***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 
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    ***EXAMPLES*** 
    Input: Estrogens administered in high doses were commonly used for therapy of advanced breast cancer before the introduction of contemporary endocrine therapy . While the mechanism of the antitumor effect is unknown , in vitro investigations have shown estrogens in high concentrations to be toxic to cell growth . Further , it has been shown that exposure of MCF-7 cells to estrogens in low concentrations may enhance the sensitivity and also lower the toxicity threshold to estrogens . This study was design ed to evaluate treatment with diethylstilbestrol ( DES ) in postmenopausal women with advanced breast cancer becoming resistant to estrogen deprivation . Thirty-two patients with advanced breast cancer previously exposed to multiple endocrine treatment regimens ( median 4 , range 2–10 ) were enrolled . Their tumor should have revealed evidence of endocrine sensitivity ( previous partial response or at least stable disease for ≥6 months to therapy ) . Each patient received DES 5 mg t.i.d . Four patients terminated therapy after ≤2 weeks on therapy due to side effects ; another two patients terminated therapy before progression for similar reasons ( one patient after SD for 15 weeks and one with a PR after 39 weeks ) . Four patients obtained CR and six patients PR . In addition , two patients had SD for ≥6 months duration . Five patients had an objective response and one patient a SD lasting for ≥1 year . Our results reveal estrogens administered in high doses may have antitumor effects in breast cancer patients heavily pretreated with endocrine therapy . Such treatment represents a valuable alternative to chemotherapy in selected patients It was previously shown that letrozole ( Femara ) was significantly more potent than anastrozole ( Arimidex ) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer . The objective of this study was to compare letrozole ( 2.5 mg per day ) and anastrozole ( 1 mg per day ) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen . This r and omised , multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients . Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy . Patients had tumours that were either positive for oestrogen and /or progesterone receptors ( 48 % ) or of unknown receptor status ( 52 % ) . The primary efficacy endpoint was time to progression ( TTP ) . Secondary endpoints included objective response , duration of response , rate and duration of overall clinical benefit ( responses and long-term stable disease ) , time to treatment failure , and overall survival , as well as general safety . There was no difference between the treatment arms in TTP ; median times were the same for both treatments . Letrozole was significantly superior to anastrozole in the overall response rate ( ORR ) ( 19.1 % versus 12.3 % , P=0.013 ) , including in predefined subgroups ( receptor status-unknown , and soft-tissue- and viscera-dominant site of disease ) . There were no significant differences between the treatment arms in the rate of clinical benefit , median duration of response , duration of clinical benefit , time to treatment failure or overall survival . Both agents were well tolerated and there were no significant differences in safety . These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy Abstract Purpose . This retrospective evaluation of data from two r and omized , multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy , usually tamoxifen , and on the estrogen receptor ( ER ) antagonist fulvestrant ( ' Faslodex ' ) . Patients and methods . A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection . After progression on fulvestrant , some patients received another endocrine therapy . Responses to subsequent endocrine therapy were assessed using a question naire sent to the trial investigators . Best responses were classified as a complete or partial response ( CR or PR ) , stable disease ( SD ) lasting ≥24 weeks , or disease progression . Results . Follow-up data were available for 54 patients who derived clinical benefit ( CB , defined as CR , PR or SD ) from fulvestrant and who received subsequent endocrine therapy  , result ing in a PR in 4 patients , SD in 21 patients , and disease progression in 29 patients . Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy , result ing in a PR in 1 patient , SD in 17 patients , and disease progression in 33 patients . Aromatase inhibitors were used as subsequent endocrine therapy in > 80 % of patients . Conclusions . After progression on fulvestrant , patients may retain sensitivity to other endocrine agents . Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women , and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required Fulvestrant ( ICI 182,780 ) is a new type of estrogen receptor ( ER ) antagonist that down‐regulates the ER and has no known agonist effects . The authors report the prospect ively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly ( n = 428 ) and anastrozole 1 mg daily ( n = 423 ) in postmenopausal women with advanced breast carcinoma ( ABC ) who previously had progressed after receiving endocrine treatment PURPOSE To compare two doses of letrozole ( 0.5 mg and 2.5 mg every day ) and megestrol acetate ( 40 mg qid ) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens . PATIENTS AND METHODS This double-blind , r and omized , multicenter , multinational study enrolled 602 patients , all of whom were included in the primary analysis in the protocol . Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy , had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months , or had experienced disease progression while receiving antiestrogen therapy for advanced disease . Tumors were required to be estrogen receptor- and /or progesterone receptor-positive or of unknown status . Confirmed objective response rate was the primary efficacy variable . Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality -of-life assessment s were collected for 1 year . RESULTS There were no statistically significant differences among the three treatment groups for overall objective tumor response . Patients treated with letrozole 0.5 mg had improvements in disease progression ( P = .044 ) and a decreased risk of treatment failure ( P = .018 ) , compared with patients treated with megestrol acetate . Letrozole 0.5 mg showed a trend ( P = .053 ) for survival benefit when compared with megestrol acetate . Megestrol acetate was more likely to produce weight gain , dyspnea , and vaginal bleeding , and the letrozole groups were more likely to experience headache , hair thinning , and diarrhea . CONCLUSION Given a favorable tolerability profile , once-daily dosing , and evidence of clinical ly relevant benefit , letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens Fulvestrant is an estrogen receptor antagonist with no agonist effects . In the second‐line treatment of advanced breast carcinoma , fulvestrant was shown previously to be as effective as the third‐generation aromatase inhibitor , anastrozole , in terms of time to disease progression and objective response rates . The authors reported the overall survival results from these studies PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in pre clinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were r and omized to 21-day cycles of oral capecitabine 1,250 mg/m(2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m(2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel result ed in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P = .0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P = .0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P = .006 ) compared with docetaxel .  Gastrointestinal side effects and h and -foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC PURPOSE Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen . This study was design ed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor ( AI ) .  PATIENTS AND METHODS A one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and , at most , one additional hormonal agent .  Tumors must have been estrogen receptor and /or progesterone receptor positive . The primary end point was objective response rate , and secondary end points were time to disease progression , survival , duration of response , and toxicity . RESULTS Eighty patients were enrolled , and three were ineligible . Characteristics of the 77 eligible patients included median age of 68 years , performance score of 0 or 1 in 91 % of patients , visceral dominant disease in 88 % of patients , two prior hormonal treatments in 73 % of patients , and prior chemotherapy for metastatic disease in 32 % of patients . Eleven patients ( 14.3 % ) achieved a partial response , and 16 patients ( 20.8 % ) had stable disease for at least 6 months , for a clinical benefit rate of 35 % . Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen . Median time to progression was 3 months , and median survival time was 20.2 months . Fulvestrant was well tolerated . CONCLUSION Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI PURPOSE To compare the efficacy and tolerability of fulvestrant ( formerly ICI 182,780 ) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment . PATIENTS AND METHODS In this double-blind , double-dummy , parallel-group study , postmenopausal patients were r and omized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg . The primary end point was time to progression ( TTP ) . Secondary end points included objective response ( OR ) rate , duration of response ( DOR ) , and tolerability . RESULTS Patients ( n = 400 ) were followed for a median period of 16.8 months . Fulvestrant was as effective as anastrozole in terms of TTP ( hazard ratio , 0.92 ; 95.14 % confidence interval [ CI ] , 0.74 to 1.14 ; P = .43 ) ; median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole . OR rates were 17.5 % with both treatments . Clinical benefit rates ( complete response + partial response + stable disease > or = 24 weeks ) were 42.2 % for fulvestrant and 36.1 % for anastrozole ( 95 % CI , -4.00 % to 16.41 % ; P = .26 ) . In responding patients , median DOR ( from r and omization to progression ) was 19.0 months for fulvest 
    Output:
    
Sensitivity analyses showed these results to be robust , demonstrating that fulvestrant is an economically viable additional endocrine option in the United Kingdom for the treatment of hormone responsive advanced breast cancer