Comparison of outcome prediction in node-negative breast cancer based on biomarkers uPA/PAI-1 or Adjuvant Online using the 10-year follow-up of the randomized multicenter Chemo N0 trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 534-534 ◽  
Author(s):  
U. Euler ◽  
C. Meisner ◽  
C. Friedel ◽  
M. Schmidt ◽  
M. Untch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Clinical Trial ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Computer Program ◽  
Risk Patients ◽  
The Individual ◽  
Pai 1

534 Background: Chemo N0 was the first multicenter randomized clinical trial in breast cancer using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection. Chemo N0 validated uPA/PAI-1 as clinically relevant parameters for risk assessment in N0 breast cancer. About 50% of N0 patients have low uPA/PAI-1 in their primary tumor with excellent 5-year OS (>95%), even without adjuvant therapy. Patients with high uPA/PAI-1 benefit from adjuvant chemotherapy. We evaluated whether biomarkers can predict outcome more accurately than a computer-program. Methods: In Chemo N0, patients (n=689, 1993–98) were stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed 10-year OS in Chemo N0. Results: 81/151 patients with already available complete follow-up data 10 years after trial start have 10-year OS results. Median 10-year OS estimated by Adjuvant Online was 77.1% (median 78.6%) taking into account administered adjuvant therapy. 10-year Chemo N0 follow-up revealed an observed 10-year OS of 66.7% (27/81 deceased). 64/81 did not receive chemotherapy: In high-risk untreated patients (n=22), 10-year OS was 54.6% vs. estimated 75.0%. In CMF-treated patients (all high-risk, n=17), observed OS was 58.8% vs. estimated 74.6%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant Online in data from a randomized clinical trial. In patients with high uPA/PAI-1, the individual 10-year OS calculated by Adjuvant Online seems to be underestimated compared to observed patient outcome. Further follow-up data will show whether uPA/PAI-1 can predict the individual course of disease more precisely than a computer-program based on large clinical data sets. Final Chemo N0 10-year follow-up is currently being completed. No significant financial relationships to disclose.

Molecular risk estimation and adjuvant chemotherapy in node-negative breast cancer patients—A status report of the prospective clinical trial NNBC 3-Europe

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10503-10503 ◽  
Author(s):  
D. M. Paepke ◽  
F. Herbst ◽  
K. Annecke ◽  
N. Gaskill ◽  
F. Sweep ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Molecular Markers ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Low Risk ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Risk Patients ◽  
Pai 1

10503 Background: Feasibility of risk assessment in node negative breast cancer using the invasion markers urokinase-type plasminogen activator uPA and its inhibitor PAI-1 has been demonstrated in several prospective and retrospective studies and in a large meta analysis. Patients with low uPA and/or PAI-1 concentrations in tumor tissue levels have an excellent 5-year overall survival (>95%) even without any adjuvant therapy. Use of these molecular markers may spare adjuvant chemotherapy in approximately one half of node-negative breast cancer patients. Particulary, patients with an intermediate grade tumor can easily be differentiated in low and high risk. In addition, patients with high uPA and/or PAI-1 level seem to benefit from adjuvant chemotherapy. The NNBC-3-Europe trial seeks to answer two questions: 1. Is risk assessment by molecular markers uPA/PAI-1 superior to that by clinico-pathological factors regarding identification of low-risk patients? 2. Is adjuvant chemotherapy with anthracycline-taxane sequence (FEC-Docetaxel) superior to standard FEC in high-risk patients? Methods: In the NNBC-3-Europe trial, participating centres opt to either perform risk estimation by clinico-pathological factors or by the uPA and PAI-1 concentration in tumor tissue biopsies. Low-risk patients will be observed without adjuvant chemotherapy. High-risk patients are randomised based on the kind of adjuvant chemotherapy. Patients with steroid hormone receptor positive tumors receive adequate endocrine therapy. Results: Of the first 506 patients in the study arm with molecular risk assessment, 62 had a grade 1 tumors, and 184 had grade 3 tumors. Among grade 2 tumors (n = 260), 87 had low uPA/PAI-1. 173 patients presented with high levels. About 30% of the patients were allocated to the low-risk group using uPA/PAI-1. Conclusions: An adjuvant chemotherapy trial based on uPA/PAI-1 determination in the primary tumor is feasible in a multicentre setting. Applying these molecular markers for risk assessment, at this stage of the study, adjuvant chemotherapy could be spared in almost one third of N0 patients. It is performed in association with the EORTC PathoBiology Group Receptor und the German AGO Breast Group. [Table: see text]

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

1995 ◽  
Vol 13 (3) ◽  
pp. 547-552 ◽  
Author(s):  
T J Powles ◽  
T F Hickish ◽  
A Makris ◽  
S E Ashley ◽  
M E O'Brien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Response Rate ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Chemoendocrine Therapy ◽  
Primary Operable Breast Cancer

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Prospective surveillance using l-dex monitoring results in significant reductions in the chronic rate of breast cancer related-lymphedema (BCRL) in high-risk breast cancer patients.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 118-118
Author(s):  
Alison L. Laidley ◽  
Beth V. Anglin
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Clinical Stage ◽  
Breast Cancer Patients ◽  
Prospective Surveillance ◽  
Complete Decongestive Therapy ◽  
Risk Patients ◽  
Breast Cancer Related Lymphedema ◽  
Stage 1

118 Background: Survivorship represents an increasing focus in the management of breast cancer with chronic toxicities including breast cancer-related lymphedema (BCRL). This study looked at prospective surveillance using bioimpedance spectroscopy (BIS) to reduce risks of chronic BCRL requiring referral for complete decongestive therapy (CDT). Methods: 132 patients at high-risk for the development of BCRL were prospectively followed using BIS with serial monitoring. This included a pre-operative baseline assessment and a minimum of two post-operative follow up assessments. Interventions were initiated when the L-Dex score increased by greater than 10 units from baseline and consisted of conservative treatment with a compression sleeve for four weeks. Patients were also clinically monitored for the development of BCRL. Results: Median follow-up was 19.3 months (range 4-54 mos). Of the 132 patients evaluated, 24 (18.1%) were subsequently diagnosed with elevated L-Dex scores and underwent intervention. Of the 24 that underwent treatment, 14 (58%) had resolution of their elevated L-Dex scores following four weeks of therapy with 10 having persistent elevations and clinical BCRL which necessitated referral to physical therapy for CDT. A further 7 subjects were diagnosed and not treated for elevated L-Dex scores, but had complete resolution (return to baseline) at last visit. At last follow-up, only 10 patients (7.6 %) had unresolved, clinical stage 1, BCRL. Conclusions: The use of L-Dex to prospectively follow our high-risk patients and prescribe intervention with a compression sleeve for 4 weeks when scores are elevated resulted in only a 7.6 % rate of stage 1, chronic BCRL. This rate of BCRL has been reported as 15-20%, suggesting that a prospective program of screening and intervention using L-Dex does result in clinically meaningful reductions in this long-term sequelae of treatment.

Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism

2015 ◽  
Vol 81 (7) ◽  
pp. 663-668 ◽  
Author(s):  
Casey J. Allen ◽  
Clark R. Murray ◽  
Jonathan P. Meizoso ◽  
Juliet J. Ray ◽  
Laura F. Teisch ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Trauma Patients ◽  
Clotting Time ◽  
Coagulation Profile ◽  
Profile Score ◽  
Risk Patients ◽  
Profile Changes

We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 ( P = 0.504). TPX was initiated 3.4 ± 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25–37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 ( P < 0.001); correcting from 7.75 (6.45–8.90) minutes to 10.45 (7.90–15.25) minutes ( P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 ( P < 0.001); increasing from 61(55–65) mm to 75(69–80) mm ( P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R2 = 0.095, P = 0.008) and at Day 7 (r = 0.516, R2 = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R2 = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients.

Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel As Adjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study

2013 ◽  
Vol 31 (20) ◽  
pp. 2593-2599 ◽  
Author(s):  
Miguel Martín ◽  
Amparo Ruiz ◽  
Manuel Ruiz Borrego ◽  
Agustí Barnadas ◽  
Sonia González ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Weekly Paclitaxel ◽  
Node Negative ◽  
Primary Surgery ◽  
Disease Free

Purpose Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. Patients and Methods Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. Results After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). Conclusion For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.

Recurrence risk stratification by Dutch clinical risk criteria for early-stage luminal breast cancer patients in Taiwan: A population-based analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12509-e12509
Author(s):  
Lei Lei ◽  
Han-Ching Chan ◽  
Wang Xiao Jia ◽  
Tzu-Pin Lu ◽  
Skye Hung-Chun Cheng
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Risk Groups ◽  
Low Risk ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Risk Patients

e12509 Background: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.

scholarly journals Clinical trial results of the HER-2/neu(E75) vaccine to prevent breast cancer recurrence in high-risk patients

Cancer ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2594-2602 ◽  
Author(s):  
Elizabeth A. Mittendorf ◽  
Guy T. Clifton ◽  
Jarrod P. Holmes ◽  
Kevin S. Clive ◽  
Ritesh Patil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
High Risk Patients ◽  
Risk Patients ◽  
Her 2 ◽  
Clinical Trial Results

Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for improved management in node-negative (N0) breast cancer: Experiences from the ongoing multicenter trial NNBC 3-Europe

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11081-11081 ◽  
Author(s):  
M. M. Persing ◽  
D. Paepke ◽  
M. Schmidt ◽  
C. Veyret ◽  
D. Augustin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Tumor Tissue ◽  
Tumor Grade ◽  
Low Risk ◽  
Fresh Frozen ◽  
Breast Group ◽  
Pai 1

11081 Risk-assessment in N0 breast cancer is still controversial. In line with St. Gallen, only few patients (pts) are considered at such low risk of relapse, that adjuvant chemotherapy could be avoided. Various groups have started clinical trials aimed at improved risk-assessment by gene or protein analysis of the primary tumor. We launched the NNBC 3-Europe trial asking the following questions: Is the identification of low- risk pts by the invasion markers uPA and PAI-1 more effective than by St. Gallen criteria? Is adjuvant chemotherapy using an anthracycline- taxane sequence superior to standard FEC in N0 high-risk pts? The centres of the NNBC 3 trial had to choose their mode of risk- assessment (either St. Gallen criteria or uPA/PAI-1) prior to recruitment. High-risk pts receive chemotherapy randomly assigned to FEC-100*3 followed by Docetaxel-100*3 (FEC-Doc), or FEC-100*6. No adjuvant chemotherapy is given to low-risk pts. Pts with hormone receptor positive tumors receive standard endocrine therapy. To date, 1206 pts in 57 centres have been registered. Using fresh frozen tumor tissue, uPA and PAI-1 are tested in nine laboratories; inter-laboratory quality assurance is performed. In 141 of 1188 evaluable pts, St Gallen criteria were used. In the biological risk-assessment group, 150 of 1047 tumors (14.3%) were well differentiated, thus regarded as low-risk. Using both, tumor grade and uPA/PAI-1, 35.3% of the pts were considered low-risk, whereas the remaining 64.7% high-risk pts received adjuvant chemotherapy (FEC-Doc, n=334, or FEC, n=343). Multicenter prospective risk assessment based on testing of fresh frozen (or paraffin- embedded) tumor tissue is sophisticated. All trials with similar approach (MINDACT, TAILORx) had a long preparation phase including thorough assay validation. The ongoing NNBC-3 trial demonstrates that inclusion of pts based on testing of fresh frozen material is feasible in a routine setting. Risk-group distribution is as expected. The study is planned to recruit 5,700 pts and it is performed in cooperation with the EORTC Patho-Biology Group, the German AGO Breast Group, and the German Breast Group (GBG). Unrestricted grants by Sanofi-Aventis and Pfizer. [Table: see text]

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