bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of pathological features of estrogen receptor-positive/HER2-negative early breast cancer in the intermediate-risk group of the 21 gene recurrence score (Oncotype Dx) divided into low and high-risk groups by the 95 gene classifier (Curebest 95GC Breast).
Authors: Kamada Yoshihiko , Tsuchiya Seiko , Takigami Naoko , Tamaki Kentaro , Uehara Kanou , Tamaki Nobumitsu 
Published: May 2020

e12535 Background: Oncotype Dx is becoming the standard assay for chemotherapy decision making for estrogen receptor positive / HER2 negative early breast cancer. Issues concerning the choice of therapy for the intermediate risk patients are currently being addressed. We are using a 95-gene classifier developed by Osaka University and Sysmex Corporation (Curebest 95 GC Breast) which divides patients into "low" and "high" risk groups, which obviates this issue. In this study, we analyzed the histopathological characteristics of low and high risk patients by the 95-gene classifier that would be classified as intermediate risk by 21-gene-recurrence score (21RS). Methods: Fresh tissue samples collected at surgery was sent for 95-GC analysis. Cel-files containing the gene expression data of each sample was uploaded to Recurrence Online (recurrenceonline.com) and the 21-RS was obtained. Histopathological analysis of the tumor specimens including the pathological tumor size, degree of tumor infiltrating lymphocytes ("TIL"s) (0, 1+, 2+, 3+), nuclear pleomorphism (NP score 1, 2, 3), and number of mitoses (M score 1, 2, 3) was done. The age of the patient and the Ki-67 percentage of the preoperative biopsy specimen was also noted. Results: There were a total of 38 cases. The cases with a matching 21RS and 95GC "Low" (Group L-L) was 10, a matching "High" (Group H-H) was 15, 21RS "Intermediate / 95GC "Low" (Group I-L) was 4, 21RS "Intermediate / 95GC "High" (Group I-H) was 7, and discordant 21RS "High" / 95GC "Low" (Group H-L) was 2, respectively. There was no age related differences (average 53.3 y.o.). There was a significant difference between the L-L and H-H groups in all categories (i.e. pT 14.5 mm v.s. 30.0 mm / p = 0.0262, NP score average 2.1 v.s. 2.5 / p = 0.287, M score average 1.2 v.s 2.4 / p < 0.001, TILs average 0.4+ v.s. 1.2+ /p = 0.0413, Ki67 25.0% v.s. 33.2%). The trend was the same between the I-L and I-H group with the exception of the mitosis score, which showed an inverse trend of a high of 2.25 in the I-L v.s. low of 1.43 in the I-H group (p = 0.9522). The H-L group had high NP score (average 3.0), low M score (average 1.0), and high TILs (average 2+). Conclusions: The 95-gene classifier might be more sensitive compared to 21RS in picking up histio-morphological information, and also may be able to differentiate the type of immune response of TILs. We are planning further immunohistological evaluation.
Molecular profiling and quantitative image analysis reveal spatial intratumor heterogeneity in TNBC.
Authors: Mittal Karuna , Li Hongxiao , Wylie Dennis , Kaur Jaspreet , Kolachina Rishab , Sahoo Bikram , Wei Guanhao , Toss Michael S , Green Andrew R. , Arasappan Dhivya , Yang Jianchen , Yankeelov Thomas , Bhattarai Shristi , Rakha Emad A. , Gogineni Keerthi , Kong Jun , Kowalski Jeanne , Aneja Ritu 
Published: May 2020

e12536 Background: Triple negative breast cancer (TNBC) is a molecularly complex and heterogeneous subtype with distinct biological features and clinical behavior. Extensive intra-tumor heterogeneity is suspected to be a major cause of therapeutic failure. Spatially-distinct parts of the tumor harbor diverse and divergent clonal populations of cancer cells. Thus it is likely increasing the likelihood that some of those clones resist treatment, expand in numbers and eventually, repopulate the tumor leading to recurrence and spread. Therefore, a deeper understanding of this complexity is fundamental to gaining insights into this clinically important issue. In this study, we used RNA sequencing and machine learning approaches to examine the molecular and phenotypic/cellular profiles of various tumor samples from the same patient tumor to reveal spatial intra-tumor heterogeneity in TNBCs. Methods: We used 34 samples (2-4 samples from each patient tumor) from a total of 11 unique TNBC patients. RNA-sequencing was performed to quantify differential gene expression and machine learning (ML) approaches (deep learning regression modeling) were used to quantify the percentage of tumor and tumor-infiltrating lymphocytes (TILs) in the H&E stained tissue sections. The extent of concordance/discordance between the multiple tumor samples that originated from the same patient was analyzed by analyzing the intra- and inter-patient variance of normalized tumor cell, TIL % and gene expression. We also performed pathway analysis to identify signaling pathways dysregulated within (intra-tumoral heterogeneity) and between tumors (inter-tumoral heterogeneity) and performed molecular subtype analysis. Results: We observed that gene expression variance as higher within-patient (intra-tumor) compared to between-patient (inter-tumor). Tumor samples from 70% of patients showed different molecular subtypes representing extensive intra-tumor heterogeneity. Our ML-based image analysis showed that intra-patient tumor cell and TILs density/percentage variance was greater than inter-patient variance. In addition, patients with high within-patient gene expression variability had a high tumor and TIL variance. Among the within-patient expression variability, the genes associated with the PLK1 and Notch signaling were enriched. Conclusions: Our results suggest that TNBCs exhibit higher intra-tumor gene expression and cellular variance compared to inter-tumor gene expression and cellular variance suggesting higher intra-tumor heterogeneity in TNBCs.
Prevalence of trastuzumab-induced cardiotoxicity in Uruguayan HER2-positive breast cancer patients treated in a real life setting during a 10 year period.
Authors: Camejo Natalia , Castillo Cecilia , Artagaveytia Nora , Etcheverría Crisitian , Ferradaz Jessica , Ferreira Agustín , Fontán Analía , Gabín Ana Sofía , Delgado Lucia Beatriz 
Published: May 2020

e12537 Background: To estimate the prevalence of Trastuzumab (TTZ) induced cardiotoxicity in Uruguayan women diagnosed with early HER – 2 positive breast cancer (BC) over a period of ten years, treated under the financial coverage of the National Resource Fund (FNR). Methods: A prospective descriptive observational study based on the analysis of an anonymized database provided by the FNR of Uruguayan HER-2 positive early BC patients treated with TTZ between 2006 and 2016. Variables analyzed included: age, menopausal status, stage, presence of cardiovascular risk factors, use or not of anthracyclines, left ventricular ejection fraction prior and during treatment, and temporary or permanent suspension of treatment. Statistical analysis was performed using SPSS Statistics version 25. The variables were assessed through the use of measures of central tendency, dispersion, contingency tables and proportions. To analyze the relationship between the different variables, the Chi-Square test of independence was performed. Results: The analysis included 1401 patients diagnosed with HER-2 + stage I to III breast cancer who received adjuvant TTZ. The mean age at diagnosis was 52.45 years. The prevalence of cardiotoxicity in evaluable patients (1065 pts) was 20.3%. The proportion of patients who had symptomatic heart failure was 3% (32 pts) and in those who discontinued treatment for asymptomatic cardiac toxicity managed to resume trastuzumab prevalence was 92.6 %. About 9,7 % (21 pts) of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% drop of LVEF below their baseline levels were found in 75% of patients (162 pts) There is significant difference in the risk of cardiotoxicity according to the type of chemotherapy (anthracycline containing vs non-anthracycline based) (Chi-square = 3.9, p-value < 0.005). There was no evidence of a relationship between cardiovascular risk factors and the development of cardiotoxicity as well there was no evidence between sequential or concurrent use of TTZ with chemotherapy. Conclusions: The prevalence of cardiotoxicity in this study was similar to that reported internationally. The majority of patients did not develop cardiac toxicity and those who presented it did so asymptomatically and reversibly.
Correlation between five-year overall survival by PREDICT and 21 gene recurrence score (RS) in a Mexican private institution.
Authors: Amador García Geovani , Serrano Villamayor Omar , Andrade Moreno Raul Alejandro , Rodríguez Meléndez Elina Alexandra , Martínez-Herrera José Fabián , Sánchez Rodríguez Alain , Reyes Eduardo , Olivares Guillermo , Villalobos Alberto , Aguayo Alvaro , Perez-Zincer Fernando , Camacho Limas Christian Patricio , Lazaro Jesus Miguel , Serrano Juan Alberto , Gerson Cwilich Raquel 
Published: May 2020

e12543 Background: In México the 5-year overall survival of Early Breast Cancer (EBC) reaches to 82-97%. Oncotype Dx evaluates the expression of 21 genes associated with recurrence and classifies patients into risk groups. PREDICT (https://breast.predict.nhs.uk/tool) is an online tool which assesses 5 and 10 year overall survival in breast cancer patients who receive adjuvant chemotherapy, adjuvant hormonal therapy and trastuzumab therapy for HER2(+) patients. Methods: Retrospective review of medical records of early stage breast cancer patients with (HR+) and HER2 (-) treated at our institution. Clinicopathological characteristics and (RS) were collected. 5-year overall survival was calculated with the PREDICT online tool. Both scores were compared and the correlation was estimated with Spearman’s Rho and global agreement with intraclass correlation coefficient (CCI), statistical software: STATA SE ver11.0 (StataCorp LLC Texas,USA). Results: From January 2008 to December 2018, 136 patients with EBC (IA-IIB), HR(+) HER2(-), N0-1 were included. The Median age at diagnosis was 55.03 years (30-80). Stage IA patients accounted for 68.38% of the population. Patients were classified into risks according to the original description of Oncotype. 72 patients (53%) were classified as low risk (LR), 49 (36%) at intermediate risk (IR) and 15 (11%) patients at high risk (HR). When reclassifying the risk categories using the cut-off values in TAILORx trial, the population distribution was modified, with a notable increase in the population in IR with 86 (63.2%) patients in this group, 28 patients in the LR group ( 20.5%) and 22 patients (16.1%) in HR. We decided to use TAILORx cut-off values for the aim of this work. Mean overall survival established by the 21 gene RS was 98% for the overall population. The mean overall survival calculated by PREDICT was 93%. Spearman’s correlation coefficient was 0.16 (Spearman’s Rho = 0.16 p = 0.065) with intraclass correlation coefficient (ICC) = 0.04 (IC 95% -0.15 – 0.22, p = 0.33). Conclusions: The results do not show a clear correlation between the tests. Lack of such correlation may be due to a low number of patients. In our population PREDICT couldn't replace the RS test for therapeutic decision making.
Real-world data on adjuvant bisphosphonate use in a breast cancer center in Mexico.
Authors: Peña-Curiel Omar , Villarreal-Garza Cynthia , Díaz-Pérez Héctor , Martinez Trevino Enrique Francisco 
Published: May 2020

e12544 Background: Results from the Early Breast Cancer Trials Collaborative Group (EBCTCG) meta-analysis published in 2015 showed a significant reduction in risk of distant recurrence, bone recurrence and a 10-year breast cancer mortality reduction1. Moreover, Cancer Care Ontario and ASCO issued a guideline regarding the use of adjuvant bisphosphonates (AB) in breast cancer postmenopausal patients2. While these data are compelling, we have no information to support the implementation of this recommendation at Hospital San José’s Breast Cancer Center (HSJBCC). Methods: A retrospective analysis was performed to evaluate our compliance to the current recommendations for AB administration from 2015 through 2019. Inclusion criteria were based on the ASCO guidelines and comprised invasive breast cancer, postmenopausal status and early or locally advanced stage. Furthermore, in AB-treated patients we assessed the percentage of baseline calcium and creatinine measurement, prior dental evaluation, and concurrent calcium and vitamin-D supplementation during AB use. Results: A total of 106 patients met the inclusion criteria. Within the 4-year timeframe, AB was prescribed to 28/106 (26%) patients. Stratifying by year, we observed an increase of AB use rate from 4% in 2015 to 32% in 2019. Moreover, we observed a 93% baseline calcium and creatinine measurement, a 60% prior dental evaluation, and a 43% concurrent calcium and vitamin-D supplementation in the AB-treated population. Conclusions: HSJBCC recommendation for AB use is less than expected in the evaluated eligible patients in the 4-year timeframe. Despite an increase in our compliance to current ASCO guidelines it is not yet the standard of care at HSJBCC. Based on these results, we are currently planning a quality improvement initiative to undertake our low percentage of AB usage. [Table: see text]
Depression in women breast cancer patients receiving radiation therapy: A pilot study.
Authors: Chen Fang , Yu Hao , Zhao Caining , Zhang Fan , Nong Yaqing , Xu Zhiyuan , Yang Li , Chen Wenqi , Wang Qian , Zhou Yong , Han Yin , Jing Haiman , Kong Feng-Ming 
Published: May 2020

e12546 Background: The purpose of this study is to study depression and its risk factors at baseline and explore the changes of depression status during the course of radiation therapy in breast patients. Methods: This is part of a prospective study of treatment toxicity and quality of life. Breast cancer patients, aged 18-year old and above requiring adjuvant radiation therapy were eligible. The primary endpoint depression was assessed by a self-addressed “depression” questionnaires according to NCI “PROMIS”. The Questionnaires were completed one day prior to, during and at the end of treatment. Patient, tumor and prior treatment factors were collected. Cancer specific symptoms were collected by treating physicians and graded according to NIH/NCI CTCAE v4.0. The variables of our interest included age, menopausal status, N-stage,pathology stage, immunohistochemisty, surgical approaches,margin,prior treatments and radiation models. Data are presented as mean (95% confidence interval) unless otherwise specified. Statistical significances were tested using generalized linear model, pearson correlation and t-text. Ps less than 0.05 were considered to be significant. Results: Between July 2019 and January 2020, a total of 185 patients enrolled and completed the PROMIS questionaires. Before RT commencement, 50/185 (27.0%) had some levels of depressive feeling including 40/185 (21.6%), 10/185 (5.4%), and 0/185 (0%) patients for “rarely” (score = 5-8), “sometimes” (score = 9-12), “often” (score = 13-16), and “always” (score 17-20), respectively. Interestingly, N stage and pathology staging group were significantly associated with the depression at baseline while age, menopausal status, immunohistochemistry, previous chemo cycles, chemo regimens and anti-Her2 taget therapy were not. At the end of RT, 51/149 (34.2%) patients had depression level changed, though the absolute lumped scores of depression did not change significantly (p = 0.437). Changes in depression during were significantly associated with menopausal status (p = 0.015) while grade 2 and above toxicities were not (p = 0.421). Conclusions: Depression feeling is not uncommon in breast patients receiving adjuvant radiation. Future study may identify patients with depression and associated risk factors so that proper intervention may be applied to improve long-term survival and quality of life in patients.
Survival outcomes in post-menopausal patients with underlying cardiovascular disease receiving endocrine therapy for the treatment of breast cancer.
Authors: Parajuli Priyanka , Lara Garcia Odalys Estefania , Maini Ruby , Regmi Manjari Rani , Tandan Nitin , Mirihagalle Noupama , Cheema Asad , Abedrabo Sabree , Niaz Zurain , Koester Cameron , Sahib Hamsa , Bhandari Bishal , Johnson Alexander , Ibrahim Abdisamad M. , Delfino Kristin , Robinson Kathy , Desai Meghna R. , Kulkarni Abhishek 
Published: May 2020

e12549 Background: Breast cancer remains the number one threat to women’s health while cardiovascular disease (CVD) continues to be the leading cause of mortality in women worldwide. Adjuvant therapy with endocrine therapies (selective estrogen receptor modulators (SERM), estrogen receptor blockers (ERB), and aromatase inhibitors (AI) although known to reduce the recurrence of breast cancer in hormone receptor positive breast cancer patients, raise a concern for increased risk of cardiovascular disease. Our study aims to examine breast cancer survival outcomes on patients receiving endocrine therapy who have pre-existing CVD including heart failure. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Preexisting CVD included coronary artery disease (CAD), history of myocardial infarction (MI), and prior diagnosis of heart failure (HF). Patients were divided in groups depending on treatment with endocrine therapy and underlying CVD. Statistical analysis was performed with SAS v9.4. software. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance was assumed at the p < 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Out of those 336 patients, 62.2 % (n = 209) received at least one of the endocrine therapies consisting of AI, SERM or an ERB. Of these patients, 2.9 % (n = 6), 9.6% (n = 20) and 5.7% (n = 12) had a significant medical history of underlying MI, HF and CAD, respectively. Survival analysis was performed on 80% (n = 168) patients of the 209 patients with 2.3% (n = 4), 8.9% (n = 15) and 5.2% (n = 11) with underlying MI, HF and CAD respectively. There was no statistically significant difference in survival in these postmenopausal women who received endocrine therapy despite preexisting cardiovascular disease (HR 3; 95% CI, 0.5-16, p > 0.05). Conclusions: A commonly known toxicity related to the adjuvant therapy including endocrine therapy of breast cancer is cardiac toxicity. Patients with history of CVD might be at the highest risk for such toxicity. Our finding is reassuring that endocrine therapy in patients with preexisting CVD including heart failure did not result in reduced survival for our patient cohort.
ER-/PgR+ breast cancer is a separate entity characterized by distinct phenotype: Comprehensive reevaluation of cases from Polish and Hungarian centers.
Authors: Senkus-Konefka Elzbieta , Kunc Michał , Pęksa Rafał , Łacko Aleksandra , Radecka Barbara , Braun Marcin , Pikiel Joanna , Litwiniuk Maria , Pogoda Katarzyna , Cserni Gabor , Iżycka-Świeszewska Ewa , Szwajkosz Anna , Biernat Wojciech 
Published: May 2020

e12554 Background: ER negative (-)/PgR positive (+) breast cancer (BC) is very uncommon and questioned by many experts. We comprehensively reevaluated ER-/PgR+ BCs in the large cohort from Polish and Hungarian centers. Methods: FFPE blocks from 105 ER-/PgR+ tumors (45 breast biopsies and 64 post-operative samples from tumors not exposed to systemic therapy) were collected from 10 Polish and 3 Hungarian centers. In 60 cases available original slides with ER/PgR staining underwent reevaluation by 3 pathologists (MK, RP, WB) for ER and PgR expression by ASCO/CAP criteria. Subsequently, all samples were stained with 3 antibodies against ER (Dako monoclonal (MC) mouse anti-ERα, clone 1D5; Dako MC rabbit anti-ERα, clone EP1; VENTANA Roche MC rabbit anti-ERα, clone SP1), and PgR (Dako MC mouse anti-PgR, clone 636). If available, > 1 tissue block was used (av. 2.04 blocks/case, range 1-6). In 5 cases ESR1/PGR/ERBB2/MKi67 mRNA was measured by the Xpert® Breast Cancer STRAT4 (Cepheid, Sunnyvale, CA, USA). Results: 13 cases were excluded from immunohistochemical steps of the study due to insufficient amount of tissue and 8 - due to misdiagnosis after ER/PgR reevaluation of original slides. After re-staining, 42 cases (41.5%) retained the original phenotype, in 34 (33.67%) the ER status was corrected to ER+, and 16 (15.84%) tumors were ER/PgR-double-negative. The general agreement between anti-ER clones was moderate (Fleiss’ κ = 0.54). There were 56 ER- and 16 ER+ cases across all three assays. Five cases showed ER positivity with 2 antibodies (either SP1/EP1 or SP1/1D5), 5 tumors reacted exclusively with SP1 clone, and 2 - with 1D5 clone. Xpert Breast Cancer STRAT4 confirmed the ER-/PgR+ phenotype in 4 of 5 analyzed cases. The confirmed ER-/PgR+ BCs were characterized by lower percentage of PgR+ cells (median 5%) than BCs reclassified to ER+ (median 70%) (p = 0.022) and higher Ki67 expression than ER+ cases (median 54.5% vs 25%, respectively; p = 0.003). 39 (92.85%) ER-/PgR+ BCs presented with grade 3. Besides “conventional” high-grade cancers, we identified two distinct morphologies of ER-/PgR+ BC: resembling apocrine carcinoma (n = 5, 11.9%) and carcinoma with central acellular zone (n = 4, 9.5%). Conclusions: ER-/PgR+ BCs confirmed in the current study were defined by high-grade histology, high proliferation index and low percentage of PgR+ cells. We postulate ER-/PgR+ BC is a real albeit rare entity, and its diagnosis should be made cautiously, utilizing retesting with an alternative tissue block and anti-ER antibody.
Significance of PDL1 positive in TNBC.
Authors: Imanishi Seiichi , Morishima Hirotaka , Oda Naofumi , Hasegawa Junichi 
Published: May 2020

e12557 Background: Atezolizumab was approved for PD-L1-positive advanced recurrent triple negative breast cancer. However, it is controversial about when and when to measure PD-L1. Here we retrospectively reaearched how PD-L1 positivity rates in biopsy, surgical, and recurrent specimens for triple-negative breast cancer (TNBC) treated with neo adjuvant chemotherapy (NAC). We also investigated the relationship between androgen receptor (AR) and PD-L1, and researched the significance of PD-L1 positivity on TNBC. Methods: 28 TNBC biopsy samples before NAC, 16 surgical specimens with residual tumor after NAC, and 5 cases reccurence specimens were obtained subjected to stain for PDL1 using the SP142 antibody. AR staining was also performed on biopsy specimens. PD-L1 score determination was performed according to the Ventana OptiView PD-L1 (SP142) inspection guide, and AR positive cuttoff was setted 1% or more. Results: The PD-L1 positivity rates of the biopsy samples were IC0: 46.4%, IC1: 25.0%, IC2: 21.4%, IC3: 7.1%, TC0: 28.6%, TC1: 28.6%, TC2: 42.9%, TC: 0%. In the surgical specimens after NAC, PD-L1 showed almost no change in IC ( P = 0.38), but the score significantly decreased in TC ( P < 0.001). The recurrence specimesn that could be collected were IC0: 60%, IC1: 20%, IC2: 20%, IC3: 0%, TC0: 60%, TC1: 20%, TC2: 20%. There were four AR-positive cases, one of which showed TC2, but the others were negative.In terms of prognosis, both the DFS and OS in the PD-L1 strongly positive group (IC≥2 and TC≥2) and other groups Poor in PD-L1 strongly positive group ( P < 0.01, P = 0.041, respectively). Conclusions: TC was affected by NAC, the score decreased markedly, and the positive rate at the site of recurrence also tended to decrease. The PD-L1 strong positive had a significantly worse prognosis than the others. It was suggested that PD-L1 immunostaining may be effective in predicting prognosis by considering TC as well as IC.