***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: BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer AIM --To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content ( oestrogen receptor index ) and proliferative activity ( MIB-1 index ) in breast cancer . METHODS --Two monoclonal antibodies , MIB-1 and oestrogen receptor , were applied to  formalin fixed , paraffin wax embedded tissue from 25 prospect ively collected oestrogen receptor positive breast carcinomas , using a microwave antigen retrieval method . Tumour tissue was allocated systematic ally to different periods of fixation to ensure minimal intraspecimen variation . The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sample d systematic ally from the entire specimen and from the whole tumour area of one " representative " cross-section . RESULTS --No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation . The estimated MIB-1 and oestrogen receptor indices in tissue sample d systematic ally from the entire tumour were closely correlated with estimates obtained in a " representative " section . The intra- and interobserver correlation of the MIB-1 index was good , although a slight systematic al error at the second assessment of the intraobserver study was noted . CONCLUSION --Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin , varying from less than four hours to more than 48 hours . The MIB-1 and the oestrogen receptor indices obtained in a " representative " section do not deviate significantly from average indices determined in tissue sample s from the entire tumour . Finally , the estimation of MIB-1 index is reproducible , justifying its routine use OBJECTIVE To evaluate prospect ively the degree of correlation between immunocytochemical ( ICC ) and immunohistochemical ( IHC ) determination of estrogen ( ER ) and progesterone receptors ( PR ) in breast cancer . STUDY DESIGN  Fine needle aspiration cytology ( FNAC ) of 101 primary breast cancers were immunostained for ER and PR . They were compared with similar determinations in formalin-fixed paraffin sections of biopsies from the same patients . In cases of discrepancy , the histologic result was considered the gold st and ard . RESULTS For ER a cytohistologic correlation of 94 % , with a sensitivity of 96.1 % and specificity of 86.9 % , was found . For PR the cytohistologic correlation was 71.2 % , with a sensitivity of 65.7 % and specificity of 83.8 % . CONCLUSION ICC determination of hormone receptors in routinely fixed smears obtained by FNAC is a simple method that correlates adequately with the results of IHC determinations , especially for ER Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment . We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy . Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6 ; treatment order was r and omly assigned . Pretreatment core biopsy sample s were interrogated for genes that might correlate with pathologic complete response ( pCR ) . In addition to the individual genes , the correlation of the Oncotype DX Recurrence Score with pCR was examined . Results Of 70 patients enrolled in the parent trial , core biopsies sample s with sufficient RNA for gene analyses were available from 45 patients ; 9 ( 20 % ) had inflammatory breast cancer ( IBC ) . Six ( 14 % ) patients achieved a pCR . Twenty-two of the 274 c and i date genes assessed correlated with pCR ( p < 0.05 ) . Genes correlating with pCR could be grouped into three large clusters : angiogenesis-related genes , proliferation related genes , and invasion-related genes . Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR . In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer ; twenty-four ( 9 % ) of the genes were differentially expressed ( p < 0.05 ) , 5 were upregulated and 19 were downregulated in IBC . Conclusion Gene expression analysis on core biopsy sample s is feasible and identifies c and i date genes that correlate with pCR to primary chemotherapy . Gene expression in IBC differs significantly from noninflammatory breast cancer The  21‐gene recurrence score ( RS ) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)‐positive , lymph node (LN)‐negative breast cancer who are treated with tamoxifen . To the authors ' knowledge , the association between the RS and clinicopathologic characteristics has been studied in r and omized and case‐control trials , but not in the general population PURPOSE To develop a guideline to improve the accuracy of immunohistochemical ( IHC ) estrogen receptor ( ER ) and progesterone receptor ( PgR ) testing in breast cancer and the utility of these receptors as predictive markers . METHODS The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance . RESULTS Up to 20 % of current IHC determinations of ER and PgR testing worldwide may be inaccurate ( false negative or false positive ) . Most of the issues with testing have occurred because of variation in preanalytic variables , thresholds for positivity , and interpretation criteria . RECOMMENDATIONS The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences . A testing algorithm that relies on accurate , reproducible assay performance is proposed . Elements to reliably reduce assay variation are specified . It is recommended that ER and PgR assays be considered positive if there are at least 1 % positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal ( normal epithelial elements ) and external controls . The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of r and omized clinical trials Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays . However , most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor , but unfortunately no vali date d immunohistochemical assay exists for progesterone receptor . The purpose of this study was to develop and vali date an immunohistochemical assay for progesterone receptor in breast cancer . The assay was based on monoclonal antibody 1294 ( DakoCytomation ) and slides were scored microscopically using the ‘ Allred score ’ on a scale of 0–8 . The assay was compared to lig and -binding assay in 1235 breast cancers , and a subset ( n=362 ) that received only hormonal therapy was used to define a cutoff for progesterone receptor-positive . Clinical utility was vali date d in an independent set of sample s ( n=423 ) from a clinical trial r and omizing premenopausal breast cancer patients to tamoxifen+oophorectomy vs observation following surgery .  A cutoff of > 2 ( corresponding to > 1 % positive cells ) dichotomized patients with significantly better or worse clinical outcome ( P=0.0014 ) . Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by lig and -binding assay in predicting clinical outcome . In the clinical trial , a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated ( hazard ratios/P=0.656/0.060 and 0.479/0.005 , respectively ) and hormonally treated patients ( hazard ratios/P=0.529/0.017 and 0.451/0.007 , respectively ) . Positive progesterone receptor remained significant for improved disease-free and overall survival ( hazard ratios/P=0.666/0.038 and 0.549/0.007 , respectively ) in multivariate analyses including the st and ard variables of tumor size , nodal status , treatment , histological grade , and HER-2/neu status . Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis . This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer . Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by lig and -binding assay Purpose : Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor – positive breast cancer , and it still remains important due to its well-documented beneficial effect . Hormone receptor status is often reported as “ positive ” or “ negative ” using 10 % positive nuclei as a cutoff . In this study , we aim ed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value . Experimental Design : The immunohistochemical expression of estrogen receptor ( ER ) and progesterone receptor ( PR ) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a r and omized trial of adjuvant tamoxifen compared with an untreated control group .  Results : Our findings show a gradually increasing tamoxifen effect in tumors with > 10 % ER-positive nuclei . However , when analyzing  tamoxifen response according to various PR fractions , we found that it was primarily patients with tumors showing > 75 % PR-positive nuclei that responded to tamoxifen treatment , with an improved recurrence-free [ relative risk , 0.42 ( 0.25 - 0.70 ) ; P = 0.001 ] as well as overall [ relative risk , 0.49 ( 0.28 - 0.84 ) ; P = 0.010 ] survival . Conclusions : Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing > 75 % PR-positive nuclei . No effect could be shown in tumors with fewer PR-positive nuclei . The PR was a stronger predictor of treatment response than the ER . Based on these findings , we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice , possibly with greater emphasis on the PR than the ER Aim : To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment . Methods : The treatment group consisted of 31 patients with operable breast carcinomas , median age 57 years ( range 41–67 ) , treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone , methotrexate ( ± mitomycin C ) , and tamoxifen before surgery . Fine needle aspiration ( FNA 
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It is anticipated that widespread adoption of these guidelines will further improve the accuracy of hormone receptor testing in Canada