Hormonal therapy in gynecological sarcomas

Gynecological sarcomas are rare, constituting 3–5% of uterine malignancies. Endometrial stromal sarcomas and some uterine leiomyosarcomas are characterized by estrogen receptor (ER) and progesterone receptor (PgR) expression with variable impact on their clinical behavior and potential response to systemic therapies. A variety of hormonal treatments have been tested, since they act as targeted treatment against ER and PgR and have a tolerable side effect profile, which allows them to be administered for prolonged periods. Their role has been studied more extensively in endometrial stromal sarcomas, as the majority of cases are ER/PgR positive, while recently, an emerging role for hormonal manipulation has been described in ER/PgR-positive uterine leiomyosarcomas. Owing to the rarity and heterogeneous nature of uterine sarcomas, current treatment recommendations are based on small retrospective studies and case reports. This review comprises a critical appraisal of the existing data regarding hormonal manipulation in uterine sarcomas and attempts to make recommendations for endocrine treatments in specific settings, as well as suggest targets/medications for future research.

[1]  R. Barakat,et al.  Immunohistochemical expression of estrogen and progesterone receptors and outcomes in patients with newly diagnosed uterine leiomyosarcoma. , 2012, Gynecologic oncology.

[2]  E. Álava,et al.  Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  S. Kōzuma,et al.  Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report , 2011, Medical oncology.

[4]  G. Sonpavde,et al.  The role of abiraterone acetate in the management of prostate cancer: a critical analysis of the literature. , 2011, European Urology.

[5]  R. Coleman,et al.  Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy. , 2011, Gynecologic oncology.

[6]  M. Scurr.  Histology-Driven Chemotherapy in Soft Tissue Sarcomas , 2011, Current treatment options in oncology.

[7]  A. Koivisto,et al.  Immunohistochemical studies on uterine carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma: expression and prognostic importance of ten different markers , 2011, Tumor Biology.

[8]  C. Haie-meder,et al.  Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  E. Toy,et al.  Stage IA vs. IB endometrial stromal sarcoma: does the new staging system predict survival? , 2010, Gynecologic oncology.

[10]  M. Hensley.  Update on gemcitabine and docetaxel combination therapy for primary and metastatic sarcomas , 2010, Current opinion in oncology.

[11]  I. Judson,et al.  Guidelines for the management of soft tissue sarcomas . The British Sarcoma Group , 2010 .

[12]  J. Liu,et al.  Validation of Tumor Size as Staging Variable in the Revised International Federation of Gynecology and Obstetrics Stage I Leiomyosarcoma: A Population-Based Study , 2010, International Journal of Gynecologic Cancer.

[13]  A. Iasonos,et al.  Treatment of advanced uterine leiomyosarcoma with aromatase inhibitors. , 2010, Gynecologic oncology.

[14]  W. McCluggage,et al.  Mullerian Adenosarcoma of the Female Genital Tract , 2010, Advances in anatomic pathology.

[15]  C. Dunton,et al.  Treatment of Recurrent Endometrial Stromal Sarcoma with Letrozole: A Case Report and Literature Review , 2010, Hormones & cancer.

[16]  P. Casali,et al.  Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  J. Prat,et al.  Uterine sarcomas: a review. , 2010, Gynecologic Oncology.

[18]  B. Karlan,et al.  Hormone receptor expression in uterine sarcomas: prognostic and therapeutic roles. , 2009, Gynecologic oncology.

[19]  D. Timmerman,et al.  Clinical management of uterine sarcomas. , 2009, The Lancet. Oncology.

[20]  J. Prat,et al.  Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system. , 2009, Human pathology.

[21]  R. Broaddus,et al.  Phase 2 trial of mifepristone (RU‐486) in advanced or recurrent endometrioid adenocarcinoma or low‐grade endometrial stromal sarcoma , 2009, Cancer.

[22]  T. Dahhan,et al.  The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study. , 2009, European journal of obstetrics, gynecology, and reproductive biology.

[23]  J. Prat.  FIGO staging for uterine sarcomas , 2009, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[24]  J. Nesland,et al.  Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients , 2009, Histopathology.

[25]  R. Ali-Fehmi,et al.  Lymphadenectomy and Ovarian Preservation in Low-Grade Endometrial Stromal Sarcoma , 2008, Obstetrics and gynecology.

[26]  J. Chan,et al.  Endometrial stromal sarcoma: a population-based analysis , 2008, British Journal of Cancer.

[27]  J. Chan,et al.  Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas , 2008, Cancer.

[28]  Ning Li,et al.  Treatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases. , 2008, Gynecologic oncology.

[29]  A. Howell,et al.  Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. , 2008, Cancer treatment reviews.

[30]  B. Kim,et al.  Low-grade endometrial stromal sarcoma: a single center's experience with 22 cases , 2007, International Journal of Gynecologic Cancer.

[31]  B. van Calster,et al.  Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma , 2007, British Journal of Cancer.

[32]  A. Santin,et al.  Metastatic Uterine Leiomyosarcoma Regression Using an Aromatase Inhibitor , 2007, Obstetrics and gynecology.

[33]  S. Regauer,et al.  Hormonal therapy of endometrial stromal sarcoma , 2007, Current opinion in oncology.

[34]  R. Bristow,et al.  Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma. , 2007, Gynecologic oncology.

[35]  A. Leminen,et al.  Mifepristone as Treatment of Recurrent Progesterone Receptor–Positive Uterine Leiomyosarcoma , 2007, Obstetrics and gynecology.

[36]  S. Regauer,et al.  Estrogen replacement therapy and tamoxifen are contraindicated in patients with endometrial stromal sarcoma. , 2006, Gynecologic oncology.

[37]  B. Dörken,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. , 2006, Gynecologic oncology.

[38]  K. Hsu,et al.  Prognostic factors and impact of adjuvant chemotherapy for uterine leiomyosarcoma. , 2006, Gynecologic oncology.

[39]  S. Regauer,et al.  Survey of adjuvant hormone therapy in patients after endometrial stromal sarcoma. , 2006, European journal of gynaecological oncology.

[40]  V. Dandolu,et al.  Ovarian conservation at the time of hysterectomy for benign disease. , 2005, Obstetrics and gynecology.

[41]  Chung-Liang Ho,et al.  Discordant responses to progestin in a patient with uterine low‐grade smooth‐muscle tumors metastatic to the lung , 2005, The journal of obstetrics and gynaecology research.

[42]  S. Topuz,et al.  The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study. , 2005, Gynecologic oncology.

[43]  F. Nogales,et al.  Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study , 2005, Modern Pathology.

[44]  北岡 由衣.  Aromatase cytochrome P450 and estrogen and progesterone receptors in uterine sarcomas : correlation with clinical parameters , 2005 .

[45]  C. Bourgain,et al.  Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor letrozole. , 2004, Gynecologic oncology.

[46]  C. Burke,et al.  Treatment of Endometrial Stromal Sarcoma With a Gonadotropin-Releasing Hormone Analogue , 2004, Obstetrics and gynecology.

[47]  A. Olshen,et al.  Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma , 2004, Cancer.

[48]  V. Abeler,et al.  Immunohistochemical determination of estrogen and progesterone receptor positivity in uterine adenosarcoma. , 2004, Gynecologic oncology.

[49]  H. Denk,et al.  Expression of androgen receptors in benign and malignant endometrial stromal neoplasms , 2004, Virchows Archiv.

[50]  S. Regauer,et al.  Aromatase expression in low-grade endometrial stromal sarcomas: an immunohistochemical study , 2004, Modern Pathology.

[51]  J. Sakamoto,et al.  The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: Report of a case , 2004, Surgery Today.

[52]  S. Cha,et al.  Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. , 2003, Gynecologic oncology.

[53]  A. Hagemeijer,et al.  Endometrial stromal sarcoma presenting as postpartum haemorrhage: report of a case with a sole t(10;17)(q22;p13) translocation. , 2003, Gynecologic oncology.

[54]  G. Mor,et al.  Low-grade endometrial stromal sarcoma: hormonal aspects. , 2003, Gynecologic oncology.

[55]  S. Leodolter,et al.  Estrogen and progesterone receptor expression in patients with uterine leiomyosarcoma and correlation with different clinicopathological parameters. , 2003, Anticancer research.

[56]  J. Soria,et al.  Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma , 2003, Medical oncology.

[57]  R. Yates,et al.  A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers , 2002, British Journal of Cancer.

[58]  L. Berstein,et al.  Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects. , 2002, European journal of obstetrics, gynecology, and reproductive biology.

[59]  H. Gabra,et al.  CA125 response is associated with estrogen receptor expression in a phase II trial of letrozole in ovarian cancer: identification of an endocrine-sensitive subgroup. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[60]  D. Wysowski,et al.  Uterine sarcoma associated with tamoxifen use. , 2002, The New England journal of medicine.

[61]  J. Bryant,et al.  Association of tamoxifen and uterine sarcoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  L. Schwartz,et al.  Endometrial stromal sarcoma: objective response to letrozole. , 2001, Gynecologic oncology.

[63]  H. Hollema,et al.  Risk and prognosis of endometrial cancer after tamoxifen for breast cancer , 2000, The Lancet.

[64]  Donald P. McDonnell,et al.  The Opposing Transcriptional Activities of the Two Isoforms of the Human Progesterone Receptor Are Due to Differential Cofactor Binding , 2000, Molecular and Cellular Biology.

[65]  R. Demopoulos,et al.  Effects of leuprolide acetate on low-grade endometrial stromal sarcoma. , 2000, American journal of obstetrics and gynecology.

[66]  C. Haie-meder,et al.  Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma , 2000, Cancer.

[67]  S. Regauer,et al.  Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas , 2000, British Journal of Cancer.

[68]  J. Cerhan,et al.  Tamoxifen therapy for breast cancer and endometrial cancer risk. , 1999, Journal of the National Cancer Institute.

[69]  M. Uršič-Vrščaj.  Hormone replacement therapy after uterine leiomyosarcoma treatment. Case reports. , 1999, European journal of gynaecological oncology.

[70]  D. Scribner,et al.  Low-grade endometrial stromal sarcoma preoperative treatment with Depo-Lupron and Megace. , 1998, Gynecologic oncology.

[71]  P. Dombernowsky,et al.  Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  W. Thompson,et al.  Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus , 1996, Cancer.

[73]  P. Clement,et al.  Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. , 1990, Human pathology.

[74]  P. Schwartz,et al.  Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors. , 1987, Gynecologic oncology.

[75]  Ralph,et al.  A Clinicopathologic Study , 2006 .