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Gynaecological Cancer


letrozole and two to anastrazole. One of these patients has had a complete response and two have stable disease. Five-year actuarial survival was 65%, with no difference in survival between patients presenting with metastases and patients without metastases.21


Researchers at Sloan-Kettering Memorial Center reported that recurrent endometrial sarcomas treated with hormonal therapy had a 50% response rate and prolonged survival.10


One of the larger studies


involved 20 LGESS patients; one patient received progestins after surgical resection and did not recur. Five patients who did not receive any adjuvant therapy recurred; two patients subsequently treated with progestins and chemotherapy survived versus three who were treated with radiation and died. Four patients in this series with stage III and IV LGESS received progestins and subsequently remained disease-free.8 Pink et al. reported on 10 patients with metastatic LGESS. Of the 10 patients, five were on oestrogen replacement therapy and three were on tamoxifen at the time of recurrence, again demonstrating the trophic effect of oestrogen on these tumours. Three patients were removed from oestrogen stimulation and remained stable, while two of three patients responded to progestins.7


Chu et al. reported on 22 patients with LGESS. Out of 22 patients, 10 patients recurred; of these 10, four had been on progestins and six had not. Subsequently, eight patients were put on progestins and seven of the eight responded to treatment.6


Another study looked at the


These retrospective studies have consistently demonstrated a benefit to treatment of metastatic LGESS with hormone therapy.


treatment of 11 cases of metastatic or recurrent endometrial sarcomas with hormonal therapy: 10 of 11 responded or remained stable.13


The most widely used agents in hormonal therapy are progestins, primarily medroxyprogesterone acetate and megestrol acetate, which function by downregulating ERs, increasing oestrogen metabolism, and inhibiting oestrogen-induced growth factors.5


LGESS that recur have


been shown to regress or stabilise under progestin treatment and may undergo complete remission.7,10 progestins can prevent recurrences.5,6


Studies have also shown that High-dose progestin therapy may


be associated with side effects, including weight gain, depression and thromboembolic episodes. To avoid the side effects associated with high-dose progestin treatment, other, newer drugs have been explored. Aromatase inhibitors commonly used in breast cancer treatment have


1. D’Angelo E, Prat J, Uterine sarcomas: a review, Gynecol Oncol, 2010;116:131–9.


2. Ihnen M, Mahner S, Jänicke F, Schwarz J, Current treatment options in uterine endometrial stromal sarcoma: report of a case review of the literature, Int J Gynecol Cancer, 2007;17:957–63


3. Ioffe YJ, Li AJ, Walsh C, et al., Hormone receptor expression in uterine sarcomas: prognostic and therapeutic roles, Gynecol Oncol, 2009;115:466–71.


4. Garrett A, Quinn MA, Hormonal therapies and gynaecological cancers, Best Pract Res Clin Obstet Gynaecol, 2008;22:407–21.


5. Reich O, Regauer S, Hormonal therapy of endometrial stromal sarcoma, Curr Opin Oncol, 2007;19:347–52.


6. Chu MC, Mor G, Lim C, et al., Low-grade endometrial stromal sarcoma: hormonal aspects, Gynecol Oncol, 2003;90:170–6.


7. Pink D, Lindner T, Mrozek A, et al., Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature, Gynecol Oncol, 2006;101:464–9.


8. Gadducci A, Sartori E, Landoni F, et al., Endometrial stromal sarcoma: analysis of treatment failures and survival, Gynecol Oncol, 1996;63:247–53.


9. Haberal A, Kayikçio ˘glu F, Boran N, et al., Endometrial


been applied to the treatment of LGESS. They reduce oestrogen by inhibiting oestrogen synthesis at peripheral sites. The early-generation aromatase inhibitors had many side effects, but third-generation drugs such as exemestane and letrozole and the steroidal aromatase inhibitor anastrazole have minimal toxicity. The dosages used for breast cancer treatment have been applied to off-label use in endometrial sarcomas.5 To highlight the effectiveness of these hormone treatments, it has been reported that two patients with lung metastases had complete remissions after treatment.22


Aromatase inhibitors are clearly effective and may be utilised primarily or as a potential second-line agent.3,5


Tamoxifen is contraindicated as it has an actual agonist effect on endometrial stromal cells. Studies have repeatedly shown that patients who receive oestrogen replacement therapy or tamoxifen have a higher risk of recurrence. Also, endometrial sarcomas have been reported as a consequence of tamoxifen use in breast cancer treatment.5,7


Leuprolide is an example of the GnRH analogues that have been used in the treatment of pre-menopausal patients with endometriosis and those with breast cancer. These drugs reduce and suppress ovarian oestrogen production.5


stage I sarcomas with treatment.23


Studies have shown successful reduction of All of these studies provide positive


data to support the use of hormonal therapy for the treatment and prevention of recurrences. Although there are no guidelines developed for the optimal drug, dose and time-frame for usage, it may be reasonable to use hormone therapy for all surgically resected receptor-positive LGESS, as commonly applied in breast carcinoma.


Conclusion


Endometrial stromal sarcomas are interesting and uncommon tumours of the uterus. Guidelines in terms of recommended treatment remain problematic, given the paucity of cases. It is advisable to test all tumours for OR and PR since this forms the basis for hormonal treatment. Patients with advanced-stage or metastatic LGESS should be treated post-operatively with hormonal treatment. Choices include progestins or aromatase inhibitors. If progression occurs, patients can be crossed over to another agent. At this time it is unclear whether patients with stage I tumours benefit from adjuvant treatment; low- dose progestins or close observation both seem to be reasonable options. Follow-up should be continued indefinitely, as recurrences often occur many years later. n


stromal sarcoma of the uterus: analysis of 25 patients, Eur J Obstet Gynecol Reprod Biol, 2003;109:209–13.


10. Berchuck A, Rubin SC, Hoskins WJ, et al., Treatment of endometrial stromal tumors, Gynecol Oncol, 1990;36:60–5.


11. De Fusco PA, Gaffey TA, Malkasian GD Jr, et al., Endometrial stromal sarcoma: review of Mayo Clinic experience, 1945– 1980, Gynecol Oncol, 1989;35:8–14.


12. Geller MA, Argenta P, Bradley W, et al., Treatment and recurrence patterns in endometrial stromal sarcomas and the relation to c-kit expression, Gynecol Oncol, 2004;95:632–6.


13. Dahhan T, Fons G, Buist MR, et al., The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study, Eur J Obstet Gynecol Reprod Biol, 2009;144:80–4.


14. Bodner K, Bodner-Adler B, Obermair A, et al., Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study in 31 patients, Gynecol Oncol, 2001;81:160–5.


15. Reich O, Winter R, Regauer S, et al., Should lymphadenectomy be performed in patients with endometrial stromal sarcomas, Gynecol Oncol, 2005;97:982.


16. Li AJ, Giuntoli RL 2nd, Drake R, et al., Ovarian preservation in stage I low-grade endometrial stromal sarcomas, Obstet Gynecol, 2005;106:1304–8.


17. Weitmann HD, Knocke TH, Kucera H, et al., Radiation therapy in the treatment of endometrial stromal sarcoma, Int J Radiat Oncol Biol Phys, 2001;49:739–48.


18. Sutton G, Brunetto VL, Kilgore L, et al., A phase II trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Groups Study, Gynecol Oncol, 2000;79:147–53.


19. Wade K, Quinn MA, Hammond I, et al., Uterine sarcoma: steroid receptors and response to hormonal therapy, Gynecol Oncol, 1990;39:364–7.


20. Reich O, Regauer S, Urdl W, et al., Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas, Br J Cancer, 2000;82:1030–4.


21. Terada KY, Davis J, Hormonal treatment of endometrial stromal sarcoma, J Clin Oncol, 2009;27 (Suppl; abstr e16576). Available at: www.asco.org/ascov2/Meetings/Abstracts?& vmview=abst_detail_view&confID=65&abstractID=30210 (accessed 14 April 2011).


22. Spano JP, Soria JC, Kambouchner M, et al., Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma, Med Oncol, 2003;20:87–93.


23. Burke C, Hickey K, Treatment of endometrial stromal sarcoma with a gonadotropin-releasing hormone analogue, Obstet Gynecol, 2004;104:1182–4.


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EUROPEAN ONCOLOGY & HAEMATOLOGY


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