The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Widschwendter P
PROVIDER: S-EPMC4575482 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Publications
The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial.
Widschwendter Peter P Friedl Thomas Wp TW Schwentner Lukas L DeGregorio Nikolaus N Jaeger Bernadette B Schramm Amelie A Bekes Inga I Deniz Miriam M Lato Krisztian K Weissenbacher Tobias T Kost Bernd B Andergassen Ulrich U Jueckstock Julia J Neugebauer Julia J Trapp Elisabeth E Fasching Peter A PA Beckmann Matthias W MW Schneeweiss Andreas A Schrader Ines I Rack Brigitte B Janni Wolfgang W Scholz Christoph C
Breast cancer research : BCR 20150918
<h4>Introduction</h4>Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.<h4>Methods</h4>This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25. ...[more]
Similar Datasets
Project description:BackgroundWhen chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients.MethodsA total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ??35?years, tumor larger than 2?cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC???Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC???Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety.ResultsNo differences were observed in the 5-year DFS or OS between FEC???Doc and FEC???Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P?=?0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P?=?0.60) for OS. For patients treated with FEC???Doc and FEC???Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively.ConclusionAdding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting.Trial registrationClinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.
| S-EPMC7583247 | biostudies-literature
Project description:PurposeFew data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer.MethodsThe Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients.ResultsThe data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor-negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF.ConclusionAddition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.
| S-EPMC8966968 | biostudies-literature
Project description:BackgroundInvasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival.MethodsFrom 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan-Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models.ResultsIn the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77-1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85-1.50, p = 0.414) for OS, 1.21 (95% CI 0.89-1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73-1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients.ConclusionsOur results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.
| S-EPMC10722735 | biostudies-literature
Project description:Changes in gene expression were consistent with mechanism of action and show that clinical response to treatment with belimumab is associated with significant decrease in profibrotic genes and pathways. Additional study is needed to determine the role of belimumab in the treatment of dcSSc
2018-03-01 | GSE97248 | GEO
Project description:ObjectiveThe objective of this study is to compare the implant stability of Hiossen ET III implants with its new hydrophilic (NH) surface and Hiossen ET III implants with the sandblasted and acid-etched (SA) surface.Materials and methodsPatients required at least two teeth to be rehabilitated with a fixed, implant-supported restoration, consecutively enrolled. Patients randomly received SA surface implants (SA group) or SA implants with a newly developed bioabsorbable apatite nanocoating (NH group). Outcome measures were implant and prosthetic survival rate, complications, insertion torque, and implant stability quotient (ISQ) measured at implant placement and every week up to 8 weeks after implant placement. Comparison between groups was made by unpaired t-test, while the comparison between each follow-up will be made by paired t-tests to detect any change during the follow-up. Complications and failures were compared using Fisher's exact test.ResultsA total of 14 patients were treated with 28 implants (14 SA and 14 NH). No implant and prosthesis failed 4 months after implant placement. No complications were experienced. At the 2nd week after implants placement, two implants in the SA group showed discontinuous measurements versus none in the NH group (p = 0.4815). Implants unscrewed during ISQ measurements and were rescrewed. Data recording stopped for 6 weeks. Both implants osseointegrated without any further complication. The NH implants did not show physiological ISQ decrease between 2nd and 4th week after implant placement, showing a more even pattern of ISQ values compared with SA implants (77.1 ± 4.6 vs. 72.9 ± 11.5; difference: 4.2 ± 12.1; p = 0.258). High ISQ values were found in both groups at each time point.ConclusionsNH implants are a viable alternative to SA surface, as they seem to avoid the ISQ drop during the remodeling phase.
| S-EPMC6635964 | biostudies-literature
Project description:Durvalumab with olaparib was one of the experimental regimens evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2- and HR+HER2- signatures. We hypothesized that (pre-treatment) expression-based immune signatures may predict response to the immune checkpoint inhibitor durvalumab and signatures related to DNA repair deficiency (DRD) may associate with response to olaparib. In this analysis, we assessed 13 expression based signatures related to immune, DRD, proliferation and estrogen signaling as specific predictor of pathologic complete response (pCR) to durvalumab/olaparib.
2021-06-10 | GSE173839 | GEO
Project description:PurposePrevious studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented.MethodsWomen ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens.ResultsA total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred.ConclusionAt 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.
| S-EPMC7526720 | biostudies-literature
Project description:Experimental therapeutic oncology agents are often combined to circumvent tumor resistance to individual agents. However, most combination trials fail to demonstrate sufficient safety and efficacy to advance to a later phase. This study collected survey data on phase 1 combination therapy trials identified from ClinicalTrials.gov between January 1, 2003 and November 30, 2017 to assess trial design and the progress of combinations toward regulatory approval. Online surveys (N = 289, 23 questions total) were emailed to Principal Investigators (PIs) of early-phase National Cancer Institute and/or industry trials; 263 emails (91%) were received and 113 surveys completed (43%). Among phase 1 combination trials, 24.9% (95%CI: 15.3%, 34.4%) progressed to phase 2 or further; 18.7% (95%CI: 5.90%, 31.4%) progressed to phase 3 or regulatory approval; and 12.4% (95%CI: 0.00%, 25.5%) achieved regulatory approval. Observations of "clinical promise" in phase 1 combination studies were associated with higher rates of advancement past each milestone toward regulatory approval (cumulative OR = 11.9; p = 0.0002). Phase 1 combination study designs were concordant with Clinical Trial Design Task Force (CTD-TF) Recommendations 79.6% of the time (95%CI: 72.2%, 87.1%). Most discordances occurred where no plausible pharmacokinetic or pharmacodynamic interactions were expected. Investigator-defined "clinical promise" of a combination is associated with progress toward regulatory approval. Although concordance between study designs of phase 1 combination trials and CTD-TF Recommendations was relatively high, it may be beneficial to raise awareness about the best study design to use when no plausible pharmacokinetic or pharmacodynamic interactions are expected.
| S-EPMC6558040 | biostudies-literature
Project description:Importance:Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective:To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants:In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions:The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures:A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results:Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P?=?.052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P?=?.38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P?=?.98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P?=?.80). Conclusions and Relevance:These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration:ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.
| S-EPMC7348682 | biostudies-literature
Project description:Rationale: Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutritional regimes. We therefore hypothesize that a ketogenic diet improves sepsis treatment. Objectives: We investigated the safety and feasibility of a ketogenic diet in sepsis patients. Methods: We conducted a monocentric open-labeled randomized controlled trial (DRKS00017710) enrolling adult sepsis patients randomly assigned to either ketogenic or standard high-carbohydrate diet for 14 days with follow-up until day 30. The primary outcome measure was β-hydroxybutyrate serum concentration on day 14. Secondary outcomes included safety, clinical and immunological changes. Measurements and Main Results: 40 critically ill septic patients were assigned to the study groups. Increase in β-hydroxybutyrate concentrations from baseline to day 14 was markedly greater under ketogenic diet (1.2 ±0.9) compared to controls (-0.3 ±0.4); estimated mean difference 1.4 (95%-CI 1.0-1.8; p<0.0001). During ketogenic diet, no patient required insulin treatment beyond day 4, whereas 35% to 60% of control patients did (p=0.0095). Metabolic side effects were not observed under ketogenic diet. Ventilation-free (IRR 1.7; 95%-CI: 1.5 to 2.1; p<0.0001), vasopressor-free (IRR 1.7; 95%-CI: 1.5 to 2.0; p<0.0001), dialysis-free (IRR 1.5; 95%-CI: 1.3 to 1.8; p<0.0001), and ICU-free days (IRR 1.7; 95%-CI: 1.4 to 2.1; p<0.0001) significantly increased in patients under ketogenic diet. There was no difference in 30-day mortality. Analyses indicated favorable changes towards immune homeostasis. Conclusions: Ketogenic diet is a feasible and safe nutritional regimen in septic patients promoting recovery from sepsis-related organ dysfunction and could become a new tool in modern treatment concepts.
2024-06-13 | PXD046061 | Pride