***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma , who had no more than one prior line of progestins and never had chemotherapy ( except adjuvant ) . Archival paraffin-embedded tumor sample s were retrieved to determine the expression level of estrogen ( ER ) and progesterone receptor ( PgR ) , p53 , HER-2 , bcl-2 and PTEN protein , and phosphorylation status of protein kinase B ( PKB/Akt ) .  Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously , of whom 10 ( 31 % )  had prior progestins . Of the 28 patients evaluated for response , one complete and two partial responses were noted ; overall response was 9.4 % ( 95 % confidence interval 2–25 % ) . Eleven patients had stable disease for a median duration of 6.7 months ( range 3.7–19.3 months ) . Amongst 22 patients who had tumor blocks available , the proportion showing positive expression of the following markers includes : PgR ( 86 % ) , ER ( 86 % ) , PTEN ( 82 % ) , phosphorylated PKB/Akt ( 59 % ) , bcl-2 ( 45 % ) , p53 ( 32 % ) , and HER-2 ( 0 % ) . None of these markers correlated with response to letrozole or disease progression . In conclusion , letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer Background We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced , persistent or recurrent endometrial carcinoma . Methods We performed an open-label one-arm , two-stage , phase II study of 25 mg of oral exemestane in 51 patients with advanced ( FIGO stage III-IV ) or relapsed endometrioid endometrial cancer . Patients were stratified into subsets of estrogen receptor ( ER ) positive and ER negative patients . Results Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual . In the ER positive patients , we observed an overall response rate of 10 % , and a lack of progression after 6 months in 35 % of the patients . No responses were registered in the ER negative patients , and all had progressive disease within 6 months . For the total group of patients , the median progression free survival ( PFS ) was 3.1 months ( 95 % CI : 2.0 - 4.1 ) . In the ER positive patients the median PFS was 3.8 months ( 95 % CI : 0.7 - 6.9 ) and in the ER negative patients it was 2.6 months ( 95 % CI : 2.1 - 3 - 1 ) . In the ER positive patients the median overall survival ( OS ) time was 13.3 months ( 95 % CI : 7.7 - 18.9 ) , in the ER negative patients the corresponding numbers were 6.1 months ( 95 % CI : 4.1 - 8.2 ) . Treatment with exemestane was well tolerated . Conclusion Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane , an aromatase inhibitor , result ed in a response rate of 10 % and lack of progression after 6 months in 35 % of the patients .Trial registration Trial identification number ( Clinical Trials.gov ) : NCT01965080.Nordic Society of Gynecological Oncology : NSGO – EC–0302.EudraCT number : 2004 - 001103 - 35 OBJECTIVES The objectives of this study were to estimate the clinical response rate and toxicity of daily tamoxifen combined with intermittent weekly medroxyprogesterone acetate ( MPA ) . METHODS This study reports the results of 61 patients with measurable advanced or recurrent endometrial carcinoma enrolled on this study to be treated with tamoxifen 40 mg p.o . daily plus alternating weekly cycles of MPA 200 mg p.o . daily . RESULTS One patient was excluded and two patients did not receive study treatment . The percent of patients responding ( 6 complete and 13 partial ) was 33 % ( 95 % confidence interval [ CI ] : 21 - 46 % ) among 58 eligible patients who received therapy . Median progression-free survival ( PFS ) was 3 months and median overall survival ( OS ) was 13 months . CONCLUSION The combination of daily tamoxifen and intermittent weekly medroxyprogesterone acetate is an active treatment for advanced or recurrent endometrial carcinoma . Further investigation of this combination is appropriate Advanced uterine leiomyosarcoma ( ULMS ) is an incurable disease . A significant percentage of cases of ULMS express estrogen and /or progesterone receptors ( ER and /or PR ) . To the authors ' knowledge , the role of estrogen suppression in disease management is not known BACKGROUND Some endometrial cancers are hormonally dependent . A principal source of circulating estrogen is conversion of adrenal and rostenedione by aromatase . Anastrozole ( Arimidex ) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer . This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma . METHODS Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease , a GOG ( Zubrod ) performance status of < or = 2 , no more than one prior hormonal therapy regimen , and no prior chemotherapy were eligible .  Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days . RESULTS Twenty-three patients were entered on this trial . On central pathology review , 9 of them had grade 2 and 14 had grade 3 tumors . One to 24 courses ( median : 1 ) of therapy were administered . Two partial responses were noted ( 9 % ; 90 % confidence interval 3 to 23 % ) . Two additional patients had short-term stable disease . With the exception of 1 case of venous thrombosis , the toxicity profile was mild . Median duration s of progression-free survival and overall survival are 1 and 6 months , respectively . CONCLUSIONS Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer Estrogen-only  menopausal hormone therapy ( HT ) increases the risk of endometrial cancer , but less is known about the association with other types of HT . Using Cox proportional hazards regression , the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospect i ve Investigation into Cancer and Nutrition between 1992 and 2000 . After a mean follow-up period of 9 years , 601 incident cases of endometrial cancer were identified . In comparison with never users of  HT  , risk of endometrial cancer was increased among current users of estrogen-only HT ( hazard ratio ( HR ) = 2.52 , 95 % confidence interval ( CI ) : 1.77 , 3.57 ) , tibolone ( HR = 2.96 , 95 % CI : 1.67 , 5.26 ) , and , to a lesser extent , estrogen-plus-progestin HT ( HR = 1.41 , 95 % CI : 1.08 , 1.83 ) , although risks differed according to regimen and type of progestin constituent . The association of HT use with risk was stronger among women who were older , leaner , or had ever smoked cigarettes . The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk . The increased risk associated with tibolone use requires further investigation We have studied the response rates and survival of a group of 93 patients with Stage III or IV endometrial adenocarcinoma after r and om allocation to therapy with tamoxifen ( TAM ) 20 mg twice daily ( n = 45 ) or medroxyprogesterone acetate ( MPA ) 1 g/wk intramuscularly ( n = 48 ) . The patients were examined every 4 months . In the non-responders and in those who relapsed , combination therapy with TAM and MPA was given . Twenty-four of 45 ( 53.4 % ) responded to TAM alone , 27 of 48 ( 56.2 % ) responded to MPA alone . Of the responders 23 later relapsed in the TAM group and 24 in the MPA group and of these 14 ( 60.8 % ) and 15 ( 62.5 % ) , respectively , responded to the combination therapy . Of the original 21 non-responders to MPA alone , 10 responded to the combination ( 47.6 % ) and 11 ( 52.4 % ) did not ; the comparable figures for the TAM alone group were 13 ( 61.9 % ) and 8 ( 38.1 % ) , respectively . Survival rates were much higher in the differentiated than in the undifferentiated carcinomas . In conclusion , we feel that the efficacy , and the few side-effects of these drugs used alone and particularly when used in sequential combination , make them a very attractive treatment for advanced endometrial adenocarcinoma The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor , its clinical course , and the prognosis of the disease . On the basis of a prospect i ve study of 366 patients with endometrial carcinoma , the author postulates that there are two different pathogenetic types of endometrial carcinoma . The first pathogenetic type of the disease arises in women with obesity , hyperlipidemia , and signs of hyperestrogenism : anovulatory uterine bleeding , infertility , late onset of the menopause , and hyperplasia of the stroma of the ovaries and endometrium . The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined . The frequency of the first pathogenetic type in the studied group of women was 65 % , whereas the frequency of the second type was 35 % . The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors ( 82.3 % G1 and G2 ) , superficial invasion of the myometrium ( 69.4 % ) , high sensitivity to progestogens ( 80.2 % ) , and favorable prognosis ( 85.6 % 5-year survival rate ) . In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult , poorly differentiated tumors arise ( 62.5 % G3 ) , a tendency to deep invasion of tumor into the myometrium is observed ( 65.7 % ) ; high frequency of metastatic spread into the pelvic lymph nodes ( 27.8 % ) ; decrease of sensitivity to progestogens ( 42.5 % ) ; and doubtful prognosis ( 58.8 % 5-year survival rate ) are noted We evaluated the therapeutic value of sequential cyclical hormonal therapy ( megestrol acetate , and tamoxifen citrate ) plus single-agent chemotherapy ( carboplatin ) in the outpatient management of advanced or recurrent endometrial cancer .  Carboplatin ( 300 mg/m2 ) was administered every 4 weeks for six courses or until disease progression . In addition , patients alternated megestrol acetate ( 80 mg orally twice daily ) with tamoxifen citrate ( 20 mg orally twice daily ) every 3 weeks . Thirteen of 18 ( 72.2 % ) patients were considered evaluable . Four patients ( 30.8 % ) had a complete response , six ( 46.2 % ) had a partial response , one ( 7.7 % ) had stable disease , and two patients ( 15.4 % ) progressed . Six of seven patients with vaginal disease responded . The median progression-free interval was 14 months for complete responders . Two patients ( 15.4 % ) are alive with no evidence of disease at 41 and 59 months . Seven of 13 patients experienced a hematologic toxicity ( six grade 2 , one grade 3 ) ; all resolved within 2 weeks . Dose reduction of carboplatin to 200 mg/m2 was required in one patient . No other toxicities were encountered . The median survival for all patients is 11 months , and is 33 months for complete responders . We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer PURPOSE Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma . Based on encouraging response rates in breast cancer with high-dose megestrol acetate ( MA ) 800 mg/d , this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA .  PATIENTS AND METHODS Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group ( GOG ) study . Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy .  MA 800 mg/d was administered orally in divided 
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Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies .
Conclusion : Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low .