Metabolismo de los estrógenos endógenos y cáncer de mama
Palabras clave:
CÁNCER DE MAMA, ESTRÓGENOS, DIETAResumen
El cáncer de mama es el cáncer más frecuente en las mujeres de los países desarrollados occidentales. Si bien Uruguay no integra este grupo de países, el cáncer de mama presenta cifras similares a estos, con tasas de incidencia y mortalidad extremadamente altas. La tasa de mortalidad ajustada por edad, en el período de 1993 a 1997, en Uruguay es de 25,1 cada 100.000 mujeres por año, una de las más altas a nivel mundial. Esto ha llevado a que el cáncer de mama sea un grave problema de salud pública en nuestro país.
La relación del cáncer de mama con el uso de hormonoterapia de reemplazo está firmemente establecida. Diversos estudios, en especial el estudio WHI (Women’s Health Initiative), han confirmado el mayor riesgo con el aporte exógeno de estrógenos. Esto, junto a los mayores riesgos cardiovasculares de la terapia estrogénica para los trastornos climatéricos, ha llevado a la drástica reducción de sus indicaciones y uso a nivel mundial.
Sin embargo, el rol de estas hormonas en la patogénesis del cáncer de mama no se reduce a su administración exógena. Los estrógenos endógenos tienen un papel preponderante en la génesis de este cáncer, y distintas situaciones dependientes del ambiente y los hábitos de vida pueden modificar el riesgo de cáncer de mama mediado por estrógenos endógenos. El presente artículo realiza una revisión sobre el metabolismo de los estrógenos y su relación con el cáncer de mama, dado que los distintos metabolitos de los estrógenos tienen acciones biológicas diferentes y una incidencia opuesta en el riesgo de este cáncer. La ruta de metabolización hacia la 2-alfa hydroxyestrona se asocia a una reducción de 40% de desarrollar cáncer de mama. Se analiza la influencia de los cambios dietéticos en la ruta de metabolización de los estrógenos y se plantea la hipótesis de aplicar el cambio de la dieta como una de las estrategias para abatir la incidencia del cáncer de mama.
Citas
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2) Ministerio de Salud Pública (Uruguay). División Estadística. Mortalidad clasificada por causa, sexo y edad. Montevideo. Montevideo: MSP, 1998.
3) De-Stéfani E, Fierro L, Barrios E, Ronco A. Cancer Mortality Trends in Uruguay, 1953-91. Int J Cancer 1994; 56(5): 634-9.
4) Writing Group for the Woman Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Woman. Principal results from the Women´s Health Initiative Randomized Controlled Trial. JAMA 2002; 288(3): 321-33.
5) Million Women Study Collborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003, 2(362): 419-27.
6) Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative re analysis of data from 51 epidemiological studies of 52.705 women with breast cancer and 108.411 women without breast cancer. Lancet 1997; 350(9084): 1047-59.
7) International Agency for Research on Cancer. Sex hormones (II). In: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. 1976 Vol 21. Lyon, France. Last updated: 6 April 1998. Obtenido de: http://monographs.iarc.fr/htdocs/indexes/vol21index.html. Fecha acceso: septiembre de 2004.
8) Clemons M, Goss P. Estrogen and the risk of breast cancer. N Engl J Med 2001; 344(23): 276-85.
9) Fuchs-Young R, Glasebrook AL, Short LL, Draper MW, Rippy MK, Cole HW, et al. Raloxifene is a tissue-selective agonist/antagonist that functions through the estrogen receptor. Ann N Y Acad Sci 1995; 761: 355-60.
10) Russo J, Lareef MH, Tahin Q, Hu YF, Slater C, Ao X, et al. 17 Beta-estradiol is carcinogenic in human breast epithelial cells. J Steroid Biochem Mol Biol 2002; 80(2): 149-62.
11) Liehr JG. Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development. Hum Reprod Update 2001; 7(3): 273-81.
12) Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994; 15: 342-55.
13) Dunn LJ, Bradbury JT. Endocrine factors in endometrial carcinoma: a preliminary report. Am J Obstet Gynecol 1967; 97: 465-71.
14) Ackerman GE, Smith ME, Mendelson CR, MacDonald PC, Simpson ER. Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 1981; 53: 412-7.
15) Simpson ER, Rubin G, Clyne C, Robertson K, O’Donnell, L, Jones M, et al. The role of local estrogen biosynthesis in males and females. Trends Endocrinol Metab 2000; 11: 184-8.
16) Bulun SE, Simpson ER, Word RA. Expression of the CYP19 gene and its product aromatase cytochrome P450 in human leiomyoma tissues and cells in culture. J Clin Endocrinol Metab 1994; 78: 736-43.
17) Noble LS, Simpson ER, Johns A, Bulun SE. Aromatase expression inendometriosis. J Clin Endocrinol Metab 1996; 81: 174-9.
18) Bulun SE, Price TM, Mahendroo MS, Aitken J, Simpson ER. A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab 1993; 77: 1622-8.
19) Yue W, Wang JP, Hamilton CJ, Demers LM, Santen RJ. In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Res 1998; 58: 927-32.
20) Haynes GJ, Dowsett AG, Lonning PE. Influence of letrozole (Femera) and anastrozole (Arimidex) on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized cross-over study. J Clin Oncol 2002; 20: 751-7.
21) Bajetta E, Zilembo N, Bichisao E, Martinetti A, Buzzoni R, Pozzi P, et al. Tumor response and estrogen suppression in breast cancer patients treated with aromatase inhibitors. Ann Oncol 2000; 11: 1017-22.
22) Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with petrozole and norethindrone acetate: a pilot study. Fertil Steril 2004; 81(2): 290-6.
23) Shozu M, Murakami K, Segawa T, Kasai T, Inoue M. Successful treatment of symptomatic uterine leiomyoma with a non-steroidal aromatase inhibitor in a perimenopausal woman. Fertil Steril 2003; 79: 628-31.
24) Ellis MJ, Jaenicke F, Llombart-Cussac L. A randomized double-blind multicentre study of preoperative tamoxifen versus Femara (letrozole) for postmenopausal women with ER and/or PgR positive breast cancer ineligible for breast conserving surgery -correlation of clinical response with tumour gene expression and proliferation. Breast Cancer Res Treat 2000; 64: 29.
25) Fishman J, Bradlow HL, Schneider J, Anderson KE, Kappas A. Radiometric analysis of biological oxidations in man: sex differences in estradiol metabolism. Proc Natl Acad Sci 1980; 77: 4957-60.
26) Fishman J, Osborne MP, Telang NT. The role of estrogen in mammary carcinogenesis. Ann NY Acad Sci 1995; 768: 91-100.
27) Hulka BS, Stark AT. Breast cancer: cause and prevention. Lancet 1995; 346(8979): 883-7.
28) Kreiger N, Sloan M, Cotterchis M, Kirch V. The risk of breast cancer following reproductive surgery. Eur J Cancer 1999; 35: 97-101.
29) Broocks A, Pirke KM, Schweiger U, Tuschl RJ, Laessle RG, Strowitzki T, et al. Cyclic ovarian function in recreational athletes. J Appl Physiol 1990; (68): 2083-6.
30) Bullen BA, Skrinar GS, Beitins IZ, Von Mering G, Turnbull BA, McArthur JW. Induction of menstrual disorders by strenuous exercise in untrained women. N Engl J Med 1985; 312(21): 1349-53.
31) Feicht CB, Johnson TS, Martin BJ, Sparkes KE, Wagner WJr. Secondary amenorrhea in athletes. Lancet 1978; 2(8100): 1145-6.
32) Bernstein L, Henderson BE, Hanisch R, Sullivan-Halley J, Ross RK. Physical exercise and reduced risk of breast cancer in young women. J Natl Cancer Inst 1994; 86(18): 1403-8.
33) Thune I, Brenn T, Lunde E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med 1997; 336(18): 1269-75.
34) Beatson G. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet 1896; 2: 104-7.
35) Thomas HV, Reeves GK, Key TJ. Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 1997; 8: 922-8.
36) Feigelson HS, Ross RK, Yu MC, Coetzee GA, Reichardt JK, Henderson BE. Genetic susceptibility to cancer from exogenous and endogenous exposures. J Cell Biochem Suppl 1996; 25: 15-22.
37) Sager R. Tumor-suppressor genes: The puzzle and the promise. Science 1989; 246(4936): 1406-12.
38) Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Hershmann K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266(5182): 66-71.
39) Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378(6559): 789-92.
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2005-03-31
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1.
Cóppola F, Nader J, Aguirre R. Metabolismo de los estrógenos endógenos y cáncer de mama. Rev. Méd. Urug. [Internet]. 31 de marzo de 2005 [citado 27 de julio de 2024];21(1):15-22. Disponible en: https://revista.rmu.org.uy/index.php/rmu/article/view/823
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