bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant endocrine monotherapy (ET) versus adjuvant breast radiation (RT) alone in healthy older women with stage I, estrogen receptor-positive (ER+) breast cancer: An analysis of the National Cancer Database (NCDB).
Authors: Bui Anthony H. , Chadha Manjeet , Shao Theresa H. , Gerber Naamit K. , Cate Sarah P. , Boolbol Susan K. , Zubizarreta Nicole J. 
Published: May 2019

519 Background: The NCCN guidelines state that breast RT may be omitted in patients > 70 years of age with ER+, clinically node-negative, T1 breast cancer (BC) who receive adjuvant ET. Available data on older patients notes that local relapses are the most frequent site of failure, and distant relapse rates are low. The side effects of ET are not inconsequential and negatively affect QOL. The objectives of this study are to examine clinical outcomes including overall survival (OS) in women ≥70 years of age treated by lumpectomy(L)+ET and L+RT in the NCDB. Methods: The 2004-2013 NCDB includes 76,431 women ≥70 years with ER+ stage I BC who underwent L, and had a minimum one year follow up. Women who received no adjuvant therapy, both ET+RT, or any chemotherapy were excluded. To limit the analysis to healthy women, we excluded subjects with a Charlson comorbidity index > 0. We identified 24,572 patients who received either adjuvant ET monotherapy or adjuvant RT alone. Among these, 46% (11,313) received ET and 54% (13,259) breast RT. Overall median follow up was 57 months (range: 12-143 months). Analysis of OS between the 2 treatment groups was performed using Kaplan-Meier statistics and Cox proportional hazards regression; propensity weighting was used to balance covariates across the 2 treatment groups. Results: After propensity weighting, demographic covariates including age, race, insurance, and facility type were balanced between the 2 treatment groups. The median OS for ET was 125.9 months (95% CI 120.1-131.8), and 127.2 months for RT (95% CI 124.5-131.7) (p < 0.0001). The weighted hazard of death was 11.7% less in women receiving RT compared to ET (HR 0.883, 95% CI 0.834-0.936, p < 0.0001). Conclusions: To our knowledge, this is the first large study comparing RT and ET monotherapy in healthy older women with stage I, ER+ BC. The OS with RT alone is not inferior to ET alone, and in this study population is noted to be better. While this analysis has various limitations not dissimilar from other NCDB database studies, our observations are encouraging and warrant further research with prospective studies.
Low-fat dietary pattern and long-term breast cancer incidence and mortality: The Women’s Health Initiative randomized clinical trial.
Authors: Chlebowski Rowan T. , Aragaki Aaron K , Anderson Garnet L , Pan Kathy , Neuhouser Marian L , Manson JoAnn E , Thomson Cynthia A. , Mossavar-Rahmani Yasmin , Lane Dorothy , Johnson Karen , Wactawski-Wende Jean , Linda Snetselaar , Rohan Thomas E , Luo Juhua , Barac Ana , Prentice Ross L 
Published: May 2019

520 Background: Observational studies of dietary fat intake and breast cancer have inconsistent findings. To address this issue, the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial assessed a low-fat dietary pattern influence on breast cancer incidence and outcome. Methods: The WHI DM trial is a randomized, controlled clinical trial conducted at 40 US centers, where 48,835 postmenopausal women, aged 50-79 years, with no previous breast cancer and dietary fat intake ≥32% of total energy, were randomly assigned, from 1993-1998, to a usual diet comparison group (60%) or dietary intervention group (40%) with goals to reduce fat intake to 20% of energy and increase vegetables, fruit, and grain intake. This study is registered as: NCT00000611. Results: The dietary intervention significantly reduced fat intake; increased fruit, vegetable and grain intake with modest weight loss (3%) (all P< 0.001). During 8.5 years of dietary intervention, there were 8% fewer breast cancers and deaths from breast cancer were somewhat lower in the intervention group but the rates were not significantly different. However, deaths after breast cancer (breast cancer followed by death from any cause) were significantly reduced in the intervention group, both during intervention (hazard ratio [HR] 0·65 95% confidence interval [CI] 0·45-0·95) and through 16.1 year (median) cumulative follow-up. Now, after long- term, cumulative 19.6 year (median) follow-up, with 3,374 incident breast cancers, the significant reduction in deaths after breast cancer continued (with 1,011 deaths, HR 0·85 95% CI 0·74-0·96) and a significant reduction in deaths from breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (with 383 deaths, HR 0·79 95% CI 0·64-0·97). Conclusions: Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, significantly reduced the risk of death from breast cancer in postmenopausal women. To our review, these findings provide the first randomized clinical trial evidence that a dietary change can reduce a postmenopausal woman’s risk of dying from breast cancer. Clinical trial information: NCT00000611.
Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.
Authors: Stewart Paul , Blanchette Phillip S. , Shah Prakesh S , Ye Xiang Y , Boldt R Gabriel , Fernandes Ricardo , Vandenberg Theodore A. , Raphael Jacques 
Published: May 2019

522 Background: One year of adjuvant trastuzumab (T) remains the standard treatment for patients with HER2 positive breast cancer. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant T were not consistent, particularly with the PERSEPHONE and the final PHARE and Short-HER trials’ results. Our objective was to conduct a systematic review and meta-analysis of randomized trials in patients with HER2 positive breast cancer to assess whether a shorter duration of adjuvant T was non-inferior to one year of treatment. Methods: PubMed, EMBASE and The Cochrane Library were searched for eligible randomized trials. Hazard ratios (HR) for disease free and overall survival (DFS, OS) were weighted using generic inverse variance and pooled in a meta-analysis using random-effects models. The median of non-inferiority margins derived from each trial was calculated to set a non-inferiority margin of 1.29 for the pooled analysis. Subgroup analyses compared survival outcomes by estrogen receptor (ER) status, nodal status, length and timing of trastuzumab treatment. Results: Data of 11,376 patients from 5 trials were analyzed. A shorter duration of T was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but worse for OS (HR 1.16, 95%CI 1.01-1.32). In addition, the non-inferiority for DFS was met for patients with ER positive disease (HR 1.1, 95%CI 0.95-1.28) and patients treated with 6 months (HR 1.09, 95%CI 0.98-1.22) or sequential T (HR 0.97, 95%CI 0.75-1.27). Conversely, the non-inferiority for DFS was not met for patients with ER negative disease (HR 1.22, 95%CI 1.06-1.41), patients treated with 9 weeks (HR 1.26, 95%CI 1.02-1.55) or concomitant T (HR 1.25, 95%CI 1.07-1.45) and patients with node negative (HR 1.12, 95% 0.93-1.35) or positive (HR 1.16, 95%CI 0.99-1.36) disease. Conclusions: Within the limitations of the available data and the different non-inferiority margins used in randomized trials, a shorter duration of adjuvant T is non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer, particularly in patients with ER positive disease. Further trials with appropriately chosen non-inferiority margins are needed to confirm the optimal duration of T in patients with low-risk disease.
Simulation modeling of the effects of adjuvant chemotherapy in early-stage breast cancer.
Authors: Jayasekera Jinani , Schechter Clyde B. , Sparano Joseph A. , Isaacs Claudine , Gray Robert James , Cadham Christopher , Mandelblatt Jeanne S. 
Published: May 2019

526 Background: The recent Trial Assigning Individualized Options for Treatment (TAILORx) was practice changing. However, several important questions remain unanswered about therapy for women with early stage, hormone receptor positive (HR+), HER2- breast cancers, including chemotherapy effects by age and different Oncotype recurrence score (RS) cut-points, and longer follow-up. We developed a simulation model to extend the trial results to begin to fill these gaps. Methods: We developed a simulation model using an empirical Bayesian approach to simulate women eligible for the TAILORx trial. The joint distributions of patient and tumor characteristics were derived from de-identified TAILORx data. The remaining inputs used data independent of the trial, including SEER, the Oxford Overview, and other trials. TAILORx was simulated to examine the effects of chemotherapy (+ hormonal Rx) vs. hormonal Rx alone on distant recurrence-free survival (DRFS) at 9- and 20-years by age (≤50 and >50 years) and RS (11-25 and 16-25). We also evaluated the effects of chemotherapy in women with RS 26-30. Hazard ratios (HR) were determined using Cox regressions and DRFS by treatment were derived from Kaplan-Meier curves. We report the mean results from 1000 trial simulations, where each simulation randomly sampled values for each parameter from their observed joint distribution. Finally, the original trial was replicated for model validation. Results: The model closely replicated actual trial results. Sample sizes ranged from 7000-10000. The model estimated that chemotherapy improved DFRS in women aged ≤50 with RS 16-25 (Table). The 20-year event rates remained low in the 11-25 category. Among women with RS 26-30, HR for no chemo vs. chemo was 1.38 (95% CI:1.18-1.58). Conclusions: Simulation suggests that chemotherapy may reduce distant recurrence in younger women at different cut points between 11-25. Simulation modeling may be useful to translate trial results to broader population subgroups than those possible to test in RCTs. Nine-year distant recurrence-free survival by chemotherapy. [Table: see text]
Prognostic value of a new clinical-genomic model to predict 10-year risk of recurrence in patients with operable breast cancer.
Authors: Lei Lei , Huang Tzu-Ting , Chen Andre Ching-Hsuan , Lu Tzu-Pin , Cheng Skye Hung-Chun 
Published: May 2019

530 Background: Searching for a specific biomarker to predict long-term risk of recurrence for all breast cancer subtypes is challenging. DGM-CM6 (Distant Genetic Model-Clinical variable Model 6) is a new clinical-genomic prognostic model developed from the 18-gene panel which was reported previously. This study aims to validate the long-term prognostic value of this new model in all subtypes of operable breast cancer patients. Methods: We included 752 operable breast cancer patients with stage I-III in all subtypes treated in a Cancer Center from 2005 to 2014 as the internal validation (IV) cohort. The median follow-up was 94.1 months. Meanwhile, Affymetrix U133P2 (n = 1139) data obtained from GEO (GSE9195/16391/17907/19615/20711/21653/42568, EMTAB365) were collected as the external validation (EV) dataset. The prognostic effect of DGM-CM6 was then evaluated by uni- and multivariate analyses. The low- and high-risk patients ( < 33 or ≥ 33 as cut-off value) classified by DGM-CM6 were evaluated by the 10-year distant relapse-free interval (DRFI), relapse-free interval (RFI), relapse-free survival (RFS) and distant relapse-free survival (DRFS), respectively. We further compared the predictive performance between DGM-CM6/DGM and PAM50-ROR score in our IV dataset. Results: In the IV dataset, DGM-CM6 was proved to be an independent prognostic factor by multivariate analysis with hazard ratios of 3.1 (1.6-6.0) for RFS (P = 0.0009) and 3.2 (1.6-6.3) for DRFS (P = 0.0009). Significant differences were observed between low- and high-risk groups with 10-year RFI (94.0% vs. 83.5%, P < 0.0001), RFS (90.0% vs. 80.5%, P = 0.0003), DRFI (94.1% vs. 85.0%, P < 0.0001), and DRFS (90.1% vs. 81.9%, P = 0.0004), respectively. The prognostic value of RFS was convinced in the EV dataset (HR = 1.34, P = 0.00052) by the DGM only. According to C-index estimate analysis, DGM appeared to have better performance comparing with PAM50 ROR score in prediction of long-term DR, DRFS, RFI, and RFS in N0 patients (C index for distant recurrence: 0.582 by DGM, 0.528 by ROR). Conclusions: DGM-CM6 could be a new long-term prognostic model to be applied in all subtypes of operable breast cancer patients. Further validation in a large scale of clinical trials is needed.
Abandonment trajectories of conventionally fractionated adjuvant radiotherapy in breast cancer care.
Authors: Xu Xiao , Soulos Pamela R. , Herrin Jeph , Wang Shi-Yi , Pollack Craig Evan , Evans Suzanne B. , Gross Cary Philip , Yu James B. 
Published: May 2019

531 Background: Hypofractionated radiotherapy is the recommended approach for adjuvant breast cancer care. Yet physicians have been slow to abandon conventionally fractionated radiotherapy (CFRT). We examined distinct trajectories of abandoning CFRT among physician patient-sharing peer groups and the associated cost implications. Methods: Using 2011-2014 national Medicare claims, we constructed peer groups of physicians (radiation and medical oncologists, surgeons, and primary care physicians) who cared for women with breast cancer. Women ≥66 years of age who underwent lumpectomy plus adjuvant radiotherapy were included. Peer groups represented physicians who frequently shared patients with one another. For each peer group, we calculated risk-adjusted rate of CFRT use in 2011-2012 (T1) and 2013-2014 (T2) after accounting for patient risk factors. Based on these utilization rates and a latent growth curve analysis, we identified distinct trajectories of abandoning CFRT among peer groups and estimated their cost implications from the Medicare perspective. Results: The 215 physician peer groups (caring for 16,988 patients) exhibited four distinct trajectories of CFRT use: 1) persistent high use (mean adjusted utilization: T1 = 94.3%, T2 = 90.6%); 2) decreased high use (T1 = 81.3%, T2 = 65.3%); 3) decreased medium use (T1 = 60.1%, T2 = 44.0%); and 4) decreased low use (T1 = 31.6%, T2 = 23.6%). They accounted for 33.0%, 35.3%, 25.6% and 6.0% of the peer groups, respectively. Compared to “persistent high use” of CFRT, peer groups with “decreased high use” and “decreased medium use” of CFRT had a smaller proportion of patients receiving radiotherapy at free-standing (vs. hospital-based) facilities (adjusted odds ratio = 0.89, p = 0.01; and 0.78, p < 0.01; respectively). Accelerating abandonment of CFRT in the three higher utilization trajectories to “decreased low use” for the 2011-2014 patient cohort could save Medicare $342.7 million (95% confidence interval: $232.2-$457.6 million). Conclusions: Physician peer groups had distinct trajectories in abandoning CFRT exhibiting different baseline levels and rates of change in utilization. Efforts to reduce overuse of CFRT could generate substantial savings.
Breast Cancer Index and risk stratification in luminal subtypes: A trans-ATAC study.
Authors: Sestak Ivana , Zhang Yi , Schnabel Catherine A. , Cuzick Jack M. , Dowsett Mitchell 
Published: May 2019

534 Background: The Breast Cancer Index (BCI) is a gene-expression based signature that provides prognostic information for overall (0-10 years) and late (5-10 years) distant recurrence (DR) and prediction of extended endocrine benefit in hormone receptor positive (HR+) early stage breast cancer. The current analysis aims to further characterize, correlate and compare the prognostic performance of BCI in luminal subtypes based on immunohistochemical classification. Methods: 670 postmenopausal women with HR+, LN- disease from the TransATAC cohort were included in this analysis. Luminal A-like tumors (LumA) were identified as those with ER+ and/or PR+ and HER2 -, and Ki67 < 20% by IHC. All other tumors were classified as Luminal B-like (LumB) for this analysis. Primary endpoint was DR. Cox regression models were used to examine BCI prognostic performance according to luminal subtype, adjusting for the clinicopathological model Clinical Treatment Score (CTS). Results: 452 (67.5%) patients were classified as LumA and 218 (32.5%) as LumB. BCI was highly prognostic in LumA cancers (adjusted HR = 1.57 (1.23-1.96), P < 0.001, ΔLR-χ2= 14.09), but not in LumB tumors (adjusted HR = 1.20 (0.94-1.52, P = 0.14, ΔLR-χ2= 2.23). In LumA, 10-year DR risks in BCI intermediate and high risk groups were very similar (25.6% (16.4-38.6) and 25.3% (13.5-44.3), respectively) and significantly different from BCI low (3.9% (2.1-7.0); HR = 7.47 (3.50-15.96) and HR = 8.13 (3.27-20.23), respectively). In LumB, 10-year DR risks in BCI low and BCI intermediate risk groups (13.8% (6.8-26.9) and 14.6% (8.3-24.9), respectively) were very similar and significantly lower than for the BCI high (29.1% (20.0-41.1)). Lum subtyping was only prognostic in the BCI low risk group (LumA vs. LumB: HR = 4.27 (1.65-11.02)) but not in the other two BCI risk groups. Conclusions: BCI provided significant prognostic information in Lum A subtype. These results show that BCI intermediate and high risk had similar risk of DR in LumA tumors, while shared similarly low risk of DR as BCI-low in LumB tumors. Further evaluation is needed to elucidate the distinct mechanisms underlying each classification system.
Adjuvant chemotherapy in small node-negative triple-negative breast cancer (TNBC).
Authors: Steenbruggen Tessa Gerjanne , Van Ramshorst Mette S. , van Werkhoven Erik , Dezentjé Vincent O. , Siesling Sabine , Linn Sabine C. , Sonke Gabe S. 
Published: May 2019

536 Background: International guidelines differ in their recommendation for adjuvant chemotherapy in small node negative TNBC. We evaluated associations of chemotherapy with long-term outcome in a large population-based TNBC cohort. Methods: All patients diagnosed with pT1N0M0 TNBC between 2005 and 2015 were identified from the Netherlands Cancer Registry. Patient, tumor and therapy characteristics were recorded. Date and cause of death were obtained from Statistics Netherlands. We used multivariable cox regression models to evaluate associations of chemotherapy with overall survival (OS) and breast-cancer specific survival (BCSS), adjusted for baseline characteristics. Subgroup analyses were performed by tumor size and grade. Results: We identified 4393 patients: 284 with T1a, 924 with T1b, and 3185 with T1c tumors. Chemotherapy was administered in 53% of patients: 6% with T1a, 17% with T1b and 67% with T1c. Chemotherapy use increased over time and varied by geographic region. Patients receiving chemotherapy were younger, had larger tumors, higher tumor grade, and more often isolated tumor cells (itc) in the lymph nodes. At a median follow-up of 7 years (IQR 5-10 years), 611 patients had died, of whom 287 due to breast cancer. Chemotherapy was associated with improved OS in the whole group (adjusted hazard ratio [aHR] 0.55; 95% CI 0.44–0.69), in the pT1c subgroup (aHR 0.53, 95% CI 0.41-0.67), and in grade 3 tumors (aHR 0.50, 95% CI 0.39-0.65). Associations were not significant for pT1ab or grade 1-2 tumors (table). Findings for BCSS were in line with OS results (table). To illustrate the absolute difference we estimated 10-year OS and BCSS for a 60-year old woman with a pT1cN0(itc+) grade 3 TNBC. The predicted 10-year OS was 67% with chemotherapy and 49% without; predictions for 10-year BCSS were 80% and 66%, respectively. Conclusions: Adjuvant chemotherapy is associated with higher OS and BCSS in small node negative TNBC. Benefit is most evident in grade 3 tumors and tumors > 1cm and not evident in tumors ≤1cm and grade 1-2.[Table: see text]
Eflapegrastim, a novel and potent long-acting GCSF for reducing chemotherapy-induced neutropenia: Integrated results from two phase III trials in breast cancer patients.
Authors: Schwartzberg Lee S. , Bhat Gajanan , Bharadwaj Jayaram S. , Hlalah Osama , Restrepo Alvaro , Mehmi Inderjit , Chawla Shanta , Cobb Patrick Wayne 
Published: May 2019

539 Background: Eflapegrastim (E) is a novel long-acting GCSF comprised of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a PEG linker (MW, 72 kDa). E showed increased potency vs pegfilgrastim (P) in preclinical and Phase I and II trials. Two identically designed Phase III pivotal trials (NCT02643420, NCT02953340) were conducted globally with a fixed dose of 13.2 mg E containing 3.6 mg GCSF to evaluate E vs P (6 mg) in pts receiving chemotherapy for early-stage breast cancer. Methods: Each open-label trial randomized pts 1:1 to a single subcutaneous dose of E 13.2 mg/0.6 mL or P 6 mg/0.6 mL on Day 2 of each of four 21-day cycles following Day 1 adj/neoadj docetaxel 75 mg/m2 + cyclophosphamide 600mg/m2 (TC). The primary endpoint was to demonstrate E non-inferiority (NI) to P as measured by mean duration of severe neutropenia (DSN) in Cycle 1. Results: A total 643 intent-to-treat pts (314 E/329 P) with median age 60 yrs (24–88) were enrolled. Cycle 1 mean (SD) DSN was 0.24 (0.581) vs 0.36 (0.789) days for E and P, confirming NI (p < .0001) and suggesting statistical superiority (p < .029). DSN NI was also shown across cycles 2–4. Among subgroups, including elderly (≥65 yrs) and overweight ( > 75kg) pts, DSN was reduced for E vs P. In Cycle 1, E showed an absolute risk reduction for severe neutropenia of 6.5% vs P (27.1% relative risk reduction, p < .043). Neutropenic complications (hospitalization and/or anti-infective use) were 2.9% and 4.0% for E and P (p = ns). Incidence of FN was low for both E and P, 1.6% vs 1.8% in Cycle 1 and 3.2% vs 3.0% overall. ANC profiles showed sustained increased levels for E vs P in the recovery phase across all cycles. Safety profiles were similar for E and P, including primarily for expected hematologic AEs and for bone pain and other musculoskeletal pain. Conclusions: These integrated pivotal trial results confirm a similar safety profile and non-inferiority in reducing neutropenic risk for E at a lower GCSF dose vs P. The data also suggests the potential for increased potency of E to deliver improved clinical benefit, a possibility that warrants further clinical trials. Clinical trial information: NCT02643420, NCT02953340.