bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative benefit of multiple agents and drug classes for adjuvant therapy (adj rx) of HER2+ early breast cancer (EBC).
Authors: Holmes Frankie Ann , Brammer Melissa , Dubois Renard , Xu Feng , Yao Bin , Lalla Deepa 
Published: May 2019

e12037 Background: Disease-free survival (DFS) in patients with EBC has improved over time. Trials of systemic agents for adj rx of HER2+ BC, including chemotherapies (CT), endocrine, and HER2-targeted agents have reported improved DFS. This review is a high-level overview describing DFS improvements in adj rx HER2+ BC. Methods: Therapeutic agents listed in NCCN guidelines for adj rx HER2+ BC were evaluated for relative and absolute improvements in DFS. Information was derived from US product labels and publications. Hazard ratios, 95% CI, p-values, and DFS differences at 2 and 5 years (if available) are reported. Results: At 2−3 years, adj rx of HER2+ BC with CT and HER2 treatments reported DFS improvements of 4−5% and 0.9−11.3%, respectively. For hormone receptor positive (HR+) BC, unselected by HER2 status, extended adj letrozole had a 1.9% DFS improvement at 2 years; in HR+ HER2+ BC, extended adj neratinib had 4.5% DFS at 2 years. Conclusions: Relative and absolute improvements in DFS in the adj rx BC setting have been largely incremental and cumulative. Absolute improvements in DFS were 0.9−11.3% with CT, HER2 agents, and AIs. In the subset of HR+ / HER2-positive patients, neratinib showed higher DFS improvement compared to non-steroidal AIs. Similar hazard ratios did not always correspond to similar DFS improvements, possibly reflecting differences in baseline risks in the study populations. [Table: see text]
Six cycles of adjuvant anthracycline-taxane-based chemotherapy compared with eight cycles for women with breast cancer.
Authors: Lee Michael , Wilson Sheridan , Porter David James 
Published: May 2019

e12045 Background: 3rd generation adjuvant chemotherapy regimens for breast cancer include FEC every three weeks (Q3W) x 3 cycles and Docetaxel (D) Q3W or weekly paclitaxel (P1W) x 9 weeks (FEC-D/P1W) and AC Q3W x 4 followed by P1W x 12 weeks or D x 4 cycles (AC-P1W). These regimens were developed independently and have not been directly compared. Real world effect of weekly paclitaxel schedule is unknown. Methods: Women with stage 1-3 breast cancer who received 3rd generation adjuvant chemotherapy (with 1 year of adjuvant trastuzumab if HER2+) between 2010-2015 inclusive were identified in the New Zealand Breast Cancer Database. Taxane regimens Q3W D and P1W were grouped for analysis. We compared 5 year overall survival (OS) between shorter FEC-D/P1W (total 6 cycles) and longer AC-P1W or Docetaxel Q3W x 4 cycles (total 8 cycles). Patients who received other taxane schedules or non-standard duration of chemotherapy were excluded. Results: 772 women received the FEC-D/P1W regimen and 488 were treated with AC-P1W. The FEC-D/P1W had more grade II/III disease (96.4% v 93.8%), BMI ≥30 (44.7% v 34.5%), HER2 positive (37.8% v 23.6%) and higher chemotherapy completion rate (95.1% v 83.8%). The AC-P1W cohort had higher nodal positive cases (97.1% v 80.6%). Univariate analysis showed no statistical significance for age, BMI, ethnicity, histological subtype and surgery type but tumour grade, stage and hormone status were significant. We constructed a cohort (n = 926) matched for these factors. After median follow up 27 months, 5yr OS for case matched cohort is 87.4% for FEC-D/P1W v 86.4% for AC-D/P1W (p = 0.825) with HR 0.96 (95%CI 0.67-1.38) in favour of FEC-D/P1W. Conclusions: These results suggest one can de-escalate chemotherapy by using a 6 cycle anthracycline/taxane regimen offering an opportunity to reduce the burden of chemotherapy without compromising survival.
The effects of mindfulness meditation and progressive muscle relaxation on fatigue and quality of life in breast cancer patients receiving adjuvant paclitaxel: A three-arm randomized trial.
Authors: Gok Metin Zehra , Izgu Nur , Karadas Canan , Ozdemir Leyla , Demirci Umut 
Published: May 2019

e12051 Background: Breast cancer patients often suffer from fatigue during adjuvant paclitaxel regimen which frequently impairs quality of life (QOL). Therefore, this three-arm randomized controlled study aimed to examine the effects of mindfulness-based stress reduction (MBSR) and progressive muscle relaxation (PMR) on fatigue and QOL in breast cancer patients receiving adjuvant paclitaxel. Methods: Participants were randomly assigned to either a MBSR (n = 20), (PMR) (n = 19) or control group (CG) (n = 15). Participants in the intervention groups were instructed on MBSR and PGE, the steps of interventions were recorded a voice recorder and a WhatsApp group was designed by the principal investigator. Participants were asked to listen the recorded audio files during exercises. The intervention groups continued MBSR or PMR 20 min. each day, totally 12 weeks at their home. The CG received only an attention placebo education on breast cancer. Data collection tools included Brief Fatigue Inventory (BFI) and Functional Living Index-Cancer (FLIC). Data were collected at three time points: baseline (T1), week 12 (T2), and week 14 (T3) for follow-up assessment. Kruskal Wallis tests was used for data analysis. Results: BFI scores were significantly lower in the MBSR, PMR groups compared with the CG at T2 and at T3 (p < .01). As for FLIC scores, there were no significant differences between the study groups at T2 and at T3 (p > 0.05). Conclusions: A brief, MBSR and PMR initiated concurrently with adjuvant paclitaxel regimen decreased fatigue severity. Based on the results, MBSR and PMR can be recommended as supportive therapies for breast cancer patients receiving adjuvant paclitaxel.
Using tumor genomic profile testing and comorbidity level to personalize chemotherapy decisions among older patients with early-stage breast cancer.
Authors: Chandler Young , Isaacs Claudine , Jayasekera Jinani , Schechter Clyde B. , Cadham Christopher , Mandelblatt Jeanne S. 
Published: May 2019

e12055 Background: Under-representation of women ages 65+ (“older”) in the trials may limit clinical translation of results to this growing population. We used simulation modeling to estimate chemotherapy outcomes by age and comorbidity level among older women with early stage, estrogen-receptor+/HER2- breast cancers with an Oncotype DX score of 26+. Methods: A discrete-time stochastic state-transition model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups of women based on age (65-69, 70-74, 75-79, and 80-89) and comorbidity levels (no/low, moderate, and severe). Age-, comorbidity-specific non-cancer survival was derived from a random 5% sample of women enrolled in the Medicare Part A and B program from 1992 to 2005 and included in the SEER areas. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer and other-cause mortality with chemoendocrine therapy or endocrine therapy alone. Sensitivity analysis tested the impact on outcomes of varying values of uncertain parameters. Results: Women with life expectancies of ≥ 7 years had net gains of 0.17 to 0.45 LYs (2.0-5.4 months) with chemotherapy; this group was mainly women aged 65-69 and 70-74 with no/low or moderate comorbidity. Women destined to develop distant recurrence gained between 4.2-10.4 months. LYs were reduced by chemotherapy toxicity. The majority of women died of other causes, ranging from 59% to 98% across all age groups and comorbidity levels, but chemotherapy reduced breast cancer mortality by 14.5% and 25.7% among women ages 65-69 and 70-74 with no/low comorbidity, respectively. Results were robust in sensitivity analyses, and chemotherapy improved all outcomes as treatment efficacy increased, assuming no change in toxicity. Conclusions: Older women with early stage, estrogen-receptor+/HER2- breast cancers with Oncotype DX scores of 26+ may benefit from chemotherapy, when both conditions of age <75 and comorbidity at no/low or moderate level can be met. Personalized treatment decisions for older women will ultimately depend on comorbidity-specific lifespan and individual preferences for the balance of benefits and harms of chemotherapy.
Circulating tumor cells in patients with locally advanced breast cancer in evaluation of antitumor treatment efficacy.
Authors: Sagakyants Aleksandr B. , Kit Oleg I. , Samaneva Natalia Yu. , Vladimirova Liubov Yu , Shulgina Oksana G. , Ulianova Elena P. , Novikova Inna A. , Mitashok Irina S , Snezhko Tatiana A. 
Published: May 2019

e12064 Background: Circulating tumor cells (CTC) are of great importance in modern cancer research. Biological characteristics of CTC allow using them as tumor markers of high prognostic value. Their quantitative evaluation during treatment can be used to monitor the response to treatment in patients receiving systemic chemotherapy (CT). The purpose of the study was to assess the role of CTC in the prognosis of treatment efficacy in patients with locally advanced Her-2 negative breast cancer. Methods: The study included 42 patients aged 30-65 years with stage IIIA, IIIB, IIIC locally advanced Her-2 negative breast cancer, ECOG-WHO Performance Status from 0 to 2, Karnofsky Performance Status from 100% to 80%. CTC were determined using the CellSearch Veridex System (Johnson & Johnson, USA), taking into account morphological characteristics and expression of epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8, 18 and 19. Results: CTC were found in 86% (36 of 42 patients) before treatment. CTC were not registered in 6 (14%) patients. 1 CTC was detected in 14% (6 patients); 2-3 CTC – 33% (14 patients); more than 3 CTC – 38% (16 patients). 12% (5) patients showed more than 10 CTC, with the maximum of 64 CTC in 1 patient. After 2 cycles of polychemotherapy, CTC were detected in 50% (21 patients). Other 21 patients did not show presence of CTC. Among CTC-positive patients, 1 CTC was detected in 4 patients (19%); from 2 to 3 CTC – in 9 patients (43%); more than 3 CTC – 8 patients (38%). 2 patients (10%) still showed more than 10 CTC – 28 and 33 CTC in the peripheral blood. After 2 cycles of polychemotherapy, the number of patients with more than 1 CTC decreased from 86% to 50%. Polychemotherapy regimen was changed for patients with increasing amounts of CTC. Conclusions: Determination of the CTC number allows evaluation of the treatment efficacy and is a specific marker for the change of applied polychemotherapy for such cancer type.
Ultrasound-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy with clip and activated charcoal in breast cancer patients: A feasibility study.
Authors: Chae Yee Soo , Lee Soo Jung , Lee In Hee , Jung Jin Hyang , Park Ho Yong , Lee Jeeyeon , Kim Won Hwa , Kim Hye Jung 
Published: May 2019

e12067 Background: We report on our experience of ultrasound (US)-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy (NAC) with clip and activated charcoal to guide axillary surgery in breast cancer patients. Methods: Between November 2017 and May 2018, a dual-localization procedure was performed under US guidance for the most suspicious axillary nodes noted at initial staging (before NAC, with clip) and restaging (after NAC, with activated charcoal) in 28 cytologically proven node-positive breast cancer patients. Patients underwent axillary sampling or dissection, which involved removing not only the sentinel nodes (SNs), but also clipped nodes (CNs) and tattooed nodes (TNs). Success (or failure) rates of biopsies of SNs, CNs, and TNs and inter-nodal concordance rates were determined. Sensitivities for the individual and combined biopsies were calculated. Results: SN biopsy failed in four patients (14%), whereas the CN biopsy failed in one patient (4%). All TNs were identified in the surgical field. Concordance rates were 79% for CNs–TNs, 63% for CNs–SNs, and 58% for TNs–SNs. Sensitivity for SN, CN, and TN biopsy was 73%, 67%, and 67%, respectively. Sensitivity was 80% for any combination of biopsies (SN plus CN, SN plus TN, SN plus CN plus TN). Conclusions: US-guided dual-localization of axillary nodes before and after NAC with clip and activated charcoal was a feasible approach that might facilitate more reliable nodal staging with less-invasive strategies in node-positive breast cancer patients.
Accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) in stage 0-II breast cancer: A preliminary report of 57 cases.
Authors: Mark Rufus J. , Gorman Valerie , McCullough Steven 
Published: May 2019

e12068 Background: Randomized trials in Stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial to be equivalent to XRT in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2019, 57 patients have undergone IMRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes ≤ 3 cm, negative surgical margins, and negative sentinel node dissections. IMRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows : V-30 Gy < 105%, Ipsilateral Breast V-15 Gy < 50%, Ipsilateral Lung V-10 Gy < 20%, Contralateral Lung V-5 Gy < 10%, Heart V-3 Gy < 20%, Contralateral Breast Dmax < 2 Gy and Skin Dmax < 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-14 months with a median of 7 months. LR has been 0% (0/57). There were no skin reactions. One patient developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 100% (57/57) of cases. Conclusions: Non-invasive APBI with IMRT targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given with HDR implant. At last follow-up, there have been no LR, skin reactions, or complications. Cosmesis has been excellent in 100% of patients.
HIF1A genetic variability and late adverse events of radiotherapy in breast cancer.
Authors: Marinko Tanja , Goricar Katja , Dolzan Vita 
Published: May 2019

e12069 Background: Hypoxia-inducible factors (HIFs) are transcription factors that play an important part in the regulation of various cell processes involved in carcinogenesis such as cell proliferation, apoptosis, angiogenesis, and metastasis. Additionally, hypoxia could influence response to radiotherapy and radiation was shown to stabilize HIF-1α and affect release of cytokines. Previous studies have already shown that HIF1A genetic variability may modify cancer susceptibility, but data on its influence on treatment response are scarce. As nicotine induces HIF-1α expression, smoking could also modify treatment response. Our aim was to evaluate the association of common functional HIF1A rs11549465 polymorphism and smoking with late adverse events of radiotherapy in breast cancer patients. Methods: Our pilot retrospective study included 92 HER2-positive early breast cancer patients treated with adjuvant radiotherapy between 2005 and 2011. We isolated DNA from buccal swabs and genotyped all patients for HIF1A rs11549465 using competitive allele-specific PCR. Association of polymorphisms with adverse events and interaction with smoking was evaluated using logistic regression. Results: Median follow-up after radiotherapy was 4.2 (2.6-5.5) years. Overall, 30 (32.6%) patients reported late adverse events according to LENT-SOMA criteria, and 11 (12.0%) experienced skin toxicity according to CTCAE v.4.0 (Common Terminology Criteria for Adverse Events). Only 15 (16.3%) of patients were smokers. Minor allele frequency of HIF1A rs11549465 was 0.07. The studied polymorphism was not associated with late adverse events (OR = 0.75, 95% CI = 0.18-3.06, P = 0.688) or late skin toxicity (OR = 0.71, 95% CI = 0.08-6.15, P = 0.756) in our cohort of patients. We also observed no interaction between smoking, HIF1A genetic variability and late adverse events of radiotherapy. Conclusions: HIF1A rs11549465 was not associated with late adverse events of radiotherapy even if smoking was taken into account in our cohort of breast cancer patients.
Automated artificial intelligence quantification of fibroglandular tissue on breast MRI.
Authors: Takhtawala Ruquaiyah , Tapia Negrete Nataly , Shaver Madeleine , Kart Turkay , Zhang Yang , Park Vivian Youngjean , Kim Min Jung , Su Min-Ying , Chow Daniel S. , Chang Peter 
Published: May 2019

e12071 Background: The objective of this study is to examine if a convolutional neural network can be utilized to automate breast fibroglandular tissue segmentation, a risk factor for breast cancer, on MRIs. Methods: This institutional review board approved study assessed retrospectively acquired MRI T1 pre-contrast image data for 238 patients. Ground truth parameters were derived through manual segmentation. A hybrid 3D/2D U-Net architecture was developed for fibroglandular tissue segmentation. The network was trained with T1 pre-contrast MRI data and their corresponding ground-truth labels. The analysis was started with image pre-processing. Each MRI volume was re-sampled and normalized using z-scores. Convolution operations reduced 3D volumes into a 2D slice in the contracting arm of the U-Net architecture. Results: A 5-fold cross validation was performed and the Dice similarity coefficient was used to assess the accuracy of fibroglandular tissue segmentation. Cross-validation results showed that the automated hybrid CNN approach resulted in a Dice similarity coefficient of 0.848 and a Pearson correlation of 0.961 in comparison to the ground-truth for fibroglandular breast tissue segmentation, which demonstrates high accuracy. Conclusions: The results demonstrate significant application of deep learning in accurately automating segmentation of breast fibroglandular tissue.
Influence of radiation therapy on the outcome of T1-2N0M0 triple-negative breast cancer: A SEER population-based retrospective analysis.
Authors: Guan Xiaoxiang , Li Huan , Chen Yajuan , Wang Xin , Tang Lin , Wang Yucai , Shu Yongqian 
Published: May 2019

e12073 Background: For T1-2N0M0 breast cancer after surgery and axillary staging, the current NCCN guideline recommends radiation therapy (RT) after lumpectomy but not total mastectomy unless there is a positive or less than 1 mm negative margin. This recommendation is regardless of hormonal status. Triple-negative breast cancer is a generally considered more aggressive compared with hormone positive breast cancer. We sought to investigate whether there is a survival benefit of RT in T1-2N0M0 TNBC. Methods: A Population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into three groups according to surgery modality and RT: breast conservation therapy (BCT, i.e., lumpectomy + RT), mastectomy alone, and mastectomy + RT. The survival endpoints were breast cancer-specific survival (BCSS) and overall survival (OS), and survival analysis was performed using the Kaplan-Meier method. Results: A total of 22473 female with T1-2N0M0 TNBC diagnosed between 2010 and 2015 were included, with 13395 (60%) T1 and 9078 (40%) T2 cases. Surgery, RT and chemotherapy was done in 21674 (96%), 9633 (43%) and 14651 (65%) patients, respectively. Patients who underwent RT were older ( > 50 years, 78% vs 72%, P< 0.001), had fewer T2 (35% vs 44%, P< 0.001) tumor, and had more chemotherapy utilization (72% vs 60%, P< 0.001). 8807 patients had BCT; 8329 had mastectomy alone and 635 had mastectomy + RT. The 5-year BCSS rate was 94.3% for BCT, 93.3% for mastectomy alone ( P= 0.009 vs BCT), and 83.7% for mastectomy + RT ( P< 0.001 vs BCT and P< 0.001 vs mastectomy alone), respectively. The 5-year OS rate was 88.6% for BCT, 83.0 % for mastectomy alone ( P< 0.001 vs BCT), and 79.6% for mastectomy + RT ( P< 0.001 vs BCT and P= 0.190 vs mastectomy alone), respectively. Conclusions: In patients with T1-2N0M0 TNBC, BCT was associated with superior BCSS and OS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT, with worse BCSS and similar OS.
Comparing the American Joint Committee on Cancer (AJCC) breast cancer staging eighth versus seventh edition and breast cancer biology in large databases.
Authors: Young Jessica S. , Takabe Kazuaki , Asaoka Mariko , Edge Stephen B. 
Published: May 2019

e12077 Background: The AJCC 8th edition Breast Cancer Staging system includes biomarkers (estrogen receptor, progesterone receptor, Her2), grade and a genomic assay, to better reflect outcomes, compared to the 7th edition. We used databases with anatomic, biomarker and genomic information to determine if the 8th edition reflects biology better than the 7th edition. Methods: 696 breast cancer patients in The Cancer Genome Atlas (TCGA) and Text Information Extraction System (TIES) were staged both with 7th and 8th edition. Results: From the 7th to 8th editions, 66% of stage 2 patients migrated (64% to stage 1, 1.5% to stage 3). 36% of stage 3 patients migrated (22% to stage 1, 13% to stage 2). We analyzed the differences between stage 1 and 2 in both editions, and the overall survival hazard ratio calculated using Cox regression was greater in the 8th edition than the 7th (HR=1.50, HR=1.22 respectively). We performed Gene Set Enrichment Analysis (GSEA) and found that gene sets related to cell cycle and cell proliferation (E2F targets, G2M checkpoint) were significantly enriched in higher stage in 8th edition but not 7th. Mutant Allele Tumor Heterogeneity (MATH) and Homologous Recombination Defects (HRD) were elevated in higher stages in the 8th edition (p=0.022, p<0.001 respectively), but not the 7th. Immune cells (CD8 Tcell, NK cell) as well as CYT (Immune cytolytic activity score), and Tcell exhaustion markers (PD1, PDL1) were all found to be elevated in higher stage in 8th edition, but not 7th. Conclusions: The 8th edition AJCC Breast Cancer Staging system categorizes cancers by aggressive biology better than the 7th edition. We also found that higher stage tumors trigger an enhanced immune response, but are unable to overcome the aggressive cancer biology.