bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS18-45: Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer
Authors: Philipovskiy Alexander , Dwivedi Alok , Gamez Roberto , McCallum Richard , Nahleh Zeina , Aguilera Renato , Gaur Sumit 
Published: February 2021

Abstract
Triple-negative breast cancer (TNBC) represents approximately 15-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women and has more aggressive course. The biology of TNBC in HL women has been poorly characterized, but some data suggest that molecular drivers of breast cancer might be different. Chemotherapy remains the only option for those patients. There is no clinical tool to help medical oncologist with the decision about appropriate individual chemotherapy, as well as no way to predict long-term outcomes. The aim of the study was to characterize individual patient gene expression profiles and to identify the relationship with clinical outcomes.Patients and Methods: From 2012-2019, we collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. All specimens were carefully examined by pathologists for adequacy and for a hormonal status. We analyzed gene mutation profiles of collected tumors and associated results with individual patient’s clinical history and outcomes.Results: Of 25 patients with TNBC, 24 (96%) identified as HL, one patient as NHL. Twenty-one (84%) had stage III/IV disease, and four (16%) had stage II at the diagnosis. Most commonly mutated genes were: TP53, Notch, AKT, MEP3K, PIK3CA and EGFR. Compared to other international cancer databases mostly included NHW, AA and Asian women, our study demonstrated statistically significant higher frequencies of those among HL women. With TNBC. Also a worse clinical course was among those patients whose tumor had mutations in Notch and PIK3CA. Conclusion: In conclusion, this study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could be different in HL women. Therefore, a deeper understanding of the biological mechanisms behind Notch, PIK3CA mutation, might lead to a new treatment approach.
Citation Format: Alexander Philipovskiy, Alok Dwivedi, Roberto Gamez, Richard McCallum, Zeina Nahleh, Renato Aguilera, Sumit Gaur. Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-45.
Abstract PS18-48: Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue
Authors: Sutherland Rachel Jane , Meeson Annette , Lowes Simon 
Published: February 2021

Abstract
Essential nutrient uptake required for cell growth and survival is mediated by Solute Carrier (SLC) transporters both physiologically and in cancers. The SLC super-family encompasses sub-families of transport proteins including organic anion transporters (OAT), organic cation transporters (OCT) and organic anion transporting polypeptides (OATP). SLCs transport a vast array of endogenous and exogenous substances, including estrogen, its conjugates, and clinically relevant anti-cancer drugs. Accumulating evidence suggests that SLC transporters are differentially expressed in hormone-responsive and hormone non-responsive breast cancers, which could influence breast cancer pathogenesis, both in disease progression and treatment resistance. We investigated whether SLC transporters are differentially expressed in different breast cancer cell lines and in human breast cancer tissue. First, bulk cells from the breast cancer cell lines MCF-7 (hormone responsive) and MDA-MB-231 (hormone non-responsive) were analysed for differential expression of SLCs using sq-PCR and RT-PCR. 8 of 11 SLCO and 10 of 14 SLC22 transporters were expressed in at least one cell line. Transporter expression was either similar or lower in MCF-7 cells compared to MDA-MB-231 cells, with the exception of SLCO2A1, SLCO4C1, SLCO5A1 and SLC22A5 which were higher in MCF-7 cells. mRNA expression of SLCs was then compared between both cell lines and human breast cancer tissue. The latter showed an expression pattern largely reminiscent of the MCF-7 cells. Because these techniques measure the average level of expression shown by a pooled cell population, there is the potential disadvantage that cell heterogeneity is masked. To help address this, Single Cell RNA Sequencing (scRNA-Seq) was performed using the 10x Genomics Chromium Single Cell 3’ platform and NovaSeq Technologies to compare SLC transporter expression between the cell lines. Together these results provide evidence for differences in SLC transporter expression between cell lines and cancer tissues that may contribute to cancer progression.
Citation Format: Rachel Jane Sutherland, Annette Meeson, Simon Lowes. Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-48.
Abstract PS18-51: Leptin receptor expression in breast tumors and chromatin modulators: A comparative study
Authors: Pacheco Sara , Juarez Maria E. , Nandy Sushmita 
Published: February 2021

Abstract
Metabolic dysregulation and carcinogenesis are strongly linked. Leptin signaling acts as a metabolic switch that maintains body weight and energy homeostasis and gets impacted during metabolic dysregulation. Leptin signaling mediates its effect on breast cancer cells through downstream effectors like JAK-STAT, MAPK and PI3K pathways. At the molecular level, leptin exerts its effects through its receptor, LEPR, encoded by LEPR gene. Leptin signaling has been shown to contribute towards progression of breast cancer. Obese post-menopausal women are considered to be a high-risk category for breast cancer and dysregulated leptin signaling contributes towards it. We in this study focused on comparative molecular analysis of Leptin high (LEPRhi) and low (LEPRlow) expressing breast tumors.Breast cancer data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study was used through the cBioPortal (http://cbioportal.org) platform for cancer genomics. The METABRIC study includes clinical and molecular data from over 2500 breast cancer cases. The LEPRhi and LEPRlow expressing breast tumors in RNA-seq dataset were queried using cBioPortal embedded SQL feature as LEPR: EXP&gt;1 and LEPR: EXP&lt;-1 respectively. This query enabled us to create LEPRhi and LEPRlow expressing breast tumor cohorts from 243 and 234 patients respectively. Comparative analysis of LEPRhi and LEPRlow expressing breast tumors was performed for mRNA expression profiles. The mRNA data was further analyzed for integrated networks using GSEA pathway enrichment and CR2-cancer algorithms.The analysis indicated unique mRNA expression signature for LEPRhi and LEPRlow breast tumors. CR2-Cancer analysis of the mRNA dataset revealed chromatin modulators like- EZH2 (Enhancer of Zeste homolog 2), MEN1 (Menin), UHRF1 (Ubiquitin Like with PHD And Ring Finger Domains 1), TTF2 (Transcription termination factor 2), LMNB2 (Lamin B2), and RUVBL2 (RuvB Like AAA ATPase 2) had significantly higher mRNA expression in LEPRlow compared to LEPRhi tumor group. GSEA pathway enrichment analysis indicated PLK1 and Aurora A signaling as the most significant signaling pathways with an FDR q-value of less than 0.05.This preliminary study provides us with mechanistic insight into the unique molecular signatures of LEPRhi and LEPRlow expressing breast tumors. The results of this study leads to the basis of our hypothesis that leptin receptor signaling in breast cancer mediates epigenetic modifications of key genes that impact promotion and progression of breast cancer through chromatin modulators.
Citation Format: Sara Pacheco, Maria E. Juarez, Sushmita Nandy. Leptin receptor expression in breast tumors and chromatin modulators: A comparative study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-51.
Abstract PS19-13: Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts
Authors: Harlow Brittany Susanne , Davalos Albert , Brenner Andrew , Jolly Christopher , Tiziani Stefano , Hursting Steve , deGraffenried Linda 
Published: February 2021

Abstract
Background: Obesity is associated with a worse breast cancer prognosis, conferring an increased risk of recurrence and mortality. At the same time, recent evidence suggests that obesity is also correlated with development of cellular senescence, an inflammatory state associated with exacerbation of breast tumorigenesis in preclinical models. As obese individuals present greater levels of inflammation at baseline, research efforts are warranted to examine the means by which obesity promotes the development of a senescent phenotype, which may further exacerbate inflammation. Additionally, studies have yet to determine whether obesity-induced senescence modulates the tumorigenic process in the context of breast cancer specifically. Methods: To this end, we exposed fibroblasts to the obesity-associated circulating factor palmitate and used qPCR and western immunoblotting to assess the expression of genes and proteins involved in the senescent state, including interleukin (IL)-1a, IL-6, IL-8, senescence-associated beta-galactosidase (SA-beta-gal), and matrixmetalloproteinase (MMP)-9. As a mechanistic investigation, we next assessed the impact of palmitate on activation of NF-kB signaling using western immunoblotting, immunofluorescence, and NF-kB luciferase reporter assays. Finally, we utilized cell counting, MTT, wound healing, and colony formation assays to examine the impact of these palmitate-exposed fibroblasts on breast cancer cell proliferation, viability, motility, and survival, respectively. Results: We found that palmitate induced fibroblast gene expression of IL-1a, IL-6, and IL-8, major components of the senescent secretome, as well as expression of the senescent markers SA-beta-gal and MMP-9. The mechanism at least partially involved activation of NF-kB, responsible for production of about 75% of senescent secretome components. More importantly, these palmitate-exposed fibroblasts were of pathological impact, exacerbating in vitro measures of breast cancer cell aggressiveness. Conclusions: These findings contribute to our understanding of the impact of obesity-associated factors on breast tumorigenesis, demonstrating a mechanistic link between palmitate and the pro-tumorigenic effects of senescent cells. Our studies will ultimately aid in the identification of a therapeutic target that can be used to improve the comparably worse outcomes of the obese breast cancer patient.
Citation Format: Brittany Susanne Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stefano Tiziani, Steve Hursting, Linda deGraffenried. Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-13.
Abstract PS19-23: Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer
Authors: Amioka Ai , Kadoya Takayuki , Sueoka Satoshi , Kobayashi Yoshie , Sasada Shinsuke , Emi Akiko , Masumoto Norio , Ito Masaoki , Okada Morihito 
Published: February 2021

Abstract
Purpose: We previously showed that Wnt5a-positive breast cancer belongs to a subgroup of estrogen receptor (ER)-positive breast cancers and its prognosis is worse than that of Wnt5a-negative breast cancer. In this study, we aimed to investigate the molecular mechanisms underlying the poor prognosis of patients with Wnt5a-positive breast cancer.Methods: A total of 151 patients with ER-positive invasive breast cancer were recruited for this study between January 2011 and February 2014. The association between Wnt5a expression and recurrence rate was examined. To identify the pathways associated with Wnt5a-positive breast cancer, we established a Wnt5a-expressing cell line (MCF-7/Wnt5a cells) and conducted DNA microarray analysis of MCF-7/Wnt5a cells. We also performed pathway analysis associated with Wnt5a expression, and evaluated the effects of Wnt5a in vitro using MCF-7/Wnt5a cells.Results: Data showed poorer relapse-free survival of patients with Wnt5a-positive breast cancer (P = 0.047). The median length of follow-up was 6.08 years (range, 0.027 to 8.47 years) for all patients. According to DNA microarray data, only the cytochrome P450 (CYP) pathway was significantly upregulated and related with Wnt5a (P = 0.0440). Moreover, MCF-7/Wnt5a cells were less sensitive to tamoxifen and paclitaxel, which are metabolic substrates of CYP (P &lt; 0.05). Although the PI3K-AKT-mTOR signaling pathway is involved in the poor prognosis of ER-positive breast cancer, it was not associated with Wnt5a.Conclusions: In ER-positive breast cancer, Wnt5a expression upregulated the CYP metabolic pathway and decreased the sensitivity to tamoxifen and paclitaxel, the standard treatment options for ER-positive breast cancer.
Citation Format: Ai Amioka, Takayuki Kadoya, Satoshi Sueoka, Yoshie Kobayashi, Shinsuke Sasada, Akiko Emi, Norio Masumoto, Masaoki Ito, Morihito Okada. Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-23.
Abstract PS2-22: The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections
Authors: Lundgren Claudia , Sjöberg Fanny , Olofsson Helena , Lindman Henrik 
Published: February 2021

Abstract
Background: Several studies have reported good or reasonable concordance of biomarker panel based on core needle biopsies (CNB) and the pathology based on the surgical specimen (SS). However, as neoadjuvant therapy (NAC) is becoming more common, the result from the preoperative CNB is crucial as it is the only source for the subtyping of the breast tumor. Incorrect results of subtype could result in suboptimal choice of NAC. The aim of this study was to estimate the sensitivity and specificity of biomarkers and surrogate subtypes based on CNB compared with the surgical specimen (SS) in a three-year cohort of primary breast cancer patients diagnosed at Uppsala University Hospital.
Patients and Methods: We collected data from all patients diagnosed with breast cancer at the University Hospital Uppsala, between 1st of September 2015 and 31st of August 2018 (n=837). Of these, 319 primary operated tumors were available with full biomarker information on CNB and SS. An additional 71 tumors from patients treated with NAC could be identified (not reported). Histopathological results from CNB and SS (n= 319) were used to divide the tumors in five subtypes; luminal A, luminal B, triple negative (TNBC), HER2-luminal and HER2 non-luminal.
Results: The sensitivity/specificity of CNB for the expression of estrogen receptor was 100%/100%, progesterone receptor 96%/77%, HER2 by IHC3+ 77%/99%, Grade 3 49%/89% and high Ki67 72%/78%. The sensitivity and specificity of CNB and SS in subtype TNBC and HER2 non-luminal subtypes was 100%. Out of 37 cases with HER2-luminal subtype, 27 were correctly diagnosed by CNB (sensitivity 73%, specificity 100%). The sensitivity for correct diagnosis of luminal A was 76% with a specificity of 83% and luminal B subtype had a sensitivity of 74% and 99% specificity.
Conclusions CNB was very reliable in defining TNBC and HER2 non-luminal subtypes, but less accurate in diagnosing luminal subtypes. There is a clear risk for underdiagnosis of HER2-luminal tumors. These patients might therefore receive suboptimal treatment when treated with NAC.
Citation Format: Claudia Lundgren, Fanny Sjöberg, Helena Olofsson, Henrik Lindman. The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-22.
Abstract PS3-24: Using big data to gauge effectiveness of breast cancer awareness month
Authors: Gathers Diamone A. , Pankratz Vernon S. , Tawfik Bernard 
Published: February 2021

Abstract
Introduction: Breast Cancer Awareness Month (BCAM) has been used for decades to increase awareness and screening for breast cancer but it’s reach and effectiveness is difficult to judge. Using Internet Search Interest (ISI) could allow better evaluation of BCAM effects.Methods: Using Google Trends, we evaluated the ISI of a given term(s) as compared to that cancer’s awareness month. The ISI represents population level Google internet searches relative to the highest number of searches for the United States from 2004-2019 with a max number of 100. The ISI for breast cancer and mammogram in October, which is BCAM, was compared against all other months during this period. Results: The BCAM of October was associated with statistically significant more ISI for breast cancer 77.0 vs. 34.6 (95% CI 69.5-84.5, CI 32.9-35.3, p &lt; 0.0005) as compared to the rest of the year. ISI for mammogram was similar (41.6 vs. 60.2, 95% CI 39.4-43.7, 48.5-71.9, p = 0.007). There was significant differences between the top half of states with Mississippi (100), Delaware (97) and West Virginia (95) having the highest ISI while Nevada (60), Oregon (60) and Utah (57) the lowest (87.6 vs 71.8, 95% CI, 85.5-89.7, 69.0-74.6, p &lt; 0.0005). There was significant differences between the top half of 208 United States metro areas with Rochester MN (100), Greenwood MS (85) and Jackson MS (80) having the highest ISI while Salt Lake City UT (43), Idaho Falls UT (41) and Roanoke VA (40) the lowest (67.5 vs 54.4, 95% CI, 66.4-68.6, 53.4-55.4, p &lt; 0.0005). Conclusion: ISI suggests that BCAM is effective at increasing breast cancer awareness with significant heterogeneity across states and metro areas. This publicly available free tool can be used to assess penetrance of awareness campaigns in a time sensitive manor for future targeting of populations with low breast cancer awareness. Future research is needed to correlate outcomes and ISI.
Citation Format: Diamone A. Gathers, Vernon S. Pankratz, Bernard Tawfik. Using big data to gauge effectiveness of breast cancer awareness month [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-24.
Abstract PS3-27: 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response
Authors: Guarin Marco , Azar M. Eugenia , Tinetti Carolina , Mansilla F. M. Dolores , Namias Mauro , Carballo Pilar , Santamarina Lucia , Cavallero Jorgelina , Moreau Romina , Gonzalez Christian , Caceres Valeria , Gonzalez Eduardo , Bruno Gabriel 
Published: February 2021

Abstract
Introduction: Residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC) can accurately predict disease recurrence and survival in breast cancer. In this context, end of treatment (EOT) image-guided response assessment could be useful to adapt treatment for individual patients. Our main objective was to assess the effectiveness of 18F-FDG PET/CT and MRI in determining NAC response. Methods: Patients with surgically resectable breast cancer (stages II-III) were prospectively included and evaluated with 18F-FDG-PET/CT and MRI before and after standard-of-care neoadjuvant chemotherapy (NAC). Ultrasound guided breast biopsy was performed before NAC and pathologic examination with residual cancer burden (RCB) scoring was performed after surgery. Standard uptake values (SUVmax and SUVmean) from baseline PET scans were measured. EOT images results were compared with RCB scores to assess the sensitivity and specificity of (EOT) 18F-FDG-PET/CT and MRI images. A multinomial logistic regression was performed to assess predictors of pathological response. A p-value of 0.05 was considered significant. Results: 30 patients were included, with 25% showing complete pathological response. EOT 18F-FDG-PET/CT images had a sensitivity of 55% and specificity of 100% to predict RCB &gt; 0, while EOT MRI had a sensitivity of 65% and specificity of 66,6%. Luminal tumors showed significant lower baseline SUVmean and SUVmax values than triple-negative tumors. Ki67 expression didn´t correlate with treatment outcome. High estrogen receptor expression level was significantly associated with non-complete pathological response and higher false negative rates in both EOT 18F-FDG-PET and MRI images (7/8 in PET and 6/7 in MRI). Conclusions: 18F-FDG-PET / CT could be a useful diagnostic tool to assess neoadjuvant chemotherapy treatment response in breast cancer, showing greater specificity than MRI to predict pathological response. A high expression of estrogen receptors could lead to a high rate of false negative findings, both in PET and MRI. A greater number of cases is required to validate these findings.
Citation Format: Marco Guarin, M. Eugenia Azar, Carolina Tinetti, M. Dolores Mansilla F., Mauro Namias, Pilar Carballo, Lucia Santamarina, Jorgelina Cavallero, Romina Moreau, Christian Gonzalez, Valeria Caceres, Eduardo Gonzalez, Gabriel Bruno. 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-27.