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Effects of raloxifene on normal breast tissue from premenopausal women

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Summary

The objective of this study was to evaluate the effects of raloxifene on normal breast tissue. A randomized, double-blind study was carried out in 30 ovulatory, premenopausal women of 18–40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into two groups: Group A (placebo, n=16) and Group B (raloxifene 60 mg, n=14). The medication was given for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day during which a sample of normal breast tissue was collected to evaluate the presence of the proliferating cell marker Ki-67. Student’s t-test was used for the statistical analysis of data (p<0.05). Mean percentage of stained nuclei in groups A and B was 10.96 ± 1.27 and 1.21 ± 0.26, respectively (p<0.001). Raloxifene significantly reduced the proliferative activity of normal breast tissue in premenopausal women.

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References

  1. Fisher B, Constantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux , Dimitrov N, Atkins J, Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 StudyJ Natl Cancer Inst 90(18):1371–1388, 1998

    Article  PubMed  CAS  Google Scholar 

  2. Osborne MP, Breast cancer prevention by antiestrogens Ann NY Acad Sci 889:146–151, 1999

    Article  PubMed  CAS  Google Scholar 

  3. Jordan VC, Progress in the prevention of breast cancer: concept to reality J Steroid Biochem Mol Biol 74(15):269–277, 2000

    Article  PubMed  CAS  Google Scholar 

  4. Cosman F, Selective estrogen-receptor modulators Clin Geriatr Med 19(2): 371–379, 2003

    Article  PubMed  Google Scholar 

  5. Gutman M, Couillard S, Roy J, Labrie F, Candes B, Labrie C, Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude mice Int J Cancer99(2):273–278, 2002

    Article  PubMed  CAS  Google Scholar 

  6. Stygar D, Muravitskaya N, Eriksson B, Eriksson H, Sahlin L, Effects of SERM (selective estrogen receptor modulator) treatment on growth and proliferation in the rat uterus Reprod Biol Endocrinol1(1): 40, 2003

    Article  PubMed  Google Scholar 

  7. Actis AM, Cocca CM, Gutierrez A, Croci M, Rivera ES, Bergoc RM, Estrogen receptor profiles: changes in mouse and rat mammary tumors by treatment with selective estrogens receptors modifiers Med Princ Pract 13(4): 220–226, 2004

    Article  PubMed  CAS  Google Scholar 

  8. Cummings SR, Eckert S, Krueger KA, Grady D, Powels TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC, The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiples outcomes of raloxifene evaluation JAMA 281(23):2189–2197, 1999

    Article  PubMed  CAS  Google Scholar 

  9. Cauley J, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, Farrerons J, Karasik A, Mellstrom D, Ng KW, Steppan JJ, Powles TJ, Morrow M, Costa A, Silfen Sl, Walls EL, Schmitt H, Muchmore D, Jordan VC, Ste Marie LG, Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4 year results from the MORE trial Breast Cancer Res Treat 67(2):191, 2001

    Article  CAS  Google Scholar 

  10. Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, Secrest RJ, Cummings SR, CORE Investigators Continuing outcomes relevant to evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene J Natl Cancer Inst 96(23):1751–1761, 2004

    Article  PubMed  CAS  Google Scholar 

  11. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, Boyle P, Overview of the main outcomes in breast-cancer prevention trials Lancet 361(9354):296–300, 2003

    Article  PubMed  CAS  Google Scholar 

  12. Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T, IBIS investigators First results from the International Breast Cancer Intervention Study (IBIS-I): a randomized prevention trial Lancet 360 (9336): 817–824, 2002

    Article  PubMed  CAS  Google Scholar 

  13. Vogel VG, Constantino JP, Wickerham DL, Cronin WM, Wolmark N, The study of tamoxifen and raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial Clin Breast Cancer 361(2): 153–159, 2002

    Article  Google Scholar 

  14. Vogel VG, Constantino JP, Wickerham DL, Cronin WM, National surgical adjuvant breast and bowel project update: prevention trials and endocrine therapy of ductal carcinoma in situ Clin Cancer Res 9(1Pt2): 4955–5015, 2003

    Google Scholar 

  15. Facina G, de Lima RG, Simões MJ, Novo NF, Gebrim LH, Estrogenic activity of tamoxifen on normal mammary parenchyma in the luteal phase of the menstrual cicle Int J Gynecol Obstet 569(1): 19–24, 1997

    Article  Google Scholar 

  16. de Lima GR, Facina G, Shida JY, Chein MB, Tanaka P, Dardes RC, Jordan VC, Gebrim LH, Effects of low doses tamoxifen on normal breast tissue from premenopausal women Eur J Cancer 39(7): 891–898, 2003

    Article  PubMed  CAS  Google Scholar 

  17. Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand HS, Validation studies for models projecting the risk of invasive and total breast cancer incidence J Natl Cancer Inst 91(18): 1541–1548. 1999

    Article  PubMed  CAS  Google Scholar 

  18. Bernardes JR Jr, Nonogaki S, Seixas MT, Rodrigues de Lima G, Baracat EC, Gebrim LH, Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue Int J Gynecol Obstet 67(1): 33–38, 1999

    Article  CAS  Google Scholar 

  19. de Sousa JA, Seixas MT, de Lima RG, Baracat EC, Gebrim LH, Evaluation of monoclonal antibody MIB-1in the mammary epithelium adjacent to fibroadenomas in premenopausal women treated with tamoxifen Breast J 7(6): 392–397, 2001

    Article  PubMed  Google Scholar 

  20. Wintzer HO, Zipfel I, Schulte-Monting J, Hellerich U, Von Kleist S, Ki67 immunostaining in human breast tumors and its relationship to prognosis Cancer 67(2): 421–428, 1991

    Article  PubMed  CAS  Google Scholar 

  21. Leers MPG, Theunissen PHMH, Ramaekers FCS, Schutte B, Multi-parameter flow cytometric analysis with detection of the Ki-67-Ag in paraffin embedded mammary carcinomas Cytometry 27(3): 283–289, 1997

    Article  PubMed  CAS  Google Scholar 

  22. Rudolph P, Peters J, Lorenz D, Schmidt D, Parwaresch R, Correlation between mitotic and Ki-67 labeling in paraffin-embedded carcinoma specimens Human Pathol 29(1): 1216–1222, 1998

    Article  CAS  Google Scholar 

  23. Dardes RDM, Horiguchi J, Jordan VC, A pilot study of the effects of short-term tamoxifen therapy on Ki-67 labeling index in women with primary breast cancer Int J Oncol 16(1): 25–30, 2000

    PubMed  CAS  Google Scholar 

  24. Nazário ACP, de Lima RG, Simões MJ, Novo NF, Cell Kinetics of the human mammary lobule during the proliferative and secretory phase of the menstrual cycle Bull Assoc Anat 79(244): 23–27, 1995

    Google Scholar 

  25. Jordan VC, Collins MM, Rowsby L, Prestwich GA, Monohydroxylated metabolite of tamoxifen with potent antiestrogenic activity J Endocrinol 75(2): 305–316, 1977

    PubMed  CAS  Google Scholar 

  26. Black LJ, Jones CD, Falcone JF, Antagonism of estrogen action with a new benzothiophene derived antiestrogen Life Sci 32(9): 1031–1036, 1983

    Article  PubMed  CAS  Google Scholar 

  27. MacGregor SJ, Liu H, Bretrem DJ, Zapf JW, Jordan VC, Allosteric silencing of activating function 1 in the hydroxytamoxifen estrogen receptor complex is induced by substituting glycine for aspartate at amino acid 351 Cancer Res 60(18): 5097–6105, 2000

    PubMed  Google Scholar 

  28. Liu H, Park WC, Bentrem DJ, McKian KP, Reyes Ade L, Loweth JA, Schafer JM, Zapf JW, Jordan VC, Structure-function relationships of the raloxifene-estrogen receptor-alpha complex for regulating transforming growth factor-alpha expression in breast cancer cells J Biol Chem 277(11): 9189–9198, 2002

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Benedito Borges da Silva.

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Address for offprints and correspondence to: Benedito Borges da Silva, Avenida Elias João Tajra, 1600, Apt. 600, Edifício Oscar Niemeyer, Jockey Club, 64.049-300 Teresina, Piauí, Brazil; Tel./Fax: +55-86+215-0470; E-mail: beneditoborges@globo.com

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da Silva, B.B., Lopes, I.M.R.S. & Gebrim, L.H. Effects of raloxifene on normal breast tissue from premenopausal women. Breast Cancer Res Treat 95, 99–103 (2006). https://doi.org/10.1007/s10549-005-9001-2

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  • DOI: https://doi.org/10.1007/s10549-005-9001-2

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