***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: BACKGROUND Some oestrogen-receptor ( ER ) positive breast cancers express epidermal growth factor receptor ( EGFR ) , but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known . METHODS In a double-blind , placebo-controlled r and omised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer , 27 women were r and omly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib ( 250 mg given orally once a day ) and the aromatase inhibitor anastrozole ( 1 mg given orally once a day ) , and 29 women to gefitinib ( 250 mg given orally once a day ) and placebo of identical appearance to anastrozole given orally once a day , all given for 4 - 6 weeks before surgery . Primary outcome was inhibition of tumour-cell proliferation , as measured by Ki67 antigen labelling index . Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845 , reduction in ER phosphorylation at Ser 118 , tumour size , and toxic effects . Analyses were by intention to treat . FINDINGS Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone ( mean % reduction 98.0 [ 95 % CI 96.1 - 98.9 ] vs 92.4 [ 85.1 - 96.1 ] ; difference between groups 5.6 % [ 5.1 - 6.0 ] , p=0.0054 ) . Tumour size was reduced by 30 - 99 % ( partial response ) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib , as assessed by ultrasonography . Reduction in phosphorylation of ER at Ser 118 was similar for both groups . Treatment was well tolerated and much the same for both groups . INTERPRETATION Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy Endocrine therapy in patients with breast cancer can be limited by the problem of resistance . Pre clinical studies suggest that complete blockade of the estrogen receptor ( ER ) combined with inhibition of the epidermal growth factor receptor can overcome endocrine resistance . We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer . After a baseline tumor core biopsy , patients were r and omized to receive anastrozole and fulvestrant or anastrozole , fulvestrant , and gefitinib ( AFG ) for 3 weeks . After a second biopsy at 3 weeks , all patients received AFG for 4 months and surgery was done if the tumor was operable . The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers . The study closed after 15 patients were enrolled because of slow accrual . Median patient age was 67 years and median clinical tumor size was 7 cm . Four patients had metastatic disease present . Three patients withdrew before response was assessed . In the remaining 12 patients , there were two complete clinical responses ( 17 % ) , three partial responses ( 25 % ) , five had stable disease ( 41 % ) , and two ( 17 % ) had progressive disease . Most common adverse events were rash in four patients , diarrhea in four , joint symptoms in three , and abnormal liver function tests in three . There were no grade 4 toxicities and all toxicities were reversible . At 3 weeks , cell proliferation as measured by Ki-67 was significantly reduced in the AFG group ( P value = 0.01 ) , with a parallel reduction in the expression of the Cyclin D1 ( P value = 0.02 ) . RNA microarray data showed a corresponding decrease in the expression of cell cycle genes . These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors PURPOSE This study was design ed to determine the effect of adding docetaxel ( T ) to preoperative doxorubicin and cyclophosphamide ( AC ) on  breast cancer response rates and disease-free survival ( DFS ) and overall survival ( OS ) . PATIENTS AND METHODS Women with operable breast cancer ( N = 2,411 ) were r and omly assigned to receive preoperative AC followed by surgery , AC followed by T and surgery , or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy . Median time on study for 2,404 patients with follow-up was 77.9 months . RESULTS Addition of T to AC did not significantly impact DFS or OS . There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events ( P = .0034 ) . Preoperative T , but not postoperative T , significantly improved DFS in patients who had a clinical partial response after AC ( hazard ratio [ HR ] = 0.71 ; 95 % CI , 0.55 to 0.91 ; P = .007 ) . Pathologic complete response , which was doubled by addition of preoperative T , was a significant predictor of OS regardless of treatment ( HR = 0.33 ; 95 % CI , 0.23 to 0.47 ; P < .0001 ) . Pathologic nodal status after chemotherapy was a significant predictor of OS ( P < .0001 ) . CONCLUSION The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS , slightly improved DFS , and decreased the incidence of local recurrences . The sample size of this study was not sufficient to yield significance for the moderate DFS improvement . Concurrent use of tamoxifen may have limited the impact of adding INTRODUCTION Tumor content or expression of vascular endothelial growth factor ( VEGF ) is associated with impaired efficacy of antiestrogen adjuvant therapy . We design ed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab ( anti-VEGF ) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer . PATIENTS AND METHODS Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer . Patients were followed for toxicity at 3-week intervals , and tumor assessment ( a physical examination and ultrasound ) was performed at 6-week intervals . Positron emission tomography ( PET ) scans were performed before therapy and 6 weeks after the initiation of therapy . RESULTS Twenty-five evaluable patients were treated . The regimen was well-tolerated , except in 2 patients who were taken off the study for difficulties controlling their hypertension . An objective clinical response occurred in 17 of 25 patients ( 68 % ) , including 16 % complete responses ( CRs ) and 52 % partial responses . The 4 patients with clinical CRs manifested pathologic CRs in their breasts ( 16 % ) , although 1 patient had residual tumor cells in her axillary nodes . Eight of 25 patients ( 32 % ) attained stage 0 or 1 status . The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks ( P < .0036 ) . CONCLUSION Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and result ed in impressive clinical and pathologic responses . The Translational Breast Cancer Research Consortium has an ongoing r and omized phase II trial of this regimen in this patient population Background : The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response ( pathCR ) and assess Ki-67 expression as an early predictor of response . Patients and methods : This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer ( clinical stage ⩾T2 , N0–1 ) , from three sequential cohorts ( cohort A of 40 , cohort B of 40 and cohort C of 40 patients , respectively ) based on different duration of the neoadjuvant letrozole .  Biological markers such as ER , progesterone receptor , HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery . Results : A total of 89 patients ( 75.4 % ) achieved an objective response with 44 ( 37.3 % ) clinical CRs and 45 ( 38.1 % ) partial responses . The clinical CRs were significantly observed in cohort C ( 23 out of 40 patients , 57.5 % ) and B ( 16 out of 38 patients , 42.1 % ) compared with cohort A ( 5 out of 40 patients , 12.5 % ) ( P-value for trend < 0.001 ) . Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts . The pathCR rate was significantly more frequent in cohort C ( 7 out of 40 patients , 17.5 % ) than in cohort A ( 1 out of 40 patients , 2.5 % ) and B ( 2 out of 40 patients , 5.0 % ) ( P-value for trend < 0.04 ) . Conclusion : One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure PURPOSE To assess patient and tumor characteristics associated with a complete pathologic response ( pCR ) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Three hundred seventy-two LABC patients received treatment in two prospect i ve neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy .  Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy .  Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics . Median follow-up was 58 months ( range , 8 to 99 months ) . RESULTS The initial nodal status , age , and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR ( P>.05 ) . Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative ( P<.01 ) , and anaplastic ( P = .01 ) but of smaller size ( P<.01 ) than those of patients with less than a pCR . Upon multivariate analysis , the effects of ER status and nuclear grade were independent of initial tumor size . Sixteen percent of the patients in this study ( n = 60 ) had a pathologic complete primary tumor response . Twelve percent of patients ( n = 43 ) had no microscopic evidence of invasive cancer in their breast and axillary specimens . A pathologic complete primary tumor response was predictive of a complete axillary lymph node response ( P<.01 ) . The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR ( 89 % and 87 % , respectively ) than in the group who had less than a pCR ( 64 % and 58 % , respectively ; P<.01 ) . CONCLUSION Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery . Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate . However , a pCR does not entirely eliminate recurrence . Further efforts should focus on elucidating the molecular mechanisms associated with this response A panel of international breast cancer experts formulated a declaration of consensus regarding many key issues in the use of primary systemic therapy ( PST ) either in clinical routine or research practice . The attainment of pathological complete response ( pCR ) , defined as no residual invasive tumor in the surgical specimens both in breast and in axillary nodes , is one of the main goals of PST , and pCR can be used as the primary objective in prospect i ve clinical trials . However , pCR is not a reliable endpoint with all treatment approaches , and alternatives such as Ki67 index of the residual invasive disease or after 2 weeks of PST are also potential endpoints . PST has several advantages : breast conservation and the unique opportunity to obtain information on the interaction between treatment and tumor biology . Changes in tumor biology after PST are an early phenomenon ; so , an additional core biopsy performed after 14 days from treatment start should be considered in clinical trials PURPOSE Within breast tissue , aromatase expression and activity is increased by prostagl and in E2 , providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor . To evaluate the effect of these drugs on aromatase and other biomarkers , a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed . METHODS Postmenopausal women with estrogen receptor ( ER ) and /or progesterone ( PR ) positive stages II 
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Overall the studies failed to show a remarkable advantage in RR in the combination group compared to historical control subjects receiving AIs alone