bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of diabetes and prediabetes unmasked by dexamethasone in women undergoing (neo) adjuvant taxane therapy.
Authors: Mahinbakht Dana , Lavasani Sayeh Moazami , Yu Wai (Kim) , Samoa Raynald , Ruel Nora , Mortimer Joanne E. 
Published: May 2020

e12526 Background: Women with early stage breast cancer receive premedication with dexamethasone prior to administration of paclitaxel and docetaxel. We undertook a retrospective chart review to determine the frequency of steroid-induced hyperglycemia in women receiving steroid premedication with paclitaxel and docetaxel. Methods: Women who were receiving paclitaxel or taxotere chemotherapy as (neo)adjuvant therapy were identified from pharmacy records. Patients were excluded if they were currently receiving insulin or hypoglycemic agents for diabetes. A Comprehensive Metabolic Panel (CMP) was performed prior to chemotherapy and the random glucose level was recorded. The highest random glucose level recorded during all cycles of treatment was used in the analysis. The threshold for diabetes is a random glucose of 200 mg/dL and levels > 150 mg/dL, but less than 200 mg/dL is considered prediabetes. Between August 2017 to December 2019, 131 patients were identified and 100 met the criteria for inclusion. The study was approved by the Institutional Review Board. A single individual abstracted the data which included demographic data, BMI, comorbidities, random glucose levels prior to therapy and whether they received treatment for the elevations in blood glucose. Results: A total of 131 charts were reviewed, but 31 were excluded because 2 were male, 13 had type 2 diabetes at diagnosis, and 16 had metastatic disease. The median age of the 100 patients was 53 years (range 31 to 82 years); 45% were White/Non-Hispanic, 28% Hispanic, 18% Asian, 5% African American, 1% were Native Hawaiian or other Pacific Islander, 2% were unknown, and 1% were of mixed race. Prediabetic random glucose levels were recorded in 30% of patients and 23% had levels consistent with a diagnosis of diabetes. Out of the patients who exhibited a blood glucose above 200, 16 out of the 23 patients were White, 6 of them were Hispanic and 1 was Asian. The average BMI was 27.7. The average BMI of patients who exhibited a blood glucose of over 200 mg/dL was 28.85 and the average of those who had a blood glucose of over 150 mg/dL was 27.56. Conclusions: Diabetes and prediabetes were unmasked by taking the premedication with dexamethasone in 53% of women undergoing (neo)adjuvant docetaxel or paclitaxel. Current guidelines do not recommend additional blood work after completion of active treatment. Given our results, it is important that medical oncologist ensure that patients with elevations in random glucose be referred for appropriate endocrine workup and therapy, including lifestyle modifications.
Assessment of the risk of tumor progression in different subtypes of breast cancer.
Authors: Vladimirova Liubov Yu , Frantsiyants Elena M. , Samaneva Natalia Yu. , Storozhakova Anna E. , Bandovkina Valeria A. , Cheryarina Natalia D. , Sheiko Elena A. , Sergeeva Marina M. , Kit Oleg I. , Lisutin Aleksandr E. , Nepomnyashchaya Evgeniya M. 
Published: May 2020

e12551 Background: Breast cancer (BC) is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the risk of tumor progression in breast cancer after 2 chemotherapy cycles are required. The purpose of the study was to analyze blood levels of TGFβ, TGFR2, TNF, TNFα, TNFR1, TNFR2, MMP-9 and CD-44 in patients with various BC subtypes before and after 2 chemotherapy cycles. Methods: The study included 42 patients with various BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of TGFβ, TGFR2, TNF, TNFR1, TNFR2, CD-44, MMP-9 were measured by ELISA in the blood of all patients prior to anticancer therapy and after 2 chemotherapy cycles. Statistical processing of results was performed using the Statistika 6.0 software by the Student’s t-test. Results: Levels of TGFβ, TGFR2, TNF, TNFα, TNFR1, TNFR2, CD-44, MMP-9 in patients with all BC subtypes were high before the treatment. After 2 chemotherapy cycles, the values decreased statistically significantly in all BC subtypes: CD-44 decreased by 25.2%, 30% and 54.7% in luminal A, luminal B and TNBC, respectively; TNFα – by 26.2%, 48.3% and 50.8%, respectively; TNFα-R1 – by 52.1%, 39.2% and 50.3% respectively; TNFα-R2 – by 31.7%, 32.8% and 41.9% respectively; MMP-9 – 35.3%, 32.6% and 43.3% respectively. The patients remained in remission for 3 years. When the levels were high or did not differ from initial values, the tumor progressed. Conclusions: We identified a set of criteria allowing with high probability to determine the growth and progression of tumors in various subtypes of breast cancer after two cycles of chemotherapy. A decrease in the levels of TGF-β, TNF, MMP-9, and CD-44 demonstrates remission; stabilization or increase of these indicators leads to further early progression of the disease.
Evaluation of prognostic significance of microRNA in tumors of luminal, primary operable breast cancer without Her2 neu overexpression in postmenopausal women.
Authors: Ulianova Elena P. , Tokmakov Vasilij V. , Shatova Iuliana S. , Sagakyants Aleksandr B. , Goncharova Anna S. , Zaikina Ekaterina V. , Chernikova Elena N. , Bakulina Svetlana M. , Pushkareva Tatiana F. , Kit Oleg I. , Lisutin Aleksandr E. 
Published: May 2020

e12558 Background: Breast cancer (BC) is associated with miRNAs, the qualitative and quantitative analysis of which shows significant differences between molecular subtypes, as well as between miRNAs circulating in the bloodstream and detected in tumor tissue. Since there is no clear characteristics for markers of luminal B primary operable BC without Her 2 neu overexpression, our purpose was an evaluation of prognostic significance of miRNA-21, 221, 20a, 200a, 196a in such postmenopausal patients in order to create a diagnostic panel. Methods: The study included 120 samples of healthy tissues of patients with luminal A BC (group 1, mean age 76.16±3.14 years) and tumor tissues of patients with luminal B BC (group 2, mean age 69.5±3.2 years); invasive ductal carcinoma in all patients. The expression status was analyzed using 5 mioRNA markers associated, according to the literature, with various molecular subtypes of BC (miRNA-21, 221, 20a, 200a, 196a). The Thermo Scientific PureLink RNA Mini Kit was used for the total RNA isolation. The reverse transcription reaction was performed using the ImProm-II Reverse Transcriptase kit (Promega). The Livak/2 method was used to assess the relative expression of miRNAs. Results: The average relative expression was: miRNA-21 in group 1 – 0.2±0.01, group 2 – 1.5±0.05; miRNA- 221 in group 1 – 0.19±0.02, group 2 – 0.43±0.04; miRNA -20a in group 1 – 0.12±0.01, group 2 – 0.13±0.01, miRNA -200a in group 1 – 0.22±0.02, group 2 – 0.96±0.06; miRNA- 196a in group 1 – 1.06±0.02, group 2 – 1.56±0.04. The differences between the groups were statistically significant (p = 0.0001); the difference was statistically insignificant only for miRNA -20a (p = 0.159955). Conclusions: Results of the study allow considering the overexpression of miR-21, 221, 200a and 196a and the relatively low expression of miR-20a as diagnostic markers for a diagnostic panel for luminal B BC without overexpression of HER2/neu.
Prognostic factors impacting survival in early HER2-positive breast cancer (BC): Results from a 1,142 patients database study.
Authors: Hegg Roberto , Mattar Andre , Rocha Maurício , Oliveira Renato Watanabe , Julian Guilherme Silva , Gebrim Luiz Henrique 
Published: May 2020

e12561 Background: early systemic therapy has reduced recurrence and mortality from BC, especially among HER2+ subtype. Despite these advances, the difficulty of developing countries in incorporating new treatments, as well as the molecular and phenotypic profiles of HER2+ BC, are associated with the heterogeneity of treatment responses, leading to poor prognosis and outcomes. However, real-world data on prognostic factors for early HER2+ BC patients are scarce, especially in the Brazilian context. Therefore, this study aims to evaluate the influence of prognostic factors on disease-free survival (DFS) and overall survival (OS) in early HER2+ BC patients. Methods: this retrospective study identified early HER2+ BC (stage I to III with positive immunohistochemistry and in-situ hybridization) patients from Pérola Byington’s public hospital database (São Paulo, Brazil) diagnosed between January 2010 to March 2018. Patients were excluded if they were less than 18 years old, participated in clinical trials, presented metastatic disease de novo, concurrent malignancy, or inconsistent data. Multivariate Cox regression was used to evaluate prognostic factors for survival, and OS and DFS were estimated by Kaplan-Meier analyses. Results: of the 1,625 patients identified in the database, 1,142 women were included in the study. Of those, 40% were diagnosed with less than 50 years old. Among the included patients, 40.3% were HR-/HER2+ and 59.7% were HR+/HER2+. In addition, 19.4% of patients were diagnosed at stage I, 42.9% at stage II and 37.7% at stage III. A total of 1033 patients were included in the DFS analysis, with a probability of 71.8% DFS in 5-years. For OS analysis, a probability of 75.4% OS in 5-years was observed for 1139 patients included. The multivariate analysis showed that tumor staging, lymph node involvement and pathological complete response (pCR) were independent prognostic factors for both DFS and OS. Conclusions: the study in the Brazilian cohort corroborates the literature, showing that tumor staging, pCR, and lymph node involvement are key markers for DFS and OS and they should be considered when managing the early HER2+ BC patients. [Table: see text]
Loss of Her-2 expression after neo-adjuvant therapy with dual anti-Her-2 agents (Pertuzumab/Herceptin) with chemotherapy in locally advanced Her-2 positive breast cancer.
Authors: Gupta Niraj K. , Giblin Erica , Spivey Tara , Govert Kristen , Leagre Christopher A. , Liebross Robert H. , Schmidt Kristen , Heckman Patrick , Burnett Riessa , Yadav Rina , Tutterrow Rachelle , Beaudrie Nick , Durk Jessic , Tumati Vasu , Dugan Thomas , Paul Robert , Sando Ian , Donnelly Jamie ,   St. Vincent Cancer Care
Published: May 2020

e12562 Background: Conversion of Her-2 positive to negative after neoadjuvant treatments in Her-2 positive breast cancer has been reported. In most of these reports either chemotherapy alone or in combination with a single Her-2 agent (trastuzumab) was utilized. Use of dual anti-Her-2 agents (Pertzummab/Trastuzumab) along with chemotherapy as the neoadjuvant treatment regimen in Her-2 + breast cancer is a standard of care now. We looked at the loss of Her-2 expression after neo-adjuvant regimen consisting of dual anti-Her-2 agents and chemotherapy in locally advanced Her-2 + breast cancer. Methods: We reviewed the records of Her-2 positive patients with T2 or higher or lymph Node+ Her-2 + breast treated at our institution. Patients who had received neo-adjuvant chemotherapy and dual anti-Her-2 agents, pertuzumab and Trastuzumab were identified for this study. Clinical and pathologic data was collected. Her-2 expression was determined by IHC and FISH. Results: Between Dec 2014 and June 2019, 79 patients for identified. Median age was 47 yrs, range 31-83 yrs. All were females except one. Pre-treatment, 74 pts. were 3 + on IHC and 5 pts. were 2+ on IHC, but positive by FISH. Median Her-2/CEP 17 copy number ratio was 6.2, range 3.6-16.7. Sixty patients were ER positive and 19 were ER negative. Pertuzumab+ TCH was the most common regimen used, 91% of the patients. All patients underwent surgery. Forty five out of 79 patients, 56%, had a pCR. Thirty four pts with residual disease were re-assessed for Her-2 expression. 7/32 (20.5%) patients were Her-2 negative. 6/7 pts. were 0/1+ by IHC and 1 pt. was 2+ by IHC but negative by FISH. Five out of seven pts. (71.5%) converting to Her-2 negative were ER negative at diagnosis and 2/7 (28.5%) converting to Her-2 negative were ER + at diagnosis. All patients converting to Her-2 negative had received Pertuzumab+TCH. Conclusions: Loss of Her-2 expression is observed after neoadjuvant treatments with a dual anti-Her-2 regimen along with chemotherapy. Implications of this change on choosing adjuvant treatments in Her-2 + pts who have had neo-adjuvant therapy and effect on recurrence/survival outcomes needs to be explored in larger studies.
Increased favorability of small breast cancers.
Authors: Maeda Shigeto , Yamanouchi Kosho , Hirayama Takanori , Kobayashi Shinichiro , Tokunag Hiroyuki , Takeshita Hiroaki , Miura Shiro , Ito Masahiro , Kuroki Tamotsu 
Published: May 2020

e12576 Background: Breast cancer is classified into three prognostic groups based on the following biologic factors: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and nuclear grade (NG). According to this classification, we determined the biological behavior in order to understand if a small breast cancer is biologically more favorable than a large one (T1-2 breast cancers). Methods: The inclusion criteria for this study were (1) presence of T1-2 breast cancer measurable by magnetic resonance imaging (MRI) or ultrasound(US), and (2) availability for determination of ER, PR, and NG histological status. Inflammatory breast cancer, male breast cancer, tumors of unknown size on MRI or US, and complications due to other cancers were excluded from this study. From April 2007 to December 2019, 1173 patients with surgically proven breast cancer presented at National Hospital Organization Nagasaki Medical Center, and 1080 patients were retrospectively analyzed. The favorable (F), intermediate (I), and unfavorable (UF) groups were defined as follows. F: NG1 (ER+PR+, ER+PR-, ER-PR+), UF: NG2 (ER-PR-) or NG3 (ER-PR-, ER+PR-, ER-PR+). IF: all other types of F and UF. Overall survival (OS) was calculated using the Kaplan-Meier method. All statistical analyses were performed using JMP 9.0.2, and probability values of <0.05 were considered statistically significant. Results: Number (%), age (year), size (cm), and 10-year OS (%) in the F, I, and UF groups are presented in the table. The tumor size in F group was significantly smaller than that in the other groups and had better prognoses. The F, I, and UF distribution of tumors less than 1 cm in size were 66%, 29%, and 5%, respectively. On the other hand, the F, I, and UF distribution of tumors 1-2 cm, 2-3 cm, 3-4 cm, 4-5 cm in sizes were (42%, 41%, 17%), (34%, 46%, 20%), (31%, 39%, 30%), and (27%, 45%, 28%), respectively. The 10-year OS of F group stage I, I group stage I, F group stage II, and UF group stage I were 99%, 94%, 93%, and 80%, respectively. Conclusions: Small breast cancers, especially those less than 1 cm in size, were shown to be significantly biologically favorable. Small breast cancers are candidates for de-escalation of treatment. [Table: see text]
A nomogram based on genetic and clinicopathologic features to predict the nonsentinel lymph node metastases in Chinese women breast cancer patients.
Authors: Zhu Liling , Liu Ke , Li Fengyun , Liang Wentao , Shi Wenzhao , Feng Gang , Wang Jiandong 
Published: May 2020

e12577 Background: Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. However, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node (SLN) positive patients. Clinical data reveals 20–60 % of patients without non-sentinel lymph node metastasis (NSLNM) after ALND. Unnecessary ALND increases the risk of lymphedema and detracts from quality of life. In this study, we expect to develop a nomogram based on genetic and clinicopathologic features to predict the risk of NSLN metastasis in SLN-positive Chinese women breast cancer patients. Methods: This retrospective study collected data from 310 women breast cancer patients who underwent SLNB followed by ALND and without any neo-adjuvant therapy in Chinese PLA General Hospital, China, between 2016 and 2017. Genetic features contain 96 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility and prognosis based on the GWAS studies and clinical information. SNP genotyping was identified by the quantitative PCR detection platform. The genetic features were divided into two clusters by the gene functions and signaling pathways. The polygenic risk score (PRS) was used to evaluate the combined effect of each SNP cluster. Least absolute shrinkage and selection operator (LASSO) regression model was adopted for feature selection and nomogram construction. Internal validation was performed and the area under ROC curve (AUC) was assessed. Results: 81 patients of 310 patients (26%) had a positive axillary NSLNM. The LASSO regression analysis identified the clinicopathologic characteristics including molecular subtype, cN-stage, number of positive SLNs and number of negative SLNs as significant predictors of NSLNM. Furthermore, two SNP clusters were also showed statistically significant in the prediction of NSLNM. In internal validation, the average AUC of the nomogram was 0.795 and the model was well calibrated. Conclusions: We present a new nomogram by combining genetic and clinicopathologic factors to achieve higher sensitivity and specificity comparing with traditional clinicopathologic factors to predict NSLNM in Chinese women breast cancer. It is recommended that more validations are required in prospective studies among different patient populations.
Association of Th2 high tumors with aggressive features of breast cancer.
Authors: Tokumaru Yoshihisa , Le Lan , Oshi Masanori , Katsuta Eriko , Matsuhashi Nobuhisa , Futamura Manabu , Yoshida Kazuhiro , Takabe Kazuaki 
Published: May 2020

e12584 Background: Recent studies have shown that infiltrating T-lymphocytes have been implicated in the promotion of breast cancer progression. Upon activation, these antigen-presenting cells then recruit adaptive immune cells. It has been proposed that polarization of CD4+ effector T-cells towards the immunosuppressive Th2 cells induce cytokine release and T-cell anergy, which lead to polarization of M2 tumor-associated macrophages (TAM’s), providing a protumorigenic microenvironment. We hypothesized that there is a correlation between high levels of Th2 cells and aggressive features of breast cancer and unfavorable tumor immune environment. Methods: Clinicopathological data and overall survival information was obtained on 1069 breast cancer patients from The Cancer Genome Atlas (TCGA) database. We defined Th2 high and low levels with the median cutoff. Results: Analysis of cell composition of the immune cells within tumor immune microenvironment demonstrated that Th2 high tumors did not consistently associated with unfavorable tumor immune microenvironment. Pro-cancer immune cells, such as macrophage M2 cells were increased with Th2 high tumors whereas, regulatory T cells were decreased with Th2 high tumors (p < 0.01 and p < 0.001 respectively). On the contrary, infiltration of anti-cancer cells, such as macrophage M1 was increased whereas CD8 T cells were decreased with Th2 high tumors (p < 0.05 and p < 0.001 respectively). Th2 was not shown to have correlation with IL-4, IL-6, IL-10 and IL-13, all of which has been reported to associate with Th2 cells. Th2 levels were associated with advanced grades. Also, correlation analysis demonstrated that there was a strong correlation between Th2 levels and Ki-67. These results were further validated with gene set enrichment analysis (GSEA). GSEA revealed that in Th2 high tumors enriched the gene sets associated with cell proliferation and cell cycle. Conclusions: High expression of immunosuppressive Th2 cells was associated with highly proliferative features of breast cancer, but not with unfavorable tumor immune microenvironment.
Developing a breast cancer tissue biobank in low and middle income countries (LMICs): A research program-based approach for improving molecular profiling.
Authors: Sharma Avinash , Odujoko Oluwole O. , Alatise Olusegun Isaac , Edelweiss Marcia , Ntiamoah Peter , Ogunleye Gbenga Samson , Kingham T. Peter , Iyengar Neil M. ,   African Research Group for Oncology (ARGO)
Published: May 2020

e12585 Background: Breast cancer incidence and mortality is increasing in LMICs especially in sub-Saharan Africa, attributed to changes in lifestyle and possible biological differences. To study putative relationships among lifestyle factors, tumor biology, and the microenvironment, we aimed to develop a breast cancer tissue biobank linked with clinicopathologic and patient reported data in this resource constrained setting. Methods: We prospectively enrolled patients undergoing mastectomy at Obafemi Awolowo University Teaching hospital in Ile-Ife, Nigeria. Pre-operatively, a locally validated survey tool assessed lifestyle factors (diet and exercise); BMI and body composition (by bioimpedence) were measured. Fresh breast tissue was frozen or preserved in 10% neutral buffered formalin, or RNA later for future metabolomic work. Immunohistochemistry (IHC) for ER/PR and HER2 status was performed and read in Nigeria by a locally-trained pathologist, and Memorial Sloan Kettering. The primary outcome was feasibility assessed by successful collection of tissue, clinicopathologic data, and survey completion. Secondary outcomes were completion rate of tumor receptor IHC compared to historic rates and concordance of local vs MSK IHC. Results: From April 2018 to June 2019, 50 patients were enrolled (49 treatment and 1 risk reduction mastectomy). Clinicopathologic, body composition, and survey data, along with breast tissue were collected from all 50 patients. Patient characteristics in table below. Receptor IHC was complete in all patients (100%) compared to a historic rate of 29% (83/286) between 2010-17. Concordance of IHC between sites was 86%, 81% and 84% for subtypes (ER/PR/HER2). Conclusions: Establishing a tissue biobank with clinicopathologic and lifestyle data using locally-adapted protocols is feasible in Nigeria. Patient enrolment is ongoing and updated data will be presented. This initiative also increased local capacity for breast tumor phenotyping, which has critical implications for improving patient care. [Table: see text]