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Role of Retinoid Receptors in the Prevention and Treatment of Breast Cancer

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Abstract

Retinoids are vitamin A-related compounds thathave been found to prevent cancer in animals and humans.In this review, we discuss the role of retinoids andtheir receptors in the treatment and prevention of breast cancer. The retinoid receptors areexpressed in normal and malignant breast cells, and arecritical for normal development. In breast cells, whenbound by retinoid hormones, these proteins regulate proliferation, apoptosis, and differentiation.The mechanism by which retinoids inhibit breast cellgrowth has not been completely elucidated, however,retinoids have been shown to affect multiple signal transduction pathways, including IGF-,TGFβ-, and AP-1-dependent pathways. Retinoids havealso been shown to suppress the growth and prevent thedevelopment of breast cancer in animals. These agents suppress tumorigenesis in carcinogen-treatedrats and in transgenic mice, and inhibit the growth oftransplanted breast tumors. These promising preclinicalresults have provided the rationale to test retinoids in clinical trials for the treatment andprevention of breast cancer. Several retinoids,including all trans retinoic acid and9-cis retinoic acid, have been shown to havemodest activity in the treatment of breast cancer, and theseagents are now in clinical trials in combination withcytotoxic agents and anti-estrogens. Another retinoid,4-HPR, is currently being tested in a human cancer prevention trial. Preliminary results suggestthat 4-HPR may suppress breast cancer development inpremenopausal women. Future clinical trials will focuson testing new synthetic retinoids that have reduced toxicity and enhanced therapeutic andpreventive efficacy.

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REFERENCES

  1. R. C. Moon, R. G. Mehta, and K. V. N. Rao (1994). Retinoids and cancer in experimental animals. In M. B. Sporn, A. B. Roberts, and D. S. Goodman (eds.), The Retinoids: Biology, Chemistry, and Medicine, Second Edition, Raven Press, New York, pp. 573–595.

    Google Scholar 

  2. M. E. Huang, Y. C. Ye, S. R. Chen, J. R. Chai, J. X. Lu, L. Zhao, L. J. Gu, and Z. Y. Wang (1988). Use of all-trans-retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72:567.

    PubMed  Google Scholar 

  3. W. K. Hong, S. M. Lippman, L. M. Itri, D. D. Karp, J. S. Lee, R. M. Byers, S. P. Schantz, A. M. Kramer, R. Lotan, L. J. Peters, I. W. Dimery, B. W. Brown, and H. Goepfert (1990). Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 323:795–801.

    PubMed  Google Scholar 

  4. D. J. Mangelsdorf, K. Umesono, and R. Evans (1994). The retinoid receptors. In M. B. Sporn, A. B. Roberts, and D. S. Goodman (eds.), The Retinoids: Biology, Chemistry, and Medicine, Second Edition, Raven Press, New York, pp. 319–349.

    Google Scholar 

  5. T. Perlmann and R. M. Evans (1997). Nuclear receptors in sicily: All in the famiglia. Cell 90:391–397.

    PubMed  Google Scholar 

  6. R. J. Lin, L. Nagy, S. Inoue, W. Shao, W. H. Miller, Jr., and R. Evans (1998). Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 391:811–818.

    PubMed  Google Scholar 

  7. S.-H. Hong, G. David, C.-W. Wong, A. Dejean, and M. L. Privalsky (1997). SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor α (RARα) and PLZF-RARα oncoproteins associated with acute promyelocytic leukemia. Proc. Natl. Acad. Sci. U.S.A. 94:9028–9033.

    PubMed  Google Scholar 

  8. M. A. Pignatello, F. C. Kauffman, and A. A. Levin (1997). Multiple factors contribute to the toxicity of the aromatic retinoid, TTNPB (Ro 13–7410): Binding affinities and disposition. Toxicol Appl. Pharmacol. 142:319–327.

    PubMed  Google Scholar 

  9. S. Toma, L. Isnaardi, L. Riccardi, and W. Bollag (1998). Induction of apoptosis in MCF-7 breast carcinoma cell line by RAR and RXR selective retinoids. Anticancer Res. 18:935–942.

    PubMed  Google Scholar 

  10. D. R. Shalinsky, E. D. Bischoff, W. W. Lamph, L. Zhang, M. F. Boehm, P. J. A. Davies, A. M. Nadzan, and R. A. Heyman (1997). A novel retinoic acid receptor-selective retinoid, ALRT1550, has potent antitumor activity against human oral squamous carcinoma xenografts in nude mice. Cancer Res. 57:162–168.

    PubMed  Google Scholar 

  11. J. Y. Chen, S. Penco, J. Ostrowski, P. Balague, M. Pon, J. Starrett, P. Reczek, P. Chambon, and H. Gronemeyer (1995). RAR-specific agonist/antagonists which dissociate transactivation and AP1 transrepression inhibit anchorage-independent cell proliferation. EMBO J. 14:1187–1197.

    PubMed  Google Scholar 

  12. S. Toma, L. Isnardi, P. Raffo, L. Riccaardi, G. Dastoli, C. Apfel, P. LeMotte, and W. Bollag (1998). RARα antagonist RO 41–5253 inhibits proliferation and induces apoptosis in breast cancer cell lines. Int. J. Cancer 78:86–94.

    PubMed  Google Scholar 

  13. M. S. Sheikh, Z.-M. Shao, Z.-S. Li, J. V. Ordonez, B. A. Conley, S. Wu, M. I. Dawson, Q.-X. Han, W.-R. Chao, T. Quick, R. M. Niles, and J. A. Fontana (1995). N-(4–hydroxyphenyl)retinamide (4–HPR)-mediated biological actions involve retinoid receptor-independent nt pathways in human breast carcinoma. Carcinogenesis 16:2477–2486.

    PubMed  Google Scholar 

  14. P. Kastner, M. Mark, and P. Chambon (1995). Nonsteroid nuclear receptors: What are genetic studies telling us about their role in real life? Cell 83:859–869.

    PubMed  Google Scholar 

  15. P. Kastner, J. M. Grondona, M. Mark, A. Gansmuller, M. LeMeur, D. Decimo, J.-L. Vonesch, P. Dolle, and P. Chambon (1994). Genetic analysis of RXRα developmental function: Concergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell 78:987–1003.

    PubMed  Google Scholar 

  16. V. Sapin, P. Dolle, C. Hindelang, P. Kastner, and P. Chambon (1997). Defects of the chorioallantoic placenta in mouse RXRα null fetuses. Dev. Biol. 191:29–41.

    PubMed  Google Scholar 

  17. T. Manshouri, Y. Yang, H. Lin, S. A. Stass, A. B. Glassman, and M. J. Keating (1997). Downregulation of RARα in mice by antisense transgene leads to a compensatory increase in RARβ and RARγ and development of lymphoma. Blood 89:2507–2515.

    PubMed  Google Scholar 

  18. P. Kastner, M. Mark, M. Leid, A. Gansmuller, J. M. Grondona, D. Decimo, W. Krezel, B. Chin, A. Dierich, and P. Chambon (1996). Abnormal spermatogenesis in RXRβ mutant mice. Genes Dev. 10:80–92.

    PubMed  Google Scholar 

  19. W. Krezel, V. Dupe, M. Mark, A. Dierich, P. Kastner, and P. Chambon (1996). RXRγ null mice are apparently normal and compound RXRα+/−/RXRβ−/−/RXRγ−/− mutant mice are viable. Proc. Natl. Acad. Sci. USA 93:9010–9014.

    PubMed  Google Scholar 

  20. R. C. Moon, R. G. Mehta, and D. L. McCormick (1985). Retinoids and mammary gland differentiation. In Retinoids, Differentiation and Disease, Pittman, London, pp. 156–167.

    Google Scholar 

  21. L. J. Gudas (1992). Retinoids, retinoid-response genes, cell differentiation and cancer. Cell Growth Differ. 3:655–662.

    PubMed  Google Scholar 

  22. S. D. Roman, C. L. Clarke, R. E. Hall, I. E. Alexander, and R. L. Sutherland (1992). Expression and regulation of retinoic acid receptors in human breast cancer cells. Cancer Res. 52:2236–2242.

    PubMed  Google Scholar 

  23. K. Swisshelm, K. Ryan, X. Lee, H. C. Tsou, M. Peacock, and R. Sager (1994). Down-regulation of retinoic acid receptor β in mammary carcinoma cell lines and its up-regulation in senescing normal mammary epithelial cells. Cell Growth Differ. 5:133–141.

    PubMed  Google Scholar 

  24. X.-C. Xu, N. Sneige, X. Liu, R. Nandagiri, J. J. Lee, F. Lukmanji, G. Hortobagyi, S. M. Lippman, K. Dhingra, and R. Lotan (1997). Progressive decrease in nuclear retinoic acid receptor β messenger RNA level during breast carcinogenesis. Cancer Res. 57:4992–4996.

    PubMed  Google Scholar 

  25. B. van der Burg, B. M. van der Leede, L. Kwakkenbos-Isbrucker, S. Salverda, S. W. de Laat, and P. T. van der Saag (1993). Retinoic acid resistance of estradiol-independent breast cancer cells coincides with diminished retinoic acid receptor function. Mol. Cell Endocrinol. 91:149–157.

    PubMed  Google Scholar 

  26. P. Fitzgerald, M. Teng, R. A. S. Chandraratna, R. A. Heyman, and E. A. Allegretto (1997). Retinoic acid receptor α expression correlates with retinoid-induced growth inhibition of human breast cancer cells regardless of estrogen receptor status. Cancer Res. 57:2642–2650.

    PubMed  Google Scholar 

  27. M. S. Sheikh, Z.-M. Shao, X.-S. Li, M. Dawson, A. M. Jetten, S. Wu, B. A. Conley, M. Garcia, H. Rochefor, and J. A. Fontana (1994). Retinoid-resistant estrogen receptor-negative human breast carcinoma cells transfected with retinoic acid receptor-α acquire sensitivity to growth inhibition by retinoids. J. Biol. Chem. 269:21440–21447.

    PubMed  Google Scholar 

  28. T. K. Chen, L. M. Smith, D. K. Gebhardt, M. J. Birrer, and P. H. Brown (1996). Activation and inhibition of the AP1 complex in human breast cancer cells. Mol. Carcinogenesis 15:215–226.

    Google Scholar 

  29. L. M. Smith, M. J. Birrer, M. R. Stampfer, and P. H. Brown (1997). Breast cancer cells have lower mammalian activating protein 1 transcription factor activity than normal mammary epithelial cells. Cancer Res. 57:3046–3054.

    PubMed  Google Scholar 

  30. M. Pfahl (1993). Nuclear receptor/AP-1 interaction. Endocrine Rev. 14:651–658.

    Google Scholar 

  31. L. Yang, H.-T. Kim, D. Munoz-Medellin, P. Reddy, and P. H. Brown (1997). Induction of retinoid resistance in breast cancer cells by overexpression of cJun. Cancer Res. 57:4652–4661.

    PubMed  Google Scholar 

  32. S. Kojima and D. B. Rifkin (1993). Mechanism of retinoid-induced activation of latent transforming growth factor-β in bovine endothelial cells. J. Cell Physiol. 155:323–332.

    PubMed  Google Scholar 

  33. J. Nunes, S. Kojima, and D. B. Rifkin (1996). Effect of endogenously activated transforming growth factor-β on growth and differentiation of retinoic acid-treated HL-60 cells. Cancer Res. 56:495–499.

    PubMed  Google Scholar 

  34. K. M. Eck, L. Yuan, L. Duffy, and P. T. Ram (1998). A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumor cells. Brit. J. Cancer 77:2129–2137.

    PubMed  Google Scholar 

  35. J. M. Turley, L. A. Falk, F. W. Ruscetti, J. J. Kasper, T. Francomano, T. Fu, O. S. Bang, and M. C. Birchenall-Roberts (1996). Transforming growth factor β1 functions in monocytic differentiation of hematopoietic cells through autocrine and paracrine mechanisms. Cell Growth Differ. 7:1535–1544.

    PubMed  Google Scholar 

  36. M. Hosobuchi and M. R. Stampfer (1989). Effects of transforming growth factor β-on growth of human mammary epithelial cells in culture. In Vitro Cell Dev. Biol. 25:705–713.

    PubMed  Google Scholar 

  37. V. L. Seewaldt, J.-H. Kim, L. E. Caldwell, B. S. Johnson, K. Swisshem, and S. J. Collins (1997). All-trans-retinoic acid mediates G1 arrest but not apoptosis of normal human mammary epithelial cells. Cell Growth Differ. 8:631–641.

    PubMed  Google Scholar 

  38. J. L. Martin, J. A. Coverley, S. T. Pattison, and R. C. Baxter (1995). Insulin-like growth factor binding protein-3 production by MCF-7 breast cancer cells: Stimulation by retinoic acid and cyclic adenosine monophosphate and differential effects of estradiol. Endocrinology 136:1219–1226.

    PubMed  Google Scholar 

  39. Y. Oh, Z. Gucev, L. Ng, H. L. Muller, and R. G. Rosenfeld (1995). Antiproliferaative actions of insulin-like growth factor binding protein (IGFBP-3) in human breast cancer cells. Prog. Growth Factor Res. 6:503–512.

    PubMed  Google Scholar 

  40. Z. S. Gucev, T. Y. O, K. M. Kelly, and R. G. Rosenfeld (1996). Insulin-like growth factor binding protein 3 mediates retinoic acid-and transforming growth factor β2–induced growth inhibition in human breast cancer cells. Cancer Res. 56:1545–1550.

    PubMed  Google Scholar 

  41. V. L. Seewaldt, B. S. Johnson, M. B. Parker, S. J. Collins, and K. Swisshelm (1995). Expression of retinoic acid receptor β mediates retinoic acid-induced growth arrest and apoptosis in breast cancer cells. Cell Growth Differ. 6:1077–1088.

    PubMed  Google Scholar 

  42. H. DeThe, M. del Mar Vivanco-Ruiz, P. Tiollais, H. Stunnenberg, and A. Dejean (1990). Identification of a retinoic acid responsive element in the retinoic acid receptor-β gene. Nature 343:177–180.

    PubMed  Google Scholar 

  43. X.-S. Li, Z.-M. Shao, M. S. Sheikh, J. L. Eiseman, D. Sentz, A. M. Jetten, J.-C. Chen, M. I. Dawson, S. Aisner, A. K. Rishi, P. Gutierrez, L. Schnapper, and J. A. Fontana (1995). Retinoic acid nuclear receptor β inhibits breast carcinoma anchorage independent growth. J. Cell. Physiol. 165:449–458.

    PubMed  Google Scholar 

  44. Q. Zhou, M. Stetler-Stevenson, and P. S. Steeg (1997). Inhibitions of cyclin D expression in human breast carcinoma cells by retinoids in vitro. Oncogene 15:107–115.

    PubMed  Google Scholar 

  45. S. Toma, L. Isnardi, P. Raffo, G. Dastoli, E. DeFrancisci, L. Riccardi, R. Palumbo, and W. Bollag (1997). Effects of all-trans-retinoic acid and 13–cis-retinoic acid on breast cancer cell lines: Growth inhibition and apoptosis induction. Int. J. Cancer 70:619–627.

    PubMed  Google Scholar 

  46. A. N. Fanjul, F. J. Piedrafita, H. Al-Shamma, and M. Pfahl (1998). Apoptosis induction and potent antiestrogen receptor-negative breast cancer activity in vivo by a retinoid antagonist. Cancer Res. 58:4607–4610.

    PubMed  Google Scholar 

  47. Y. Jing, J. Zhang, S. Waxman, and R. Mira-y-Lopez (1996). Upregulation of cytokeratins 8 and 18 in human breast cancer T47D cells is retinoid-specific and retinoic acid receptor-dependent. Differentiation 60:109–117.

    PubMed  Google Scholar 

  48. P. T. Lee, M. T. Lee, K. M. Darcy, K. Shudo, and M. M. Ip (1995). Modulation of normal mammary epithelial cell proliferation, morphogenesis, and functional differentiation by retinoids: A comparison of the retinobenzoic acid derivative RE80 with retinoic acid. Endocrinology 136: 1707–1717.

    PubMed  Google Scholar 

  49. Y. S. Lopez-Boado, J. Tolivia, and C. Lopez-Otin (1994). Apolipoprotein D gene induction by retinoic acid is concomitant with growth arrest and cell differentiation in human breast cancer cells. J. Biol. Chem. 269:26871–26878.

    PubMed  Google Scholar 

  50. S. S. Bacus, K. Kiguchi, D. Chin, C. R. King, and E. Huberman (1990). Differentiation of cultured human breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen. Mol. Carcinogenesis 3:350–362.

    Google Scholar 

  51. R. Clarke (1996). Animal models of breast cancer. In J. R. Hariss, M. E. Lippman, M. Morrow, and S. Hellman (eds.), Diseases of the Breast, Lippincott-Raven, pp. 235–244.

  52. R. Clarke (1997). Animal models of breast cancer: Experimental design and their use in nutritin and psychosocial research. Breast Cancer Res. Treat. 46:117–133.

    PubMed  Google Scholar 

  53. C.J. Grubbs et al. (1991). Effect of canthaxanthin on chemically induced mammary carcinogenesis. Oncology 48:239–245.

    PubMed  Google Scholar 

  54. R. C. Moon, H. J. Thompson, P. J. Becci, C. J. Grubbs, R. J. Gander, D. L. Newton, J. M. Smith, S. L. Phillips, W. R. Henderson, L. T. Mullen, C. C. Brown, and M. B. Sporn (1979). N-(4–hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res. 39:1339–1346.

    PubMed  Google Scholar 

  55. H. Abou-Issa, T. E. Webb, J. P. Minton, and M. Moeschberger (1989). Chemotherapeutic evaluation of glucarate and N-(4–hydroxyphenyl)retinamide alone and in combination in the rat mammary tumor model. J. Natl. Cancer. Inst. 81:1820–1823.

    PubMed  Google Scholar 

  56. C. J. Grubbs, I. Eto, M. M. Juliana, J. M. Hardin, and L. M. Whitaker (1990). Effects of retinyl acetate and 4–hydroxyphenylretinamide on initiation of chemically-induced mammary tumors. Anticancer Res. 10:661–666.

    PubMed  Google Scholar 

  57. R. C. Moon, D. L. McCormick, and R. G. Methta (1983). Inhibition of carcinogenesis by retinoids. Cancer Res. 43:2469–2475s.

    Google Scholar 

  58. M. A. Anzano, S. W. Byers, J. M. Smith, C. W. Peer, L. T. Mullen, C. C. Brown, A. B. Roberts, and M. B. Sporn (1994). Prevention of breast cancer in the rat with 9–cis-retinoic acid as a single agent and in combination with tamoxifen. Cancer Res. 54:4614–4617.

    PubMed  Google Scholar 

  59. M. A. Anzano, C. W. Peer, J. M. Smith, L. T. Mullen, M. W. Shrader, D. L. Logsdon, C. L. Driver, C. C. Brown, A. B. Roberts, and M. B. Sporn (1996). Chemoprevention of mammary carcinogenesis in the rat: Combined use of raloxifene and 9–cis-retinoic acid. J. Natl. Cancer Instit. 88:123.

    Google Scholar 

  60. M. M. Gottardis, E. D. Bischoff, M. A. Shirley, M. A. Wagoner, W. W. Lamph, and R. A. Heyman (1996). Chemoprevention of mammary carcinoma by LGD1069 (Targretin): An RXR-selective ligand. Cancer Res. 56:5566–5570.

    PubMed  Google Scholar 

  61. E. D. Bischoff, M. M. Gottardis, T. E. Moon, R. A. Heyman, and W. W. Lamph (1998). Beyond tamoxifen: The retinoid X receptor-selective ligand LGD1069 (TARGRETIN) causes complete regression of mammary carcinoma. Cancer Res. 58:479–484.

    PubMed  Google Scholar 

  62. E. Elstner, C. Muller, K. Koshizuka, E. A. Williamson, D. Park, H. Asou, P. Shintaku, J. W. Said, D. Heber, and H. P. Koeffler (1998). Ligands for peroxisome proliferaor-activated receptor γ and retinoic acid receptor inhibit growth and induce apaptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. U.S.A. 95:8806–8811.

    PubMed  Google Scholar 

  63. B. A. Conley, T. S. Ramsland, D. L. Sentz, S. Wu, D. M. Rosen, M. Wollman, and J. L. Eiseman (1999). Antitumor activity, distribution, and metabolism of 13–cis-retinoic acid as a single agent or in combination with tamoxifen in established human MCF-7 xenografts in mice. Cancer Chemother. Pharmacol. 43:183–197.

    PubMed  Google Scholar 

  64. L. D. Fraker, S. A. Halter, and J. T. Forbes (1984). Growth inhibition by retinol of a human breast carcinoma cell line in vitro and in athymic mice. Cancer Res. 44:5757–5763.

    PubMed  Google Scholar 

  65. S. A. Halter, L. D. Fraker, D. Adcock, and S. Vick (1988). Effect of retinoids on xenotransplanted human mammary carcinoma cells in athymic mice. Cancer Res. 48:3733–3736.

    PubMed  Google Scholar 

  66. R. R. Mehta, M. E. Hawthorne, J. M. Graves, and R. G. Mehta (1998). Metabolism of N-[4–hydroxyphenyl]retinamide (4–HPR) to N-[4–methoxyphenyl]retinamide (4–MPR) may serve as a biomarker for its efficacy against human breast cancer and melanoma cells. Eur. J. Cancer 34:902–907.

    PubMed  Google Scholar 

  67. C. Watson, D. Medina, and J. H. Clark (1977). Estrogen receptor characterization in transplantable mouse mammary tumor. Cancer Res. 37:3344–3348.

    PubMed  Google Scholar 

  68. F. Darro, P. Cahen, A. Vianna, C. Decaestecker, J. M. Nogaret, B. Leblond et al. (1998). Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 antiprogestagen. Breast Cancer Res. Treat. 51:39–55.

    PubMed  Google Scholar 

  69. G. N. Rao, E. Ney, and R. A. Herbert (1998). Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene. Breast Cancer Res. Treat. 48:265–271.

    PubMed  Google Scholar 

  70. I. G. Maroulakou, M. Anver, L. Garrett, and J. E. Green (1994). Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc. Natl. Acad. Sci. U.S.A. 91:11236–11240.

    PubMed  Google Scholar 

  71. J. S. Lee, R. A. Newman, S. M. Lippman, M. H. Huber, T. Minor, M. N. Raber, I. H. Krakoff, and W. K. Hong (1993). Phase I Evaluation of all-trans-retinoic acid in adults with solid tumors. J. Clinical Oncol. 11:959–966.

    Google Scholar 

  72. L. M. Sutton, M. A. Warmith, W. P. Petros, and E. P. Winer (1997). Pharmacokinetics and clinical impact of all-trans retinoic acid in metastatic breast canceer: A phase II trial. Cancer Chemother. Pharmacol. 40:335–341.

    PubMed  Google Scholar 

  73. J. Cassidy, M. Liffman, A. Lacroix, and G. Peck (1982). Phase II trial of 13–cis-retinoic acid in metastatic breast cancer. Eur. J. Cancer Clin. Oncol. 18:925–928.

    PubMed  Google Scholar 

  74. V. A. Miller, J. R. Rigas, F. M. Benedetti, A. L. Verret, W. P. Tong, M. G. Kris, G. M. Gill, G. R. Loewen, J. A. Truglia, E. H. Ulm, and R. P. Warrell, Jr., (1996). Initial clinical trial of the retinoid receptor pan agonist 9–cis-retinoic acid. Clinical Cancer Res. 2:471–475.

    Google Scholar 

  75. A. Costa, W. Malone, M. Perloff, F. Buranelli, T. Campa, G. Dossena, A. Magni, M. Pizzichetta, C. Andreoli, M. Del Vecchio, et al. (1989). Tolerability of the synthetic retinoid Fenretinide (HPR). Eur. J. Cancer Clin. Oncol. 25:805–808.

    PubMed  Google Scholar 

  76. M. R. Modiano, W. S. Dalton, S. M. Lippman, L. Joffe, A. R. Booth, and F. L. Meyskens, Jr. (1990). Phase II study of fenretinide (N-[4–hydroxyphenyl]retinamide) in advanced breast cancer and melanoma. Invest. New Drugs 8:317–319.

    PubMed  Google Scholar 

  77. V. A. Miller, F. M. Benedetti, J. R. Rigas, A. L. Verret, D. G. Pfister, D. Straus, M. G. Kris, M. Crisp, R. Heyman, G. R. Loewen, J. A. Truglia, and R. P. Warrell, Jr., (1997). Initial clinical trial of a selective retinoid X receptor ligand, LGD1069. J. Clinical Oncol. 15:790–795.

    Google Scholar 

  78. M. A. Cobleigh, K. Dowlatshihi, T. A. Deutsch, R. G. Mehta, R. C. Moon, F. Minn, A. B. Benson, III, A. W. Rademaker, J. B. Ashenhurst, J. L. Wade, III and J. Wolter (1993). Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer. J. Clinical Oncol. 11:474–477.

    Google Scholar 

  79. G. T. Budd, P. C. Adamson, M. Gupta, P. Homayoun, S. K. Sandstrom, R. F. Murphy, D. McLain, L. Tuason, D. Peereboom, R. M. Bukowski, and R. Ganapathi (1998). Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer. Clinical Cancer Res. 4:635–642.

    Google Scholar 

  80. F. Recchia, S. Rea, G. Corrao, A. Fingerhut, and L. Frati (1995). Sequential chemotherapy, β interferon, retinoids and tamoxifen in the treatment of metastatic breast cancer. A pilot study. Eur. J. Cancer 31A:1887–1888.

    PubMed  Google Scholar 

  81. F. Recchia, G. Sica, S. DeFilippis, S. Discepoli, S. Rea, P. Torchio, and L. Frati (1995). Interferon-β, retinoids, and tamoxifen in the treatment of metastatic breast cancer: A phase II study. J. Interferon Cytokine Res. 15:605–610.

    PubMed  Google Scholar 

  82. A. Costa, F. Formelli, F. Chiesa, A. Decensi, G. DePalo, and U. Veronesi (1994). Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide. Cancer Res. 54:2032s-2037s.

    PubMed  Google Scholar 

  83. U. Veronesi, G. DePalo, A. Costa, F. Formelli, E. Marubini, and M. DelVecchio (1992). Chemoprevention of breast cancer with retinoids. J. Natl. Cancer Institute Monographs 12:93–97.

    Google Scholar 

  84. G. De Palo, T. Camerini, E. Marubini, A. Costa, F. Formelli, M. DelVechio, L. Mariani, R. Miceli, G. Mascotti, A. Magni, T. Campa, M. G. DiMauro, A. Attili, C. Maltoni, M. R. DelTurco, A. Decensi, G. D'Aiuto, and U. Veronessi (1997). Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale, design, methodology, organization, data management, statistics and accrual. Tumori 83:884–894.

    PubMed  Google Scholar 

  85. A. Costa, G. DePalo, A. Decensi, F. Formelli, F. Chiesa, M. Nava, T. Camerini, E. Marubini, and U. Veronesi (1995). Retinoids in cancer chemoprevention, clinical trials with the synthetic analogue fenretinide. Ann. N. Y. Acad. Sci. 768:148–162.

    PubMed  Google Scholar 

  86. A. Costa, B. Boonanni, L. Manetti, A. G. Gonzaga, R. Torrisi, and A. Decensi (1998). Prevention of breast cancer: Focus on chemoprevention. Recent Results Cancer Res. 152:11–21.

    PubMed  Google Scholar 

  87. G. De Palo, U. Veronesi, T. Camerini, F. Formelli, G. Mascoti, C. Boni, V. Fosser, M. DelVecchio, T. Campa, A. Costa, and E. Marubini (1995). Can fenretinide protect women against ovarian cancer? J. Natl. Cancer Instit. 87:146–147.

    Google Scholar 

  88. L. M. Yang, D. Munoz-Medellin, H. T. Kim, J. Ostrowski, P. Reczek, and P. H. Brown (1999). Retinoic acid receptor antagonist BMS 453 inhibits the growth of normal and malignant breast cells without activating RAR-dependent gene expression. Breast Cancer Res. and Treat. 56:277–291.

    Google Scholar 

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Authors
  1. LiMin Yang
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  2. Caesar Tin-U
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  3. Kendall Wu
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  4. Powel Brown
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Yang, L., Tin-U, C., Wu, K. et al. Role of Retinoid Receptors in the Prevention and Treatment of Breast Cancer. J Mammary Gland Biol Neoplasia 4, 377–388 (1999). https://doi.org/10.1023/A:1018718401126

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