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化学进展 2013, Vol. 25 Issue (09): 1429-1449 DOI: 10.7536/PC130747 前一篇   后一篇

所属专题： 酶化学

• 癌症化学预防专辑 •

乳腺癌预防的三期临床试验：雌激素靶向药物,选择性雌激素受体调控剂和芳香酶抑制剂

Barbara K. Dunn*   

  1. Medical Officer, National Cancer Institute, Division of Cancer Prevention
  • 收稿日期:2013-04-06 出版日期:2013-09-25 发布日期:2013-07-31
  • 通讯作者: Barbara K. Dunn E-mail:dunnb@mail.nih.gov
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Phase 3 Trials in Breast Cancer Prevention：Focus on Estrogen-Targeting Agents, Selective Estrogen Receptor Modulators and Aromatase Inhibitors

Barbara K. Dunn*   

  1. Medical Officer, National Cancer Institute, Division of Cancer Prevention
  • Received:2013-04-06 Online:2013-09-25 Published:2013-07-31
  • Contact: Barbara K. Dunn E-mail:dunnb@mail.nih.gov

据估计,2008 年全世界有138 万新诊断的乳腺癌,占女性所有癌症的23%,是世界范围内女性中最常见的癌症。尽管早期诊断和治疗技术的进步已经降低了乳腺癌的发病率和死亡率,但乳腺癌仍然是女性中死亡率最高的癌症。因此,探索预防乳腺癌的途径和开发风险评估模型以确定最可能从预防性干预中受益的女性具有重要意义。大规模临床试验是评估乳腺癌预防药物功效的金标准,同时也是这些药物获得正式批准的基础。因此,本文重点讨论了已经进入三期临床试验或已获正式批准用于降低乳腺癌风险的药物,尤其是针对雌激素受体阳性乳腺癌的预防药物如选择性雌激素受体调控剂和芳香酶抑制剂等;此外也对乳腺癌风险评估模型进行了简单评述。

关键词： 乳腺癌预防, 选择性雌激素受体调控剂, 芳香酶抑制剂, 三期临床试验, 风险评估模型

Worldwide, breast cancer is the most common cancer in women, with 1.38 million breast cancer diagnoses cases estimated for 2008, accounting for 23% of all cancers in women. Breast cancer has the highest mortality rate of all cancers among women worldwide. Although technological advances in early detection and treatment have made inroads into these rates, breast cancer associated mortality remains high. Hence, interest has emerged in exploring approaches to preventing this disease and developing risk models to identify women most likely to benefit from preventive interventions. The current chapter addresses breast cancer risk-reducing agents that have progressed in their development to testing in phase Ⅲ clinical trials or in some cases to formal approval for a breast cancer risk reduction indication. The discussion here concentrates on agents targeting estrogen receptor (ER)-positive breast cancers, specifically selective ER modulators (SERMs) and aromatase inhibitors (AIs). The large phase III clinical trials assessing efficacy of these agents in breast cancer prevention are the focus, as these represent the gold standard in clinical testing and serve as the basis for approval of these anti-estrogens for risk reduction of breast cancer among high-risk women.

Key words: breast cancer prevention, selective estrogen receptor modulators, aromatase inhibitors, phase Ⅲ clinical trials, risk models

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[1] Ferlay J, Shin H R, Bray F, Forman D, Mathers C, Parkin D M. Int. J. Cancer., 2010, 127: 2893—2917
[2] Cancer Research U K. Cancer Stats.Breast Cancer 2011.[2013-03-18]. http://www.cancerresearchuk.org/cancer-info/cancerstats/world/breast-cancer-world/#Mortality
[3] Siegel R, Naishadham D, Jemal A. CA Cancer J. Clin., 2013, 63:11—30
[4] Nelson H D, Huffman L H, Fu R, Harris E L. Ann. Intern. Med., 2005, 143: 362—379
[5] Kurian A W, Gong G D, Chun N M, Mills M A, Staton A D, Kingham K E, Crawford B B, Lee R, Chan S, Donlon S S, Ridge Y, Panabaker K, West D W, Whittemore A S, Ford J M. J. Clin. Oncol., 2008, 26: 4752—4758
[6] Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans D G. J. Intern. Med., 2012, 271: 321—330
[7] Boughey J C, Hartmann L C, Anderson S S, Degnim A C, Vierkant R A, Reynolds C A, Frost M H, Pankratz V S. J. Clin. Oncol., 2010, 28: 3591—3596
[8] Baker L H. CA Cancer J. Clin., 1982, 32: 194—225
[9] Gail M H, Brinton L A, Byar D P, Corle D K, Green S B, Schairer C, Mulvihill J J. J. Natl. Cancer Inst., 1989, 81: 1879—1886
[10] Costantino J P, Gail M H, Pee D, Anderson S, Redmond C K, Benichou J, Wieand H S. J. Natl. Cancer Inst., 1999, 91: 1541—1548
[11] NCI Breast Cancer Risk Assessment Tool. 2011, (2012-05-16).[2013-03-19]. http://www.cancer.gov/bcrisktool/
[12] Gail M H. J. Natl. Cancer Inst., 2008, 100: 1037—1041
[13] Wacholder S, Hartge P, Prentice R, Garcia-Closas M, Feigelson H S, Diver W R, Thun M J, Cox D G, Hankinson S E, Kraft P, Rosner B, Berg C D, Brinton L A, Lissowska J, Sherman M E, Chlebowski R, Kooperberg C, Jackson R D, Buckman D W, Hui P, Pfeiffer R, Jacobs K B, Thomas G D, Hoover R N, Gail M H, Chanock S J, Hunter D J. N. Engl. J. Med., 2010, 362: 986—993
[14] Arun B, Dunn B K, Ford L G, Ryan A. Semin. Oncol., 2010, 37: 367—383
[15] Jordan V C, Ed. Tamoxifen. A Guide for Clinicians and Patients. Huntington, NY: PRR, Inc., 1996
[16] Nayfield S G, Karp J E, Ford L G, Dorr F A, Kramer B S. J. Natl. Cancer Inst., 1991, 83: 1450—1459
[17] Early Breast Cancer Trialists' Collaborative Group. Lancet, 1998, 351: 1451—1467.
[18] Early Breast Cancer Trialists' Collaborative Group. Lancet, 2005, 365: 1687—1717
[19] Fisher B, Costantino J, Redmond C, et al. N. Engl. J. Med., 1989, 320: 479—484
[20] Fisher B, Costantino J P, Wickerham D L, et al. J. Natl. Cancer Inst., 1998, 90: 1371—1388
[21] Fisher B, Costantino J P, Wickerham D L, et al. J. Natl. Cancer Inst., 2005, 97: 1652—1662
[22] Powles T, Eeles R, Ashley S, et al. Lancet, 1998, 352: 98—101
[23] Powles T J, Ashley S, Tidy A, Smith I E, Dowsett M. J. Natl. Cancer Inst., 2007, 99: 283—290
[24] Veronesi U, Maisonneuve P, Costa A, et al. Lancet, 1998, 352: 93—97
[25] Veronesi U, Maisonneuve P, Rotmensz N, et al. J. Natl. Cancer Inst., 2003, 95: 160—165
[26] Cuzick J, Forbes J, Edwards R, et al. Lancet, 2002, 360: 817—824
[27] Cuzick J. Eur. J. Cancer, 1998, 34: 1647—1648
[28] Cuzick J, Forbes J F, Sestak I, et al. J. Natl. Cancer Inst., 2007, 99: 272—282
[29] Cuzick J, Powles T, Veronesi U, et al. Lancet, 2003, 361: 296—300
[30] Ettinger B, Black D M, Mitlak B H, et al. JAMA, 1999, 282: 637—645
[31] Cummings S R, Eckert S, Krueger K A, et al. JAMA, 1999, 281: 2189—2197
[32] Vogel V G, Costantino J P, Wickerham D L, et al. JAMA, 2006, 295: 2727—2741
[33] Vogel V G, Costantino J P, Wickerham D L, et al. Cancer Prev. Res. (Phila), 2010, 3: 696—706
[34] Cuzick J. Cancer Prev. Res. (Phila), 2010, 3: 689—691
[35] Cummings S R, Ensrud K, Delmas P D, LaCroix A Z, Vukicevic S, Reid D M, Goldstein S, Sriram U, Lee A, Thompson J, Armstrong R A, Thompson D D, Powles T, Zanchetta J, Kendler D, Neven P, Eastell R. PEARL Study Investigators. N. Engl. J. Med., 2010, 362: 686—696
[36] LaCroix A Z, Powles T, Osborne C K, Wolter K, Thompson J R, Thompson D D, Allred D C, Armstrong R, Cummings S R, Eastell R, Ensrud K E, Goss P, Lee A,Neven P, Reid D M, Curto M, Vukicevic S. PEARL Investigators. J. Natl. Cancer Inst., 2010, 102: 1706—1715
[37] Cummings S R, McClung M, Reginster J Y, Cox D, Mitlak B, Stock J, Amewou-Atisso M, Powles T, Miller P, Zanchetta J, Christiansen C. J. Bone Miner. Res., 2011, 26: 397—404
[38] Coombes R C, Hall E, Gibson L J, Paridaens R, Jassem J, Delozier T, Jones S E, Alvarez I, Bertelli G, Ortmann O, Coates A S, Bajetta E, Dodwell D, Coleman R E, Fallowfield L J, Mickiewicz E, Andersen J, Lønning P E, Cocconi G, Stewart A, Stuart N, Snowdon C F, Carpentieri M, Massimini G, Bliss J M, vande Velde C. Intergroup Exemestane Study. N. Engl. J. Med., 2004, 350: 1081—1092
[39] Coombes RC, Kilburn LS, Snowdon CF, et al. Lancet, 2007, 369:559—570
[40] Richardson H, Johnston D, Pater J, Goss P. Curr. Oncol., 2007, 14: 89—96
[41] Khuder S A, Mutgi A B. Br. J. Cancer, 2001, 84: 1188—1192
[42] Hwang D, Scollard D, Byrne J, Levine E. J. Natl. Cancer Inst., 1998, 90: 455—460
[43] Bresalier R S, Sandler R S, Quan H, et al. N. Engl. J. Med., 2005, 352: 1092—1102
[44] Solomon S D, McMurray J J, Pfeffer M A, et al. N. Engl. J. Med., 2005, 352: 1071—1080
[45] Goss P E, Ingle J N, Ales-Martinez J E, et al. N. Engl. J. Med., 2011, 364: 2381—2391
[46] Decensi A, Dunn B K, Puntoni M, Gennari A, Ford L G. Cancer Discovery, 2012, 2: 25—40
[47] Baum M, Budzar A U, Cuzick J, Forbes J, Houghton J H, Klijn J G, Sahmoud T. ATAC Trialists' Group. Lancet, 2002, 359: 2131—2139
[48] Baum M, Buzdar A, Cuzick J, et al. Cancer, 2003, 98: 1802—1810
[49] Howell A, Cuzick J, Baum M, et al. Lancet, 2005, 365: 60—62
[50] Forbes J F, Cuzick J, Buzdar A, Howell A, Tobias J S, Baum M. Lancet Oncol., 2008, 9: 45—53
[51] Cuzick J, Sestak I, Baum M, et al. Lancet Oncol., 2010, 11: 1135—1141
[52] Sestak I, Cuzick J, Sapunar F, et al. Lancet Oncol., 2008, 9: 866—872
[53] Cuzick J. Recent Results Cancer Res., 2003, 163: 96—103; discussion 264—266
[54] Cuzick J. J. Clin. Oncol., 2005, 23: 1636—1643
[55] Cuzick J. Expert Rev. Anticancer Ther., 2008, 8: 1377—1385
[56] International Breast Cancer Intervention Study II. 2012,[2013-03-21]. http://www.ibis-trials.org/
[57] International Breast Cancer Intervention Study-II. Accrual numbers., 2012. [2013-04-03]. http://www.ibis-trials.org/news/viewStory.php?storyId=186
[58] Davies C, Pan H, Godwin J, et al. Lancet, 2013, 381(9869): 805—816
[59] Lazzeroni M, Serrano D, Dunn BK, et al. Breast Cancer Res., 2012,14:214
[60] Heckman-Stoddard B M, Lee O, Lazzeroni M, Khan S, DeCensi A, Dunn B K. Innovative Approaches to Tamoxifen Administration for Breast Cancer Prevention. In: Tamoxifen Concepts and Cancer: New Paradigms: Nova ScienceHauppauge. (Mello RAd, Ed.), NY: Publishers, 2013. in press.
[61] Decensi A, Bonanni B, Guerrieri-Gonzaga A, et al. J. Natl. Cancer Inst., 1998, 90: 1461—1467
[62] Decensi A, Gandini S, Guerrieri-Gonzaga A, et al. J. Clin. Oncol., 1999, 17: 2633—2638
[63] Decensi A, Robertson C, Viale G, et al. J. Natl. Cancer Inst., 2003, 95: 779—790
[64] Kisanga E R, Gjerde J, Guerrieri-Gonzaga A, et al. Clin. Cancer Res., 2004, 10: 2336—2343
[65] Decensi A, Robertson C, Guerrieri-Gonzaga A, et al. J. Clin. Oncol., 2009, 27: 3749—3756
[66] Waters E A, Cronin K A, Graubard B I, Han P K, Freedman A N. Cancer Epidemiol Biomarkers Prev., 2010, 19: 443—446
[67] Tchou J, Hou N, Rademaker A, Jordan V C, Morrow M. Cancer, 2004, 100: 1800—1806
[68] Decensi A, Puntoni M, Goodwin P, et al. Cancer Prev. Res. (Phila), 2010, 3: 1451—1461
[69] Bonanni B, Puntoni M, Cazzaniga M, et al. J. Clin. Oncol., 2012, 30(21): 2593—2600
[70] Szabo E. Semin. Oncol., 2010, 37: 359—366
[71] Goss P E, Ingle J N, Martino S, et al. N. Engl. J. Med., 2003, 349: 1793—1802
[72] Thurlimann B, Keshaviah A, Coates AS, et al. N. Engl. J. Med., 2005, 353: 2747—2757
[73] Coates A S, Keshaviah A, Thurlimann B, et al. J. Clin. Oncol., 2007, 25: 486—492
[74] Regan M M, Neven P, Giobbie-Hurder A, et al. Lancet Oncol., 2011, 12: 1101—1108
[75] Veronesi U, Maisonneuve P, Rotmensz N, et al. J. Natl. Cancer Inst., 2007, 99: 727—737otmensz N, et al. J. Natl. Cancer Inst., 2007, 99:727-737
[1] Michael B. Sporn, Karen T. Liby. 癌症化学预防：过去,现在和未来[J]. 化学进展, 2013, 25(09): 1421-1428.