scholarly journals Neural Network Analysis of Follow-Up Data in Primary Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 116-122 ◽  
Author(s):  
N. Harbeck ◽  
R. Kates ◽  
K Ulm ◽  
H. Graeff ◽  
M. Schmitt
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Risk Group ◽  
Neural Network Analysis ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Neural Network ◽  
Pai 1

This paper reports on the performance of a recently developed neural network environment incorporating likelihood-based optimization and complexity reduction techniques in the analysis of breast cancer follow-up data with the goal of building up a clinical decision support system. The inputs to the neural network include classical factors such as grading, age, tumor size, estrogen and progesterone receptor measurements, as well as tumor biological markers such as PAI-1 and uPA. The network learns the structural relationship between these factors and the follow-up data. Examples of neural models for relapse-free survival are presented, which are based on data from 784 breast cancer patients who received their primary therapy at the Department of Obstetrics and Gynecology, Technische Universität München, Germany. The performance of the neural analysis as quantified by various indicators (likelihood, Kaplan-Meier curves, log-rank tests) was very high. For example, dividing the patients into two equally sized groups based on the neural score (i.e., cutoff = median score) leads to an estimated difference in relapse-free survival of 40% or better (80% vs. 40%) after 10 years in Kaplan-Meier analysis. Evidence for factor interactions as well as for time-varying impacts is presented. The neural network weights included in the models are significant at the 5% level. The use of neural network analysis and scoring in combination with strong tumor biological factors such as uPA and PAI-1 appears to result in a very effective risk group discrimination. Considerable additional comparison of data from different patient series will be required to establish the generalization capability more firmly. Nonetheless, the improvement of risk group discrimination represents an important step toward the use of neural networks for decision support in a clinical framework and in making the most of biological markers.

scholarly journals The Alterations and Potential Roles of MCMs in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xinyu Liu ◽  
Ying Liu ◽  
Qiangshan Wang ◽  
Siqi Song ◽  
Lingjun Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Network ◽  
Relapse Free Survival ◽  
Minichromosome Maintenance ◽  
Free Survival ◽  
Oncomine Database ◽  
Kaplan Meier ◽  
Eukaryotic Dna ◽  
Coexpressed Genes ◽  
Kaplan Meier Plotter

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

The association of clinical-pathologic factors and Oncotype Dx recurrence score (RS) in the outcome of early stage breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 55-55
Author(s):  
Manjeet Chadha ◽  
Robert Stewart ◽  
Jonathan Wallach
Keyword(s):  
Breast Cancer ◽  
Patient Outcomes ◽  
Early Stage ◽  
Brca Mutation ◽  
Recurrence Score ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Pathologic Features ◽  
Oncotype Dx Recurrence Score

55 Background: Oncotype Dx recurrence score (RS) is routinely used to guide systemic therapy based on the estimated risk for distant relapse. Patients with early stage disease are also at risk for locoregional recurrence, and in some instances local relapse is the only site of failure. The objective of this study is to evaluate patient outcomes in association with known clinical-pathologic risk factors and RS. Observations in context of known clinical-pathologic features and RS may have important clinical implications relative to adjuvant locoregional therapy. Methods: This is an IRB approved retrospective study that includes patients with unilateral breast cancer and in whom the RS was reported. A total of 716 patients met this defined criteria. Seventy two percent underwent breast conserving therapy (BCS) and 28% underwent mastectomy; 68% had stage I and the remaining had > Stage II disease.The clinical-pathologic variables including age, stage, BRCA mutation, extent of surgery, and RS were studied in evaluating patient outcomes. Results: The median age was 56 years (27 to 84 years). The overall distribution of RS reported as low (18), intermediate (19-30), and high ( > 31) was 59%, 31%, and 10%, respectively. This distribution ratio was no different among patients treated with BCS and mastectomy. However, among BRCA mutation carriers there was a higher incidence of the high RS.Overall, the median follow up was over 3 years, and 25% of the patients have been followed over 5 years. The 3-year and 5-year any relapse-free survival was 93% and 89%, respectively. Age was significantly associated with observed inferior any relapse-free survival; 85% and 91% in women < 40 years vs > 40 years, respectively (p = 0.018). On univariate analysis, RS had no significant association with local regional relapse free survival. Further, associations between the clinical-pathologic features and RS using multivariate analysis will be presented. Conclusions: Observations with early follow up do not suggest a select role of RS in guiding risk tailored local regional therapy. Longer follow will further our understanding of patients at risk for local regional relapse.

scholarly journals Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5185-5187 ◽  
Author(s):  
Max S. Topp ◽  
Nicola Gökbuget ◽  
Gerhard Zugmaier ◽  
Evelyn Degenhard ◽  
Marie-Elisabeth Goebeler ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Study Cohort ◽  
Clinical Relapse ◽  
Phase 2 ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Kaplan Meier ◽  
B Lineage

Abstract Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell–engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome–negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The original study and this follow-up study are registered at www.clinicaltrials.gov as NCT00198991 and NCT00198978, respectively.

scholarly journals Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6059
Author(s):  
William Jacot ◽  
Aurélie Maran-Gonzalez ◽  
Océane Massol ◽  
Charlotte Sorbs ◽  
Caroline Mollevi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Histological Grade ◽  
Univariate Analysis ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Few Data

HER2-low breast cancer (i.e., HER 1+ or 2+, without gene amplification) is an emerging subtype for which very few data are available, especially within the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression and its prognostic value in a large retrospective series of patients with non-metastatic TNBC (median age: 57.7 years; range: 28.5–98.6). Among the 296 TNBC samples, 83.8% were HER2 0, 13.5% were HER2 1+, and 2.7% were HER2 2+ (HercepTestTM and 2018 ASCO/CAP guidelines for HER2 scoring). CK5/6 and/or EGFR-expressing androgen receptors and FOXA1-expressing tumors were classified as basal-like (63.8%) and molecular apocrine-like (MA, 40.2%), respectively. Compared with HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower histological grade (1/2) (35.4% vs. 18.2%, p = 0.007) and MA profile (57.5% vs. 36.7%, p = 0.008). Moreover, patients with HER2 1+/2+ tumors were older (p = 0.047). After a median follow-up of 9.7 years, HER2 2+ tumors (compared with HER2 0/1+ tumors) were associated with worse relapse-free survival (RFS) (HR = 3.16, 95% CI [1.27; 7.85], p = 0.034) in a univariate analysis. Overall survival (OS) and RFS were not different in the HER2 0 and 1+/2+ groups. HER2 levels were not significantly associated with OS or RFS in a multivariate analysis.

Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 292-292
Author(s):  
C. M. Kelly ◽  
M. C. Green ◽  
K. Broglio ◽  
L. Pusztai ◽  
E. Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Subgroup Analysis ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Phase Iii Trial ◽  
Free Survival

292 Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens. Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant). Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39). Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.

Serum CA 15.3, CEA and ESR Patterns in Breast Cancer

1997 ◽  
Vol 12 (4) ◽  
pp. 168-173 ◽  
Author(s):  
M. Rubach ◽  
J.J. Szymendera ◽  
J. Kamińska ◽  
M. Kowalska
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Peak Level ◽  
Serum Markers ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Ca 15.3

Serum CA 15.3, CEA and ESR were longitudinally determined in 298 patients with breast cancer during postsurgical follow-up and/or therapy. Observation lasted until the death of the patient or at least for three years. With regard to longitudinal serum markers and ESR curves, four different patterns have been identified: pattern I: the markers and ESR stayed at normal levels; pattern II: the markers and ESR decreased from a peak level; pattern III: the markers and ESR fluctuated widely; pattern IV: the markers and ESR increased steadily. We have looked at overall survival (OS) and relapse-free survival (RFS) versus longitudinal CA 15.3, CEA and ESR patterns. Univariate Cox regression analysis showed that OS and RFS were significantly associated with all four patterns.

scholarly journals Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance)

2014 ◽  
Vol 32 (22) ◽  
pp. 2311-2317 ◽  
Author(s):  
Lawrence N. Shulman ◽  
Donald A. Berry ◽  
Constance T. Cirrincione ◽  
Heather P. Becker ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Duration Of Therapy ◽  
The One ◽  
Absolute Advantage

Purpose Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. Patients and Methods Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. Results With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. Conclusion This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.

Meta-analysis of 59 gene expression based biomarker candidates predicting survival after tamoxifen treatment in breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11564-e11564
Author(s):  
Balazs Gyorffy ◽  
Mate Kormos ◽  
Andras Lanczky ◽  
Zsuzsanna Mihaly
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Tamoxifen Treatment ◽  
Endocrine Treatment ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Microarray Datasets

e11564 Background: To date, three molecular markers (ER, PR and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment by evaluating these in a meta-analysis of available microarray datasets with known treatment and follow-up. Methods: Biomarker candidates were identified in Pubmed 2007-2012 and in the 2010-2012 ASCO and SABCS abstracts. Breast cancer microarray datasets were downloaded from GEO and EGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. In the transcriptomic datasets, only patients with tamoxifen treatment for relapse-free survival and endocrine treatment for overall survival were eligible. The raw microarray data was re-processed and integrated into two databases. Relapse free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival (OS). Statistical significance was set at p<0.01. Results: The transcriptomic datasets included 667 GEO-based and 1208 EGA-based patient samples. All together 59 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC=0.64, p=2.3E-07), MAPT (AUC=0.62, p=7.8E-05), SLC7A5 (AUC=0.62, p=9.2E-05) and TP53 (AUC=0.60, p=1.2E-03). Further genes significantly correlated to relapse-free survival include BTG2, HOXB7, DRG1, CXCL10, BCL2, TPM4, IGF1R and SMC3. Correlation to overall survival was significant for PGR (HR=0.67, p=1.7E-04), MAPT (HR=0.7, p=7.2E-04) and SLC7A5 (HR=1.6, p=1.6E-05). None of the remaining genes including ESR1 reached statistical significance for relapse-free survival. Conclusions: We validated two genes (MAPT and SLC7A5) as being capable to select those patients most likely benefit from tamoxifen treatment.

scholarly journals Efficacy of Early Diagnosis and Treatment in Women with a Family History of Breast Cancer

1999 ◽  
Vol 15 (1-3) ◽  
pp. 179-186 ◽  
Author(s):  
Pål Møller ◽  
Marta M. Reis ◽  
Gareth Evans ◽  
Hans Vasen ◽  
Neva Haites ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Risk ◽  
Age At Diagnosis ◽  
Pathological Stage ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
History Of ◽  
Distant Spread

BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality.METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan—Meier survival plots.RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first (“prevalence”) round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+.CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of “breast awareness” as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.

scholarly journals Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

Rheumatology ◽  
2020 ◽  
Author(s):  
Giorgia Martini ◽  
Laura Saggioro ◽  
Roberta Culpo ◽  
Fabio Vittadello ◽  
Alessandra Meneghel ◽  
...  
Keyword(s):  
Assessment Tool ◽  
Inactive Disease ◽  
Rank Test ◽  
Localized Scleroderma ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Juvenile Localized Scleroderma

Abstract Objectives To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma. Methods Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan–Meier analysis. Results MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy. Conclusion The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.

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