Past, present, and future of hormonal therapy in recurrent endometrial cancer

Matthew J Carlson, Kristina W Thiel, Kimberly K Leslie, Matthew J Carlson, Kristina W Thiel, Kimberly K Leslie

Abstract

Endometrial cancer is a heterogeneous disease. Type I cancers are hormonally driven, typically present with a low grade at an early stage, and are of endometrioid histology. These cancers are often cured by surgery, and the rate of recurrence is low. Type II cancers are less differentiated, often appear at a later stage, and are of serous, clear cell, or high grade endometrioid histology. The risk of recurrence in these cancers is much higher than with type I tumors. Isolated pelvic recurrences can be treated with radiation or exenteration, but systemic disease is fatal. It is in these recurrent patients, where prolongation of progression-free survival is the goal, that hormonal therapy can have the greatest benefit. In selected patients, hormonal therapy can be as effective as cytotoxic chemotherapy, without the toxicity and at a much lower cost. Here we review the evidence for treatment of patients suffering from recurrent endometrial cancer with hormonal therapy and explore avenues for the future of hormonal treatment of endometrial cancer. Currently, progesterone is the hormonal treatment of choice in these patients. Other drugs are also used, including selective estrogen receptor modulators, aromatase inhibitors, and gonadotropin-releasing hormone antagonists. Hormonal treatment of recurrent endometrial cancer relies on expression of the hormone receptors, which act as nuclear transcription factors. Tumors that express these receptors are the most sensitive to therapy; it is for this reason that patient selection is vitally important to the successful treatment of recurrent endometrial cancer with hormonal therapy.

Keywords: hormonal therapy; recurrent endometrial cancer.

References

    1. Trimble EL, Harlan LC, Clegg LX, Stevens JL. Pre-operative imaging, surgery and adjuvant therapy for women diagnosed with cancer of the corpus uteri in community practice in the United States. Gynecol Oncol. 2005;96(3):741–748.
    1. Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95(Suppl 1):S105–S143.
    1. 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(32):5331–5336.
    1. Miller D, Filiaci V, Fleming G, et al. Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2012;125(3):771.
    1. Curran WJ, Jr, Whittington R, Peters AJ, Fanning J. Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system. Int J Radiat Oncol Biol Phys. 1988;15(4):803–808.
    1. Sears JD, Greven KM, Hoen HM, Randall ME. Prognostic factors and treatment outcome for patients with locally recurrent endometrial cancer. Cancer. 1994;74(4):1303–1308.
    1. Wylie J, Irwin C, Pintilie M, et al. Results of radical radiotherapy for recurrent endometrial cancer. Gynecol Oncol. 2000;77(1):66–72.
    1. Levine DA, Hoskins WJ. Update in the management of endometrial cancer. Cancer J. 2002;8(Suppl 1):S31–S40.
    1. Sonoda Y. Optimal therapy and management of endometrial cancer. Expert Rev Anticancer Ther. 2003;3(1):37–47.
    1. Yang S, Thiel KW, De Geest K, Leslie KK. Endometrial cancer: reviving progesterone therapy in the molecular age. Discov Med. 2011;12(64):205–212.
    1. Yang S, Thiel KW, Leslie KK. Progesterone: the ultimate endometrial tumor suppressor. Trends Endocrinol Metab. 2011;22(4):145–152.
    1. Thigpen JT, Brady MF, Alvarez RD, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999;17(6):1736–1744.
    1. Whitney CW, Brunetto VL, Zaino RJ, et al. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(1):4–9.
    1. Leslie KK, Sill MW, Fischer E, et al. A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129(3):486–494.
    1. Singh M, Zaino RJ, Filiaci VJ, Leslie KK. Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol. 2007;106(2):325–333.
    1. Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007;17(5):964–978.
    1. Markman M. Hormonal therapy of endometrial cancer. Eur J Cancer. 2005;41(5):673–675.
    1. Yang S, Xiao X, Jia Y, et al. Epigenetic modification restores functional PR expression in endometrial cancer cells. Curr Pharm Des. Jul 19, 2013. [Epub ahead of print.]
    1. Allen NE, Tsilidis KK, Key TJ, et al. Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol. 2010;172(12):1394–1403.
    1. Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001;19(2):364–367.
    1. Elit L, Hirte H. Novel strategies for systemic treatment of endometrial cancer. Expert Opin Investig Drugs. 2000;9(12):2831–2853.
    1. McMeekin DS, Gordon A, Fowler J, et al. A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer. Gynecol Oncol. 2003;90(1):64–69.
    1. Burke TW, Walker CL. Arzoxifene as therapy for endometrial cancer. Gynecol Oncol. 2003 Aug;90(2 Pt 2):S40–S46.
    1. Asbury RF, Brunetto VL, Lee RB, Reid G, Rocereto TF, Gynecologic Oncology Group Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Am J Clin Oncol. 2002;25(6):557–560.
    1. Che Q, Liu BY, Liao Y, et al. Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17beta-estradiol biosynthesis in endometrial carcinoma microenvironment. Int J Cancer. Dec 18, 2013. [Epub ahead of print.]
    1. Takahashi-Shiga N, Utsunomiya H, Miki Y, et al. Local biosynthesis of estrogen in human endometrial carcinoma through tumor-stromal cell interactions. Clin Cancer Res. 2009;15(19):6028–6034.
    1. Segawa T, Shozu M, Murakami K, et al. Aromatase expression in stromal cells of endometrioid endometrial cancer correlates with poor survival. Clin Cancer Res. 2005;11(6):2188–2194.
    1. Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000;78(2):212–216.
    1. Ma BB, Oza A, Eisenhauer E, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer. 2004;14(4):650–658.
    1. Soslow RA, Wethington SL, Cesari M, et al. Clinicopathologic analysis of matched primary and recurrent endometrial carcinoma. Am J Surg Pathol. 2012;36(12):1771–1781.
    1. Robertson JFR, Willsher PC, Winterbottom L, Blamey RW, Thorpe S. Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer. 1999;35(2):214–218.
    1. Schneider CC, Gibb RK, Taylor DD, Wan T, Gercel-Taylor C. Inhibition of endometrial cancer cell lines by mifepristone (RU 486) J Soc Gynecol Investig. 1998;5(6):334–338.
    1. Jordan VC. New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer. Steroids. 2007;72(13):829–842.
    1. Sasaki M, Dharia A, Oh BR, Tanaka Y, Fujimoto S, Dahiya R. Progesterone receptor B gene inactivation and CpG hypermethylation in human uterine endometrial cancer. Cancer Res. 2001;61(1):97–102.
    1. Xiong Y, Dowdy SC, Gonzalez Bosquet J, et al. Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines. Gynecol Oncol. 2005;99(1):135–141.
    1. Ren Y, Liu X, Ma D, Feng Y, Zhong N. Down-regulation of the progesterone receptor by the methylation of progesterone receptor gene in endometrial cancer cells. Cancer Genet Cytogenet. 2007;175(2):107–116.
    1. Dai D, Albitar L, Nguyen T, Laidler LL, Singh M, Leslie KK. A therapeutic model for advanced endometrial cancer: systemic progestin in combination with local adenoviral-mediated progesterone receptor expression. Mol Cancer Ther. 2005;4(1):169–175.
    1. Cancer Genome Atlas Research Network. Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.
    1. Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT. High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 1996;14(2):357–361.
    1. Fiorica JV, Brunetto VL, Hanjani P, et al. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(1):10–14.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren