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子宫内膜癌
Endometrial Cancer


Karen H. Lu ... 肿瘤 • 2020.11.19
相关阅读
• 局部晚期子宫内膜癌的辅助化疗联合放疗 • 接纳微创手术治疗子宫内膜癌 • 子宫内膜癌与母乳喂养:母乳喂养的又一益处

与美国其他大多数癌症的情况不同,子宫内膜癌的发病率和相关死亡率都在上升1(图1)。肥胖是子宫内膜癌最重要的危险因素之一,随着肥胖率的升高,子宫内膜癌的发病率也在上升。在过去几年间,子宫内膜癌的手术治疗已得到改进,现在的术式已将前哨淋巴结定位与子宫、输卵管和卵巢的标准微创切除术相结合。癌症基因组图谱(Cancer Genome Atlas,TCGA)项目获得的数据增进了我们对子宫内膜癌生物学异质性的认识4-6。这一新知识为复发性子宫内膜癌的靶向治疗提供了更多选择。但挑战仍然存在,包括在死亡率方面日益扩大的种族差异。随着美国肥胖率的持续上升,我们需要新的预防和治疗方案来控制不断增加的子宫内膜癌病例和相关死亡。





作者信息

Karen H. Lu, M.D., and Russell R. Broaddus, M.D., Ph.D.
From the Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas M.D. Anderson Cancer Center, Houston (K.H.L.); and the Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill (R.R.B.). Address reprint requests to Dr. Lu at the Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1362, Houston, TX 77030, or at khlu@mdanderson.org.

 

参考文献

1. Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer. I. National cancer statistics. Cancer 2020;126:2225-2249.

2. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet 2014;384:755-765.

3. Cirisano FD Jr, Robboy SJ, Dodge RK, et al. Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma. Gynecol Oncol 1999;74:385-394.

4. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497:67-73.

5. Liu Y, Patel L, Mills GB, et al. Clinical significance of CTNNB1 mutation and Wnt pathway activation in endometrioid endometrial carcinoma. J Natl Cancer Inst 2014;106(9):dju245-dju245.

6. Cherniack AD, Shen H, Walter V, et al. Integrated molecular characterization of uterine carcinosarcoma. Cancer Cell 2017;31:411-423.

7. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer — viewpoint of the IARC Working Group. N Engl J Med 2016;375:794-798.

8. Saed L, Varse F, Baradaran HR, et al. The effect of diabetes on the risk of endometrial cancer: an updated a systematic review and meta-analysis. BMC Cancer 2019;19:527-527.

9. Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2014;20:748-758.

10. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995;85:304-313.

11. Evans AT III, Gaffey TA, Malkasian GD Jr, Annegers JF. Clinicopathologic review of 118 granulosa and 82 theca cell tumors. Obstet Gynecol 1980;55:231-238.

12. Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 1999;91:1654-1662.

13. Swerdlow AJ, Jones ME. Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study. J Natl Cancer Inst 2005;97:375-384.

14. Brinton LA, Berman ML, Mortel R, et al. Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study. Am J Obstet Gynecol 1992;167:1317-1325.

15. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 2015;16:1061-1070.

16. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-591.

17. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569-578.

18. Pal N, Broaddus RR, Urbauer DL, et al. Treatment of low-risk endometrial cancer and complex atypical hyperplasia with the levonorgestrel-releasing intrauterine device. Obstet Gynecol 2018;131:109-116.

19. Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol 2012;125:477-482.

20. Westin SN, Fellman B, Sun CC, et al. Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer. Am J Obstet Gynecol 2020 August 15 (Epub ahead of print).

21. Møller P, Seppälä TT, Bernstein I, et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 2018;67:1306-1316.

22. Ryan NAJ, Morris J, Green K, et al. Association of mismatch repair mutation with age at cancer onset in Lynch syndrome: implications for stratified surveillance strategies. JAMA Oncol 2017;3:1702-1706.

23. Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 2006;66:7810-7817.

24. Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol 2007;25:5158-5164.

25. Schmeler KM, Lynch HT, Chen L, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006;354:261-269.

26. National Comprehensive Cancer Network. Uterine neoplasms, version 1. 2020 (https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. opens in new tab).

27. Committee on Practice Bulletins-Gynecology, Society of Gynecologic Oncology. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol 2014;124:1042-1054.

28. Cote ML, Ruterbusch JJ, Olson SH, Lu K, Ali-Fehmi R. The growing burden of endometrial cancer: a major racial disparity affecting black women. Cancer Epidemiol Biomarkers Prev 2015;24:1407-1415.

29. Clarke MA, Devesa SS, Harvey SV, Wentzensen N. Hysterectomy-corrected uterine corpus cancer incidence trends and differences in relative survival reveal racial disparities and rising rates of nonendometrioid cancers. J Clin Oncol 2019;37:1895-1908.

30. Doll KM, Winn AN. Assessing endometrial cancer risk among US women: long-term trends using hysterectomy-adjusted analysis. Am J Obstet Gynecol 2019;221(4):318.e1-318.e9.

31. Dubil EA, Tian C, Wang G, et al. Racial disparities in molecular subtypes of endometrial cancer. Gynecol Oncol 2018;149:106-116.

32. Rocconi RP, Lankes HA, Brady WE, et al. The role of racial genetic admixture with endometrial cancer outcomes: an NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 2016;140:264-269.

33. Bregar AJ, Alejandro Rauh-Hain J, Spencer R, et al. Disparities in receipt of care for high-grade endometrial cancer: a National Cancer Data Base analysis. Gynecol Oncol 2017;145:114-121.

34. Sud S, Holmes J, Eblan M, Chen R, Jones E. Clinical characteristics associated with racial disparities in endometrial cancer outcomes: a surveillance, epidemiology and end results analysis. Gynecol Oncol 2018;148:349-356.

35. Mukerji B, Baptiste C, Chen L, et al. Racial disparities in young women with endometrial cancer. Gynecol Oncol 2018;148:527-534.

36. Zaino RJ, Kurman RJ, Diana KL, Morrow CP. The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system: a Gynecologic Oncology Group study. Cancer 1995;75:81-86.

37. Tavassoli FA, Devilee P, eds. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon, France: IARC Press, 2003.

38. Slomovitz BM, Burke TW, Eifel PJ, et al. Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol 2003;91:463-469.

39. Malpica A, Tornos C, Burke TW, Silva EG. Low-stage clear-cell carcinoma of the endometrium. Am J Surg Pathol 1995;19:769-774.

40. Sreenan JJ, Hart WR. Carcinosarcomas of the female genital tract: a pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol 1995;19:666-674.

41. Thompson L, Chang B, Barsky SH. Monoclonal origins of malignant mixed tumors (carcinosarcomas): evidence for a divergent histogenesis. Am J Surg Pathol 1996;20:277-285.

42. Costa MJ, Vogelsan J, Young LJ. p53 Gene mutation in female genital tract carcinosarcomas (malignant mixed müllerian tumors): a clinicopathologic study of 74 cases. Mod Pathol 1994;7:619-627.

43. Abeln EC, Smit VT, Wessels JW, de Leeuw WJ, Cornelisse CJ, Fleuren GJ. Molecular genetic evidence for the conversion hypothesis of the origin of malignant mixed Müllerian tumours. J Pathol 1997;183:424-431.

44. Kounelis S, Jones MW, Papadaki H, Bakker A, Swalsky P, Finkelstein SD. Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components. Hum Pathol 1998;29:82-87.

45. George E, Lillemoe TJ, Twiggs LB, Perrone T. Malignant mixed müllerian tumor versus high-grade endometrial carcinoma and aggressive variants of endometrial carcinoma: a comparative analysis of survival. Int J Gynecol Pathol 1995;14:39-44.

46. Vaidya AP, Horowitz NS, Oliva E, Halpern EF, Duska LR. Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma. Gynecol Oncol 2006;103:684-687.

47. Le Gallo M, Rudd ML, Urick ME, et al. Somatic mutation profiles of clear cell endometrial tumors revealed by whole exome and targeted gene sequencing. Cancer 2017;123:3261-3268.

48. Kurnit KC, Kim GN, Fellman BM, et al. CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence. Mod Pathol 2017;30:1032-1041.

49. Costigan DC, Dong F, Nucci MR, Howitt BE. Clinicopathologic and immunohistochemical correlates of CTNNB1 mutated endometrial endometrioid carcinoma. Int J Gynecol Pathol 2020;39:119-127.

50. Moroney MR, Davies KD, Wilberger AC, et al. Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers. Gynecol Oncol 2019;153:517-520.

51. Myers A, Barry WT, Hirsch MS, Matulonis U, Lee L. β-Catenin mutations in recurrent FIGO IA grade I endometrioid endometrial cancers. Gynecol Oncol 2014;134:426-427.

52. Yano M, Ito K, Yabuno A, et al. Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma. Mod Pathol 2019;32:1023-1031.

53. He Y, Wang T, Li N, Yang B, Hu Y. Clinicopathological characteristics and prognostic value of POLE mutations in endometrial cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2020;99(8):e19281-e19281.

54. Wortman BG, Bosse T, Nout RA, et al. Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: evaluation of the pilot phase of the PORTEC-4a trial. Gynecol Oncol 2018;151:69-75.

55. Walker JL, Piedmonte MR, Spirtos NM, et al. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group study LAP2. J Clin Oncol 2009;27:5331-5336.

56. Janda M, Gebski V, Brand A, et al. Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial. Lancet Oncol 2010;11:772-780.

57. Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 study. J Clin Oncol 2012;30:695-700.

58. Janda M, Gebski V, Davies LC, et al. Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer: a randomized clinical trial. JAMA 2017;317:1224-1233.

59. Carlson JW, Kauderer J, Hutson A, et al. GOG 244 — the lymphedema and gynecologic cancer (LEG) study: incidence and risk factors in newly diagnosed patients. Gynecol Oncol 2020;156:467-474.

60. Frumovitz M, Plante M, Lee PS, et al. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Lancet Oncol 2018;19:1394-1403.

61. Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol 2017;18:384-392.

62. Soliman PT, Westin SN, Dioun S, et al. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecol Oncol 2017;146:234-239.

63. Kosary C. Cancer of the cervix uteri. In: Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, eds. Cancer survival among adults: US SEER program, 1988-2001, patient and tumor characteristics. SEER survival monograph. Bethesda, MD: National Cancer Institute, 2007. (NIH publication no. 07-6215.)

64. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744-751.

65. Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. Lancet 2000;355:1404-1411.

66. Nout RA, Smit VTHBM, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 2010;375:816-823.

67. Randall ME, Filiaci V, McMeekin DS, et al. Phase III trial: adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/carboplatin in high-intermediate and high-risk early stage endometrial cancer. J Clin Oncol 2019;37:1810-1818.

68. Fader AN, Starks D, Gehrig PA, et al. An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC). Gynecol Oncol 2009;115:244-248.

69. Kelly MG, O’malley DM, Hui P, et al. Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecol Oncol 2005;98:353-359.

70. Dietrich CS III, Modesitt SC, DePriest PD, et al. The efficacy of adjuvant platinum-based chemotherapy in stage I uterine papillary serous carcinoma (UPSC). Gynecol Oncol 2005;99:557-563.

71. Powell MA, Filiaci VL, Hensley ML, et al. A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: an NRG Oncology trial. J Clin Oncol 2019;37:5500-5500. abstract.

72. de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2018;19:295-309.

73. de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol 2019;20:1273-1285.

74. Matei D, Filiaci V, Randall ME, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med 2019;380:2317-2326.

75. León-Castillo A, de Boer SM, Powell ME, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol 2020;38:3388-3397.

76. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol 2018;36:2044-2051.

77. Miller DS, Filiaci VL, Mannel RS, et al. Carboplatin and paclitaxel for advanced endometrial cancer: final overall survival and adverse event analysis of a phase III trial (NRG Oncology/GOG0209). J Clin Oncol 2020 September 29 (Epub ahead of print).

78. Aghajanian C, Filiaci V, Dizon DS, et al. A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Gynecol Oncol 2018;150:274-281.

79. Lorusso D, Ferrandina G, Colombo N, et al. Carboplatin-paclitaxel compared to carboplatin-paclitaxel-bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 — a randomized phase II trial. Gynecol Oncol 2019;155:406-412.

80. Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med 1961;264:216-222.

81. Fiorica JV, Brunetto VL, Hanjani P, Lentz SS, Mannel R, Andersen W. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2004;92:10-14.

82. Slomovitz BM, Jiang Y, Yates MS, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol 2015;33:930-936.

83. Soliman PT, Westin SN, Iglesias DA, et al. Everolimus, letrozole, and metformin in women with advanced or recurrent endometrioid endometrial cancer: a multi-center, single arm, phase II study. Clin Cancer Res 2020;26:581-587.

84. Slomovitz BM, Filiaci VL, Coleman RL, et al. GOG 3007, a randomized phase II (RP2) trial of everolimus and letrozole (EL) or hormonal therapy (medroxyprogesterone acetate/tamoxifen, PT) in women with advanced, persistent or recurrent endometrial carcinoma (EC): a GOG Foundation study. Gynecol Oncol 2018;149:2-2. abstract.

85. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 2020;38:1-10.

86. Makker V, Rasco D, Vogelzang NJ, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2019;20:711-718.

87. Soliman PT, Bassett RL Jr, Wilson EB, et al. Limited public knowledge of obesity and endometrial cancer risk: what women know. Obstet Gynecol 2008;112:835-842.

88. Washington CR, Haggerty A, Ronner W, Neff PM, Ko EM. Knowledge of endometrial cancer risk factors in a general gynecologic population. Gynecol Oncol 2020;158:137-142.

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