M. et al . Elevated Expression of Cyclooxygenase-2 Is a Negative Prognostic Factor for Disease Free Survival and Overall Survival in Patients with Breast Carcinoma.  Cancer. 2003;  97 2978-2987
• 5 Druckmann R, Rohr U D. IGF-1 in gynaecology and obstetrics: update 2002.  Maturitas. 2002;  41 (Suppl 1) 65-83
• 6 Dugrillon A, Bechtner G, Uedelhoven W M, Weber P C, Gartner R. Evidence that an iodolactone mediates the inhibitory effect of iodide on thyroid cell proliferation but not on adenosine 3’, 5’-monophosphate formation.  Endocrinology. 1990;  127 337-343
• 7 Dugrillon A, Gärtner R. δ-Iodolactones decrease epidermal growth factor-induced proliferation and inositol-1,4,5-trisphosphate generation in porcine thyroid follicles - a possible mechanism of growth inhibition by iodide.  Eur J Endocrinol. 1995;  132 735-743
• 8 Dugrillon A, Gärtner R. The role of Iodine and Thyroid Cell Growth.  Thyroidology. 1992;  4 31-36
• 9 Dugrillon A, Uedelhoven W M, Pisarev M A, Bechtner G, Gartner R. Identification of delta-iodolactone in iodide treated human goiter and its inhibitory effect on proliferation of human thyroid follicles.  Horm Metab Res. 1994;  26 465-469
• 10 Eskin B A, Parker F J, Bassett J G, George D L. Human breast uptake of radioactive iodine.  Obstet Gynecol. 1974;  44 398-402
• 11 Eskin B A, Grotkowski C E, Connolly C P, Ghent W R. Different tissue responses for iodine and iodide in rat thyroid and mammary glands.  Biol Trace Elem Res. 1995;  49 9-19
• 12 Eskin B A, Shuman R, Krouse T, Merion J. Rat mammary gland atypia produced by iodine blockade with perchlorate.  Cancer Research. 1975;  35 2332-2339
• 13 Eskin B A. Iodine metabolism and breast cancer.  Trans Ny Acad Sci. 1970;  32 911-947
• 14 Funahashi H, Imai T, Mase T. et al . Seaweed prevents Breast cancer?.  Jpn J Cancer Res. 2001;  92 483-487
• 15 Funahashi H, Imai T, Tanaka Y. et al . Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat.  J Surgil Oncol. 1996;  61 209-213
• 16 Funahashi H, Imai T, Tanaka Y. et al . Wakeame seaweed supresses the proliferation of 7,12-Dimethylbenz(a)-anthracene-induced mammary tumors in rats.  Jpn J Cancer Res. 1999;  90 922-927
• 17 Gärtner R, Dugrillon A, Bechtner G. Evidence that iodolactones are the mediators of growth inhibition by iodine on the thyroid.  Acta Med Austriaca. 1996;  23 47-51
• 18 Gärtner R, Dugrillon A. Vom Jodmangel zur Struma.  Internist. 1998;  39 566-573
• 19 Ghent W R, Eskin B A, Low D A, Hill L P. Iodine replacement in fibrocystic disease of the breast.  Can J Surg. 1993;  36 453-460
• 20 Giani C, Fierabracci P, Bonacci R. et al . Relationship between breast cancer and thyroid disease: Relevance of autoimmune thyroid disorders in breast malignancy.  Clin Endocrinol Metab. 1996;  81 990-994
• 21 Hammami M M, Bakheet S. Radioiodine breast uptake in non-breastfeeding women: clinical and scintigraphic characteristics.  J Nucl Med. 1996;  37 26-31
• 22 Hill P, Wynder E L. Comparision of mammary adipose fatty acid composition in Japanese and American breast cancer patients.  Eur J Cancer Clin Oncol. 1987;  23 407-410
• 23 Kaizer L, Boyd N F, Kriukov V, Tritchler D. Fish consumption and breast cancer: An ecological study.  Nutr Cancer. 1989;  12 61-68
• 24 Klijn J GM, Berns P MJJ, Schmitz P IM, Foekens J A. The clinical significance of epidermal growth factor receptor ( EGF-R) in human breast cancer: A Review on 5232 patients.  Endocr Rev. 1992;  13 3-17
• 25 Kogai T, Schultz J J, Johnson L S, Huang M, Brent G A. Retinoic acid induces sodium-iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line.  Proc Natl Acad Sci USA. 2000;  97 8519-8524
• 26 Köhrle J. Der Natrium-Iodid-Symporter NIS: Funktion, Regulation und klinische Relevanz.  Z Ärztl Fortbild Qual Sich. 1999;  93 (Suppl 1) 17-22
• 27 Koifam S, Koifam R J. Breast cancer among Ashkenazi Jewish women in Sao Paulo and Porto Alegre, Brazil.  Breast Cancer Res. 2001;  3 270-275
• 28 Lichtenstein P, Holm V N, Verkasalo P K. et al . Enviromental and heritable factors in the Causation of cancer.  N Engl J Med. 2000;  343 78-85
• 29 Natarajan R, Esworthy R, Bai W, Gu J L, Wilczynski S, Nadler J. Increased 12-lipoxygenase expression in breast cancer tissues and cells: Regulation by epidermal growth factor.  J Clin Endocrinol Metab. 1997;  82 1790-1798
• 30 Natarjan R, Nadler J. Role of lipoxygenases in breast cancer.  Front Biosci. 1998;  3 E81-88
• 31 Nienhaus A, Hensel N, Roscher G. et al . Hormonelle, medizinische und lebensstilbedingte Faktoren und Brustkrebs.  Geburtsh Frauenheilk. 2002;  62 242-249
• 32 Normanno N, Ciardiello F. EGF-related peptides in the pathophysiology of the mammary gland.  J Mammary Gland Biol Neoplasia. 1997;  2 143-151
• 33 Pisani P, Parkin D M, Ferley J. Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden.  Int J Cancer. 1993;  55 891-903
• 34 Pisarev M A, Krawiec L, Juvenal G J. et al . Studies on the goiter inhibiting action of iodolactones.  Eur J Pharmacol. 1994;  158 33-37
• 35 Simon D, Koehrle J, Reiners C h. et al . Redifferentiation therapy with retinoids: Therapeutic option for advanced follicular and papillary thyroid carcinoma.  World J Surg. 1998;  22 569-574
• 36 Smyth P PA, Smith D F, McDermott E WM, Murray M J, Geraghty J G, O’Higgins N J. A direct relationship between thyroid enlargement and breast cancer.  J Clin Endocrinol Metab. 1996;  81 937-941
• 37 Spitzer E, Zschiesche W, Binas B, Grosse R, Erdmann B. EGF and TGF alpha modulate structural and functional differentiation of the mammary gland from pregnant mice in vitro: Possible role of the arachidonic acid pathway.  J Cell Biochem. 1995;  57 495-508
• 38 Spitzweg C, Harrington K J, Pinke L A, Vile R G, Morris J C. The sodium iodide symporter and its potential role in cancer therapy.  J Clin Endocrinol Metab. 2001;  86 3327-3335
• 39 Strum J M. Effect of iodine-deficiency on rat mammary gland.  Virchows Arch B Cell Pathol Incl Mol Pathol. 1979;  30 209-220
• 40 Tazebay U H, Wapnir I L, Levy O. et al . The mammary gland iodide transporter is expressed during lactation and in breast cancer.  Nat Med. 2000;  6 871-878
• 41 Turk J, Henderson W R, Klebanoff S J, Hubbard W C. Iodination of arachidonic acid mediated by eosinophil peroxidase, myeloperoxidase and lactoperoxidase.  Biochim Biophys Acta. 1983;  751 189-200