Economic Analysis of Gene Expression Profile Data to Guide Adjuvant Treatment in Women with Early-Stage Breast Cancer Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting A study of the impact of the 21-gene breast cancer assay on the use of adjuvant chemotherapy in women with breast cancer in a Mexican public hospital. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study. Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. Impact of a 21‐gene RT‐PCR assay on treatment decisions in early‐stage breast cancer Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. A prospective clinical utility and pharmacoeconomic study of the impact of the 21-gene Recurrence Score® assay in oestrogen receptor positive node negative breast cancer. The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use The impact of the 21-gene assay on adjuvant treatment decisions in oestrogen receptor-positive early breast cancer: a prospective study Trial assessing individualized options for treatment for breast cancer: the TAILORx trial. The impact of the pathological lymph node status on adjuvant systemic treatment recommendations in clinically node negative breast cancer patients Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. Decisional Support throughout the Cancer Journey for Older Women Diagnosed with Early Stage Breast Cancer: A Single Institutional Study Impact of Oncotype DX Recurrence Score on Treatment Decisions: Results of a Prospective Multicenter Study in Turkey SWOG S1007: A phase III, randomized clinical trial of standard adjuvant endocrine therapy with or without chemotherapy in patients with one to three positive nodes, hormone receptor (HR)-positive, and HER2-negative breast cancer with recurrence score (RS) of 25 or less. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
Breast cancer is the second most common type of cancer among women in the United States with more than 200,000 women diagnosed with invasive disease and with approximately 40,000 dying annually from the disease ( 1 ) . As a result of early detection efforts , nearly half of these women present with lymph node negative hormone receptor positive disease . Current treatment for early-stage breast cancer ( ESBC ) with adjuvant hormonal therapy and /or chemotherapy is based on clinical and pathological criteria including the presence and number of involved lymph nodes , tumor size and grade , hormone receptor status , and the presence of HER2/neu overexpression among others . Treatment decisions may also take into consideration patient age or menopausal status due to the anticipated lower risk of cancer recurrence , and the potential for smaller benefit and greater toxicity with aggressive systemic chemotherapy in older women . These considerations form the basis for clinical practice guidelines for the management of patients with ESBC ( 2 , 3 ) . Current guidelines recommend adjuvant systemic chemotherapy and endocrine therapy for most women with lymph node negative , hormone receptor positive , ESBC . Unfortunately , such systemic chemotherapy is associated with considerable cost , proximal morbidity , as well as increasing evidence for serious delayed toxicities including neurocognitive dysfunction and secondary malignancies . The risk of distant recurrence is generally low among ESBC patients with lymph node negative , hormone receptor positive disease regardless of treatment with adjuvant chemotherapy . However , several r and omized controlled trials of adjuvant chemotherapy and meta-analyses have shown the value of adjuvant chemotherapy in reducing the risk of disease Abstract Objective : The 21-gene assay ( Oncotype DX Breast Cancer Test ( Genomic Health Inc. , Redwood City , CA ) ) is a well vali date d test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+ , HER2− early-stage breast cancer . The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany . Methods : A Markov model was developed to make long-term projections of distant recurrence , survival , quality -adjusted life expectancy , and direct costs for patients with ER+ , HER2− , node-negative , or up to 3 node-positive early-stage breast cancer . Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospect i ve , multi-center trial in 366 patients . Transition probabilities and risk adjustment were based on published l and mark trials . Costs ( 2011 Euros ( € ) ) were estimated from a sick fund perspective based on re source use in patients receiving chemotherapy . Future costs and clinical benefits were discounted at 3 % annually . Results : The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality -adjusted life expectancy by 0.06 quality -adjusted life years ( QALYs ) compared with current clinical practice over a 30-year time horizon . Clinical benefits were driven by optimized allocation of adjuvant chemotherapy . Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs st and ard of care . Probabilistic sensitivity analysis indicated that there was an 87 % probability that the 21-gene assay would be dominant ( cost and life saving ) to st and ard of care . Limitations : Country-specific data on the risk of distant recurrence and quality -of-life were not available . Conclusions : Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival , quality -adjusted life expectancy , and be cost saving vs the current st and ard of care women with ER+ , HER2− early-stage breast cancer BACKGROUND The majority of breast cancer patients in Mexico are treated through the public health system and > 80 % receive adjuvant chemotherapy . The aim of this prospect i ve study was to characterize the impact of the Oncotype DX assay on adjuvant therapy decision making and the confidence in those decisions amongst public sector physicians in Mexico . METHODS Ninety-eight consecutive patients with ER+ , HER2- , stage I-IIIa , N0/N1 - 3 node-positive breast cancer from the Instituto Nacional de Cancerología were eligible for the study . The primary endpoint was the overall change in treatment recommendations after receiving the assay results . RESULTS Of 96 patients , 48 % received a  chemohormonal therapy recommendation  prior to testing . Following receipt of results , treatment decisions changed for 31/96 ( 32 % ) patients , including 17/62 ( 27 % ) node-negative patients and 14/34 ( 41 % ) node-positive patients . The proportion of patients with a chemotherapy-based recommendation decreased from 48 % pre- to 34 % post-assay ( P=0.024 ) . 92 % of physicians agreed that they were more confident in their treatment recommendation after ordering the assay . CONCLUSIONS These results suggest that use of the 21-gene assay in the Mexican public health system has a meaningful impact on adjuvant treatment recommendations that may reduce the overall use of chemotherapy Abstract Purpose : Improved underst and ing of risk of recurrence ( ROR ) is needed to reduce cases of recurrence and more effectively treat breast cancer patients . The purpose of this study was to examine how a gene-expression profile ( GEP ) , identified by Prosigna , influences physician adjuvant treatment selection for early breast cancer ( EBC ) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice . Methods : A prospect i ve , observational , multicenter study was carried out in 15 hospitals across Spain . Participating medical oncologists completed pre- assessment , post- assessment , and follow-up question naires recording their treatment recommendations and confidence in these recommendations , before and after knowing the patient ’s ROR . Patients completed question naires on decision-making , anxiety , and health status . Results : Between June 2013 and January 2014 , 217 patients enrolled and a final 200 were included in the study . Patients were postmenopausal , estrogen receptor positive , human epidermal growth hormone factor negative , and node negative with either stage 1 or stage 2 tumors . After receiving the GEP results , treatment recommendations were changed for 40 patients ( 20 % ) . The confidence of medical oncologists in their treatment recommendations increased in 41.6 % and decreased in 6.5 % of total cases . Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results ( p < 0.05 ) . Conclusions : Though this study does not include evaluation of the impact of GEP on long-term outcomes , it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection . Patients ’ anxiety about the selected adjuvant therapy decreased with use of the GEP BACKGROUND The 21-gene Oncotype DX Recurrence Score assay is a vali date d assay to help decide the appropriate treatment for estrogen receptor-positive ( ER+ ) , early-stage breast cancer ( EBC ) in the adjuvant setting . The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines . This prospect i ve multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting . METHODS A total of 100 patients with ER+ , human epidermal growth factor receptor 2-negative EBC , and node-negative ( pN0 ) disease or micrometastases in up to 3 lymph nodes ( pN1mi ) were enrolled . Treatment recommendations , physicians ' confidence before and after knowing the Recurrence Score value , and physicians ' perception of the assay were recorded . RESULTS Of the 100 patients , 95 were evaluable ( 83 pN0 , 12 pN1mi ) . Treatment recommendations changed in 37 % of patients , predominantly from chemoendocrine to endocrine treatment alone . The proportion of patients recommended chemotherapy  decreased from 52 % pretest to 25 % post-test . Of patients originally recommended chemotherapy , 61 % were recommended endocrine treatment alone after receiving the Recurrence Score result . For both pN0 and pN1mi patients , post-test recommendations appeared to follow the Recurrence Score result for low and high values . Physicians ' confidence improved significantly . CONCLUSION These are the first prospect i ve data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France . Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use . These data are consistent with those presented from European and non-European studies PURPOSE A strong prognostic impact of urokinase-type plasminogen activator ( uPA ) and its inhibitor and plasminogen activator inhibitor type 1 ( PAI-1 ) as individual factors is well established in breast cancer . The improvement in clinical risk assessment gained by combining these factors is evaluated here . PATIENTS AND METHODS  uPA and PAI-1 levels  were prospect ively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer . RESULTS In the clinical ly important subgroup of node-negative patients without adjuvant systemic therapy ( n = 269 ; median follow-up , 60 months ) , the clinical value of testing both uPA and PAI-1 is demonstrated . The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group . uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival ; patients with high uPA/PAI-1 have an increased relapse risk ( P < .001 ; relative risk , 4.8 ; 95 % confidence interval [ CI ] , 2.5 to 9.1 ) , in particular for early relapse . Even within risk groups stratified by established criteria ( nodal or menopausal status , tumor size , grade , or steroid hormone receptors ) , uPA/PAI-1 provides significant risk group discrimination . In the whole collective , the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1 . CONCLUSION The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination . The particular combination of uPA and PAI-1 ( both low v either or both high ) is superior to either factor alone and supports risk-adapted individualized therapy decisions Purpose To provide current recommendations on the use of sentinel node biopsy ( SNB ) for patients with early-stage breast cancer . Methods PubMed and the Cochrane Library were search ed for r and omized controlled trials , systematic review s , meta-analyses , and clinical practice guidelines from 2012 through July 2016 . An Up date Panel review ed the identified abstract s. Results Of the eight publications identified and review ed , none prompted a change in the 2014 recommendations , which are reaffirmed by the up date d literature review . Conclusion Women without sentinel lymph node ( SLN ) metastases should not receive axillary lymph node dissection ( ALND ) . Women with one to two metastatic SLNs who are planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND ( in most cases ) . Women with SLN metastases who will undergo mastectomy should be offered ALND . These three recommendations are based on r and omized controlled trials . Women with operable breast cancer and multicentric tumors , with ductal carcinoma in situ , who will undergo mastectomy , who previously underwent breast and /or axillary surgery , or who received preoperative/neoadjuvant systemic therapy may be offered SNB .  Women who have large or locally advanced invasive breast cancer ( tumor size T3/T4 ) , inflammatory breast cancer , or ductal carcinoma in situ ( when breast-conserving surgery is planned ) or are pregnant should not undergo SNB AIM Final 10-year analysis of the prospect i ve r and omised Chemo-N0 trial is presented . Based on the Chemo-N0 interim results and an European Organisation for Research and Treatment of Cancer ( EORTC ) pooled analysis ( n=8377 ) , American Society of Clinical Oncology ( ASCO ) and Arbeitsgemeinschaft Gynäkologische Onkologie ( AGO ) guidelines recommend invasion and metastasis markers urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor-1 ( PAI-1 ) for risk assessment and treatment decision in node-negative ( N0 ) breast cancer ( BC ) . METHODS The final Chemo-N0 trial analysis ( recruitment 1993 - 1998 ; n=647 ; 12 centres ) comprises 113 ( 5 - 167 ) months of median follow-up . Patients with low-uPA and PAI-1 tumour tissue levels ( n=283 ) were observed . External quality assurance guaranteed uPA/PAI-1 enzyme-linked immunosorbent assay ( ELISA ) st and ardisation . Of 364 high uPA and /or PAI-1 patients , 242 agreed to r and omisation for CMF chemotherapy ( n=117 ) versus observation ( n=125 ) . RESULTS Actuarial 10-year recurrence rate ( without any adjuvant systemic therapy ) for high-uPA/PAI-1 observation group patients ( r and omised and non-r and omised ) was 23.0 % , in contrast to only 12.9 % for low-uPA/PAI-1 patients ( plog-rank=0.011 ) . High-risk patients r and omised to cyclophosphamide-methotrexate-5-fluorouracil ( CMF ) therapy had a 26.0 % lower estimated probability of disease recurrence than those r and omised for observation ( intention-to-treat (ITT)- analysis : hazard ratio ( HR ) 0.74 ( 0.44 - 1.27 ) ; plog-rank=0.28 ) . Per- protocol analysis demonstrated significant treatment benefit : HR 0.48 ( 0.26 - 0.88 ) , p=0.019 , disease-free survival ( DFS ) Cox regression , adjusted for tumour stage and grade . CONCLUSIONS Chemo-N0 is the first prospect i ve biomarker-based therapy trial in early BC defining patients reaching good long-term DFS without adjuvant systemic therapy . Using a st and ardised uPA/PAI-1 ELISA , almost half of N0- patients could be spared chemotherapy , while high-risk patients benefit from adjuvant chemotherapy . These 10-year results vali date the long-term prognostic impact of uPA/PAI-1 and the benefit from  adjuvant chemotherapy  in the high-uPA/PAI-1 group at highest level of evidence . They thus support the guideline -based routine use of uPA/PAI-1 for risk-adapted individualised therapy decisions in N0 breast cancer BACKGROUND Prior studies with the use of a prospect ive-retrospective design including archival tumor sample s have shown that gene-expression assays provide clinical ly useful prognostic information . However , a prospect ively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker . METHODS We performed a prospect i ve trial involving women with hormone-receptor-positive , human epidermal growth factor receptor type 2 (HER2)-negative , axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension ( or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade ) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features . A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue , and the results were used to calculate a score indicating the risk of breast-cancer recurrence ; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10 , indicating a very low risk of recurrence ( on a scale of 0 to 100 , with higher scores indicating a greater risk of recurrence ) . RESULTS Of the 10,253 eligible women enrolled , 1626 women ( 15.9 % ) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy . At 5 years , in this patient population , the rate of invasive disease-free survival was 93.8 % ( 95 % confidence interval [ CI ] , 92.4 to 94.9 ) , the rate of freedom from recurrence of breast cancer at a distant site was 99.3 % ( 95 % CI , 98.7 to 99.6 ) , the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7 % ( 95 % CI , 97.9 to 99.2 ) , and the rate of overall survival was 98.0 % ( 95 % CI , 97.1 to 98.6 ) . CONCLUSIONS Among patients with hormone-receptor-positive , HER2-negative , axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features , those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00310180 . ) The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction ( RT‐PCR ) assay underwent validation in 668 lymph node‐negative , estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program ( NSABP ) B‐14 . The predictive accuracy for treatment efficacy also underwent validation in 651 patients r and omized on NSABP B‐20 and 645 patients on NSABP B‐14 PURPOSE To provide evidence -based recommendations to practicing oncologists , surgeons , and radiation therapy clinicians to up date the 2005 clinical practice guideline on the use of sentinel node biopsy ( SNB ) for patients with early-stage breast cancer . METHODS The American Society of Clinical Oncology convened an Up date Committee of experts in medical oncology , pathology , radiation oncology , surgical oncology , guideline implementation , and advocacy . A systematic review of the literature was conducted from February 2004 to January 2013 in Medline . Guideline recommendations were based on the review of the evidence by Up date Committee . RESULTS This guideline up date reflects changes in practice since the 2005 guideline . Nine r and omized clinical trials ( RCTs ) met systematic review criteria for clinical questions 1 and 2 ; 13 cohort studies informed clinical question 3 . RECOMMENDATIONS Women without sentinel lymph node ( SLN ) metastases should not receive axillary lymph node dissection ( ALND ) .  Women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND ( in most cases ) . Women with SLN metastases who will undergo mastectomy should be offered ALND . These three recommendation are based on RCTs . Women with operable breast cancer and multicentric tumors , with ductal carcinoma in situ ( DCIS ) who will undergo mastectomy , who previously underwent breast and /or axillary surgery , or who received preoperative/neoadjuvant systemic therapy may be offered SNB . Women who have large or locally advanced invasive breast cancer ( tumor size T3/T4 ) , inflammatory breast cancer , or DCIS ( when breast-conserving surgery is planned ) or are pregnant should not undergo SNB . These recommendations are based on cohort studies and /or informal consensus . In some cases , up date d evidence was insufficient to up date previous recommendations BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma , but it does not fully account for the varied disease outcome . More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are c and i date s for systemic adjuvant therapy .  Our recent findings indicated that microvessel density ( count or grade ) in invasive breast carcinoma ( a measure of tumor angiogenesis ) is associated with metastasis and thus may be a prognostic indicator . PURPOSE This study was design ed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma . METHODS In a prospect i ve , blinded study of 165 consecutive patients , the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen . Using light microscopy , we counted microvessels per 200x field in the most active areas of neovascularization and grade d microvessel density . These findings were correlated , by univariate and multivariate analyses , with overall and relapse-free survival , axillary node status , and other prognostic indicators ( median follow-up , 51 months ) . RESULTS There was a highly significant ( P < or = .001 ) association of microvessel density with overall survival and relapse-free survival in all patients , including node-negative and node-positive subsets . All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis , compared with less than 5 % of the patients with breast carcinoma having 33 or fewer microvessels per 200x field . Moreover , microvessel density was the only statistically significant predictor of overall survival among node-negative women ( P < .001 ) . Only microvessel density ( P < .001 ) and histologic grade ( P = .04 ) showed statistically significant correlations with relapse-free survival in the node-negative subset . CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma ( I or II by International Union Against Cancer criteria ) . IMPLICATION S Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation . These patients could then be given systemic adjuvant therapy PURPOSE The primary purpose of this study was to measure the impact of the 21-gene Recurrence Score ® result on systemic treatment recommendations and to perform a prospect i ve health economic analysis in stage I-II , node-negative , oestrogen receptor positive ( ER+ ) breast cancer . METHODS Consenting patients with ER+ node negative invasive breast cancer and their treating medial oncologists were asked to complete question naires about treatment preferences , level of confidence in those preferences and a decisional conflict scale ( patients only ) after a discussion of their diagnosis and risk without knowledge of the Recurrence Score . At a subsequent visit , the assay result and final treatment recommendations were discussed prior to both parties completing a second set of question naires . A Markov health state transition model was constructed , simulating the costs and outcomes experienced by a hypothetical ' assay naïve ' population and an ' assay informed ' population . RESULTS One hundred and fifty-six patients across two cancer centres were enrolled . Of the 150 for whom successful assay results were obtained , physicians changed their chemotherapy recommendations in 45 cases ( 30 % ; 95 % confidence interval ( CI ) 22.8 - 38.0 % ) ; either to add ( 10 % ; 95 % CI 5.7 - 16.0 % ) or omit ( 20 % ; 95 % CI 13.9 - 27.3 % ) adjuvant chemotherapy . There was an overall significant improvement in physician confidence post-assay ( p<0.001 ) . Patient decisional conflict also significantly decreased following the assay ( p<0.001 ) . The simulation model found an incremental cost-effectiveness ratio of Canadian Dollars ( CAD ) $ 6630/ quality -adjusted life years ( QALY ) . CONCLUSION Within the context of a publicly funded health care system , the Recurrence Score assay significantly affects adjuvant treatment recommendations and is cost effective in ER+ node negative breast cancer Background We carried out a prospect i ve clinical study to evaluate the impact of the Recurrence  Score  ( RS ) on treatment decisions in early breast cancer ( EBC ) . Patients and methods A total of 379 eligible women with estrogen receptor positive ( ER+ ) , HER2-negative EBC and 0–3 positive lymph nodes were enrolled .  Treatment recommendations , patients ' decisional conflict , physicians ' confidence before and after knowledge of the RS and actual treatment data were recorded . Results Of the 366 assessable patients 244 were node negative ( N0 ) and 122 node positive ( N+ ) . Treatment recommendations changed in 33 % of all patients ( N0 30 % , N+ 39 % ) . In 38 % of all patients ( N0 39 % , N+ 37 % ) with an initial recommendation for chemoendocrine therapy , the post-RS recommendation changed to endocrine therapy , in 25 % ( N0 22 % , N+ 39 % ) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy , respectively . A patients ' decisional conflict score improved by 6 % ( P = 0.028 ) and physicians ' confidence increased in 45 % ( P < 0.001 ) of all cases . Overall , 33 % ( N0 29 % , N+ 38 % ) of fewer patients actually received chemotherapy  as compared with patients recommended chemotherapy pre-test . Using the test was cost-saving versus current clinical practice . Conclusion RS-guided chemotherapy decision-making result ed in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC Background : International guidelines , including NICE , recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+ , HER2-negative early breast cancer ( BC ) . We investigated the impact of adding this assay to st and ard pathological tests on clinicians’/ patients ’ treatment decisions and on patients ’ decisional conflict in the United Kingdom . Methods : In this prospect i ve multicentre study , eligibility criteria included : ER+ HER2-negative BC ( N0/Nmic for patients ⩽50 years ; ⩽3 positive lymph nodes for patients > 50 years ) and being fit for chemotherapy .  Physicians’/ patients ’ treatment choices and patients ’ decisional conflict were recorded pre- and post testing . Results : The analysis included 137 patients . Overall , adjuvant treatment recommendations changed in 40.7 % of patients , with the direction of the change consistent with the Recurrence Score results ( net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients ) . Patients ’ choices were generally consistent with physicians ’ recommendations . Post-testing , patients ’ decisional conflict decreased significantly ( P<0.0001 ) . In the 67 patients meeting the NICE criteria for testing , the recommendation change rate was 49.3 % . Conclusions : Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria , suggesting that this test could substantially alter treatment patterns in the United Kingdom Novel genetic profiling tests of breast cancer tissue have been shown to be prognostic for overall survival and predictive of local and distant rates of recurrence in breast cancer patients . One of these tests , Oncotype DXtrade mark , is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue , which allows physicians to predict subgroups of hormone-receptor-positive , node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy  to attain the best survival outcome . The results of the assay are converted to a recurrence score ( 0 - 100 ) that has been found to be predictive of 10- and 15-year local and distant recurrence in node-negative , estrogen-receptor-positive breast cancer patients . Previous studies have shown that patients with high recurrence scores benefit from adjuvant chemotherapy , whereas patients with low recurrence scores do not . To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score , the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer , a r and omized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ ( IDFS-DCIS ) survival in women with node-negative , estrogen-receptor-positive breast cancer with a recurrence score of 11 - 25 . The study was initiated in May 2006 and approximately 4500 patients will be r and omized . This article describes the rationale , methodology , statistical ana-lysis and implication s of the results on clinical practice Several independent r and omized controlled trials are initiated to investigate whether sentinel lymph node biopsy can be safely omitted in clinical ly node negative breast cancer patients with negative axillary ultrasound findings , who are treated with breast conserving therapy .  A consequence of omitting sentinel lymph node biopsy is absence of pathological lymph node status information . We aim ed to investigate the impact of omitting sentinel lymph node biopsy on adjuvant systemic treatment recommendations .  Data from all consecutive patients with invasive breast cancer and negative axillary ultrasound findings treated with breast conserving therapy and sentinel lymph node biopsy between 2008 and 2012 were collected from a prospect i ve data base . Two methods , Adjuvant ! Online and the Dutch breast cancer guideline 2012 , were used to determine the adjuvant systemic treatment recommendations of every patient . At first , each patient was considered to be lymph node negative , and secondly the patients ’ true pathological lymph node status was used . A total of 303 patients were consecutively included .  Pathological lymph node status was pN0 in 72.3 % , pN0(i+ ) in 12.9 % , pN1mi+ in 5.6 % , pN1 in 7.3 % , and pN2 in 2.0 % of the patients . The decision to recommend  adjuvant systemic treatment  changed due to the pathological lymph node status in 1.0 % of the patients ( 3/303 ) when using Adjuvant ! Online and in 3.6 % ( 11/303 ) when using the 2012 Dutch breast cancer guideline . The impact of the pathological lymph node status on adjuvant systemic treatment recommendations in clinical ly node negative breast cancer patients with negative axillary ultrasound findings treated with breast conserving therapy is limited . The safety of omitting the sentinel lymph node biopsy should be confirmed by the initiated r and omized controlled trials PURPOSE Adjuvant ! is a st and ardized vali date d decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy . Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features . PATIENTS AND METHODS A sample of 465 patients with hormone receptor ( HR ) -positive breast cancer with zero to three positive axillary nodes who did ( n = 99 ) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay .  Histologic grade and HR expression were evaluated locally and in a central laboratory . RESULTS Recurrence Score ( RS ) was a highly significant predictor of recurrence , including node-negative and node-positive disease ( P < .001 for both ) and when adjusted for other clinical variables . RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant ! that was adjusted to 5-year outcomes . The 5-year recurrence rate was only 5 % or less for the estimated 46 % of patients who have a low RS ( < 18 ) . CONCLUSION The 21-gene assay was a more accurate predictor of relapse than st and ard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy  and provides information that is complementary to features typically used in anatomic staging , such as tumor size and lymph node involvement . The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments To determine if older women with early stage breast cancer have sufficient decisional support during their breast cancer journey , a question naire-based study was conducted at the Sunnybrook Odette Cancer Centre , in Toronto , Ontario , Canada . Women with stages I and II breast cancer , ≥60 years , were contacted upon completion of their adjuvant treatment . A question naire was developed based on focus groups , the literature , and consultation with patients and a multidisciplinary team of experts . The question naire was divided into six domains as follows : ( 1 ) information support surrounding diagnosis , ( 2 ) impact of cancer diagnosis on the patient , ( 3 ) quality of interaction with healthcare team , ( 4 ) decisional support from the healthcare team , ( 5 ) additional information needs surrounding treatment decision , and ( 6 ) information support during radiation treatment .  Ninety-two of 137 patients approached were included in the analysis . Ninety percent were > 60 years at the time of diagnosis and 65 % had stage I invasive breast cancer . The majority of women received adequate decisional support during their cancer journey . Approximately 90 % of women indicated that they received a high level of support during their cancer diagnosis . We found no significant differences in overall decisional support based on age at diagnosis , education level , ethnicity , or the presence of co-morbidities . However , participants desired additional educational re sources such as a worksheet , consultation summary , or workbook to assist in making a treatment decision . The majority of participants felt that they had sufficient support while making a treatment decision for breast cancer Introduction : Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing . The Oncotype DX ® 21-gene assay is predictive of distant recurrence in ER-positive , HER2-negative early breast cancer . We aim ed to evaluate the impact of the  Recurrence Score ® ( RS ) on treatment decisions and physician perceptions in Turkey . We also studied correlations between RS and routine risk factors . Patients and Methods : Ten academic centers across Turkey participated in this prospect i ve trial . Consecutive breast cancer patients with pT1 - 3 , pN0-N1mic , ER-positive , and HER2-negative tumors were identified at multidisciplinary tumor conferences . The initial treatment decision was recorded before tumor blocks were sent to the central laboratory . Each case was brought back to tumor conference after receiving the RS result . Both pre- and post-RS treatment decisions and physician perceptions were recorded on question naire forms . Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses . Results : Ten centers enrolled a total of 165 patients .  The median tumor size was 2 cm . Of 165 patients , 57 % had low RS , 35 % had intermediate RS , and 8 % had high RS , respectively . The overall rate of change in treatment decision was 33 % . Initially , chemotherapy followed by hormonal therapy ( CT+HT ) was recommended to 92 ( 56 % ) of all patients , which decreased to 61 ( 37 % ) patients post-RS assay ( p<0.001 ) . Multivariate analysis indicated that progesterone receptor ( PR ) and Ki-67 scores were significantly related to RS . Conclusion : Oncotype DX testing may provide meaningful additional information in carefully selected patients TPS104 Background : Multi-gene tumor assays have provided clinical ly useful prognostic information for patients with HR receptor and node-positive breast cancer . The 21-gene RS was shown to be prognostic for patients treated with tamoxifen alone , and exploratory studies suggested that it may be predictive of benefit from chemotherapy . In retrospective analyses from S8814 , patients with low RS appeared to get no benefit from adjuvant CAF chemotherapy , while those with higher RS did . These retrospective data require validation , especially since more modern chemotherapy might be more effective than the regimen used in S8814 . In January 2011 SWOG activated a trial to test the efficacy of using modern chemotherapy regimens in node positive patients with low RS , whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value . The trial is similar to the Tailor RX study , but focuses on a node-positive population with low and intermediate RS . METHODS Phase III r and omized clinical trial of best endocrine therapy vs. best endocrine therapy and chemotherapy .  Patients with 1 to 3 positive lymph nodes , HR-positive and HER2-negative invasive breast cancer with RS ≤ 25 are eligible for r and omization . Approximately , 9,400 patients will be screened to r and omize 4000 , stratified by RS ( 0 - 13 vs. 14 - 25 ) , menopausal status , and axillary surgery ( sentinel node vs.full dissection ) . Patients will be informed of their RS . Trial is powered on finding a significant interaction of treatment assignment and the continuous RS value and subsequently deriving a cutpoint for using the assay to guide treatment decisions . Patients who consent to screening are required to consent to banking of the tumor tissue and blood for further studies . Patient Reported Outcomes will be collected pre , post screening and post-r and omization . The study also has a cost-effectiveness analysis . Status : Open nationwide through participating NCI-funded cooperative groups . NCT01272037 PURPOSE The goal of the computer program Adjuvant ! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy . METHODS Actuarial analysis was used to project outcomes of patients with and without  adjuvant therapy  based on estimates of prognosis largely derived from Surveillance , Epidemiology , and End- Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of r and omized trials of adjuvant therapy . These estimates can be refined using the Prognostic Factor Impact Calculator , which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results . RESULTS From the entries of patient information ( age , menopausal status , comorbidity estimate ) and tumor staging and characteristics ( tumor size , number of positive axillary nodes , estrogen receptor status ) , baseline prognostic estimates are made . Estimates for the efficacy of endocrine therapy ( 5 years of tamoxifen ) and of polychemotherapy ( cyclophosphamide/methotrexate/fluorouracil-like regimens , or anthracycline-based therapy , or therapy based on both an anthracycline and a taxane ) can then be used to project outcomes presented in both numerical and graphical formats . Outcomes for overall survival and disease-free survival and the improvement seen in clinical trials , are reasonably modeled by Adjuvant ! , although an ideal validation for all patient subsets with all treatment options is not possible . Additional speculative estimates of years of remaining life expectancy and long-term survival curves can also be produced . Help files supply general information about breast cancer . The program 's Internet links supply national treatment guidelines , cooperative group trial options , and other related information . CONCLUSION The computer program Adjuvant ! can play practical and educational roles in clinical setting 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
RECOMMENDATIONS In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2 , the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX , EndoPredict , PAM50 , Breast Cancer Index , and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer .
No biomarker except for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens .
PURPOSE To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer .