***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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    Input: Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy , although the incidence of local recurrences was higher . Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery . We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases , refuse surgery or are of old age . Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery , were judged ineligible for surgery because of comorbidity , or were of old age were treated with endocrine therapy using aromatase inhibitors only . Digital mammography and high-end breast ultrasound were used to assess tumor sizes . The mean age of the patients was 74 years ( range 52 - 102 years ) . All patients suffered from breast cancer . The mean follow-up interval was 40 months ( range 5 - 92 months ) . Seven patients ( 12 % ) achieved complete clinical remission , 31 ( 57 % ) partial response giving an overall objective response rate of 69 % . In addition , seven ( 12 % ) patients showed stable disease , giving a clinical benefit rate ( complete remission + partial response + stable disease rate ) of 81 % . Eleven patients ( 19 % ) progressed after an initial partial response or stable disease . Only one patient ( 2 % ) progressed on endocrine therapy within the first months . Eventually , 22 ( 39 % ) patients underwent surgery after informed consent to achieve better local tumor control .  Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery , who are judged ineligible for surgery , or are of old age Invasive lobular cancer ( ILC ) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy . We examined the effectiveness of neoadjuvant letrozole in postmenopausal women ( PMW ) with estrogen receptor (ER)-rich ILC . PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich , large operable , or locally advanced cancers , or were unfit for surgical therapy . Tumor volume was estimated at diagnosis and at 3 months using calipers ( clinical ) , ultrasound , and mammography . At 3 months , if physically fit , women were assessed for surgery . Responsive women with cancers too large for breast-conserving surgery continued with letrozole . Patients had surgery or were switched to alternative therapy if tumor volume was increasing . Sixty-one patients ( mean age , 76.2 years ) with 63 ILCs were treated with letrozole for ≥3 months . The mean reduction in tumor volume at 3 months was 66 % ( median , 76 % ) measured clinical ly , 61 % ( median , 73 % ) measured by ultrasound , and 54 % ( median , 60 % ) measured by mammography . Surgery was possible at 3 months in 24 cancers in 24 patients , and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months . At the time of this publication , 40 patients with a total of 41 cancers have undergone surgery . The rate of successful breast conservation was 81 % ( 25/31 ) . Twenty-one patients have continued with letrozole monotherapy , and 19 remain controlled on letrozole at a median of 2.8 years . There is a high rate of response to letrozole in PMW with ER-rich ILC Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter ( T2 , T3 , N0 , N1 , M0 ) have received primary systemic therapy .  Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume . Definitive locoregional surgery ( mastectomy n = 82 , wide local excision n = 6 ) was performed on completion of systemic therapy ( 3 - 6 months ) . Response was observed in 24 ( 39 % ) of the 61 patients who received endocrine therapy ;  all 24 had tumours with an oestrogen receptor ( ER ) concentration of greater than or equal to 20 fmol mb-1 cytosol protein . Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein ( n = 27 ) or when endocrine therapy had failed ( n = 20 ) . Response was observed in 34 patients ( 72 % ) . The overall survival rate at 3 years was 86 % , with 81 % remaining free from local relapse . We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled r and omised trial Background In recent years , preoperative volume reduction of locally advanced breast cancers , result ing in higher rates of breast-conserving surgery ( BCS ) , has become increasingly important also in postmenopausal women . Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors ( AIs ) , including letrozole , for such neoadjuvant endocrine treatment . This usually lasts 3–4 months and has been extended to up to 12 months , but optimal treatment duration has not been fully established . Methods This study was design ed as a multicenter , open-label , single-arm , exploratory phase IIb/III clinical trial of letrozole 2.5 mg , one tablet daily , for 4–8 months . The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration . Tumor regression ( by clinical examination , mammography , and ultrasound ) , shift towards BCS eligibility , and safety assessment s were the main outcome measures . St and ard parametric and nonparametric descriptive statistics were performed . Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women ( median ( range ) : 67.0 ( 56–85 ) years ) with unilateral , initially BCS-ineligible primary breast cancer ( clinical stage ≥ T2 , N0 , M0 ) . Letrozole treatment duration in the modified intent-to-treat ( ITT ; required 4 months ' letrozole treatment ) analysis population ( 29 patients ) was 4 months in 14 patients and > 4 months in 15 patients . The respective per- protocol ( PP ) subgroup sizes were 14 and 11 . The majority of partial or complete responses were observed at 4 months , though some beneficial responses occurred during prolonged letrozole treatment . Compared with baseline , median tumor size in the ITT population was reduced by 62.5 % at Month 4 and by 70.0 % at final study visit ( Individual End ) . Similarly , in the PP population , respective reductions were 64.0 % and 67.0 % . Whereas initially all patients were mastectomy c and i date s , letrozole treatment enabled BCS ( lumpectomy ) in 22 ITT ( 75.9 % ) and 18 PP ( 72.0 % ) patients . Conclusion Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment . While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients , there is no clear optimum for treatment duration . Letrozole has a favorable overall safety and tolerability profile . Trial registration Clinical Trials.gov identifier NCT00535418 BACKGROUND Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer . A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice . STUDY DESIGN One hundred fifteen postmenopausal women with > 2 cm , estrogen receptor ( ER ) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation . RESULTS One hundred six patients were eligible for primary analysis , 96 underwent  operations  , 7 received chemotherapy after progressive disease , and 3 did not undergo an operation . Baseline surgical status was marginal for breast-conserving surgery ( BCS ) in 48 ( 45 % ) , 47 were definitely ineligible for BCS ( 44 % ) , and 11 were inoperable by st and ard mastectomy ( 10 % ) . Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62 % , with 12 % experiencing progressive disease . Fifty percent underwent BCS , including 30 of 46 ( 65 % ) patients who were initially marginal for BCS and 15 of 39 ( 38 % ) patients who were initially ineligible for BCS . All 11 inoperable patients successfully underwent operations , including 3 ( 27 % ) who had BCS . Nineteen percent of patients undergoing mastectomy had a pathologic T1 tumor , suggesting that some highly responsive tumors were overtreated surgically . CONCLUSIONS Neoadjuvant aromatase inhibitor  improves operability and facilitates BCS , but there was considerable variability in responsiveness . Better techniques to predict response , determine residual tumor burden before operation , and greater willingness to attempt BCS in responsive patients could additionally improve the rate of successful BCS It has been proposed that knowledge of estrogen receptor beta ( ER-beta ) expression may refine estrogen receptor alpha ( ER-alpha ) predictivity of response to endocrine therapy . We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment . Forty-seven elderly ( > or = 65 years old ) women with nonmetastatic , ER-alpha-positive ( by immunohistochemistry ) primary breast cancers ( > 2 cm in diameter ) entered a neoadjuvant hormone therapy protocol ( 60 mg/day toremifene for 3 months ) . ER-alpha and ER-beta ( ERs ) mRNA was determined by semiquantitative RT-PCR , before ( on core needle biopsy ) and after ( on surgical specimens ) neoadjuvant treatment . Study end points included : ( 1 ) relation between treatment response and ER mRNA expression ; and ( 2 ) changes in ER expression after treatment . The response was clinical ly assessed as tumor size change at the end of the preoperative treatment . ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively . ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor ( P = 0.0285 ) . Objective clinical response , including patients with minor change ( > or = 25-<50 % tumor shrinkage after treatment ) , was documented in 68.4 % of cases and was independent of ER-beta levels or changes . ER-alpha levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients ( median expression values : 801 versus 516 versus 320 arbitrary units ) and were consistently down-regulated by preoperative treatment . We conclude that in this elderly patient population with ER-alpha-positive tumors , ER-beta mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-alpha mRNA levels , which , conversely , were directly correlated with likelihood of response OBJECTIVES To evaluate the efficacy and safety of combing aromatase inhibitor ( AI ) and cyclooxygenase-2 ( COX-2 ) inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer . METHODS Eighty-two patients were r and omly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice daily ( group A , n=30 ) , exemestane 25 mg daily ( group B , n=24 ) and letrozole 2.5 mg daily ( group C , n=28 ) . RESULTS All groups showed clinical responses ( 58.6 % for group A , 54.5 % for group B and 62.0 % for group C ) and decrease in tumor area ( 61.8 % for group A , 58.1 % for group B and 55.7 % for group C ) . 3 out of 5 patients with complete clinical response were observed from group A and 2 out of 69 patients operated with pathologic complete response were observed in group C. The mean microscopic tumor size was 2.53 cm for group A , 3.05 cm for group B and 2.10 cm for group C. The differences were only statistically significant when group C was compared with group B ( P=0.025 ) . The toxicity profiles among groups were satisfactory . CONCLUSION AI is effective in treating breast cancer and may be safely used preoperatively . The addition of COX-2 inhibitor may provide additional benefit In 1973 , the European Institute of Oncology performed the first prospect i ve neoadjuvant chemotherapy study in locally advanced , inoperable breast cancer . The original purpose was to downstage the primary tumor in order to achieve surgical resection . This approach has subsequently increased in popularity , and in the last 10 years , r and omized controlled trials of neoadjuvant chemotherapy have been performed with a view to further downstage the primary tumor and lymph nodes in order to achieve greater rates of breast-conserving surgery and to test whether systemic therapy given earlier would confer a survival benefit . Although the net result of these trials did demonstrate 
    Output:
    
In studies comparing tamoxifen with aromatase inhibitors , the latter were superior in terms of tumor response and rates of breast-conserving surgery ( BCS ) .