bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-03-04: Stereotactic vaccum-assisted breast biopsy: A cost effective diagnostic method for suspicious calcifications investigation in Brazil
Authors: Amorim Andressa , Ramos Marcellus N. M. , Sawada Maria Isabela B. A. C. , Mattar André , Shida Jorge Y. , Gebrim Luiz H. 
Published: March 2020

Abstract
Background: Mammographic screening carried out in Brazil's Public Health System (SUS) is opportunistic and restricted to large cities mainly in the South and Southeast regions. However, only 30% of the suspicious calcifications are confirmed to be malignancy after the biopsy. The surgical procedure to investigate is still the routine in most centers in Brazil. A vacuum assisted stereotactic biopsy (VASB) is expensive and it is not available in most centers in the developing countries. Objective: To estimate saved values in SUS by performing VASB instead of performing classic surgical procedure in the investigation of suspicious calcifications. Methods: We’ve performed a retrospective and descriptive study from July, 2012 to June, 2019, in which 1,809 patients diagnosed with suspicious calcifications on mammography (BIRADS 4 and 5) had VASB performed at Hospital Estadual Pérola Byington. The device used was Surus Pearl (Hologic, Malbolrough, Massachusetts, USA) with probe gauge 9. The biopsy`s costs were calculated and estimated in terms of American Dollars (US$) in 2019. No direct medical and nonmedical or indirect costs have been evaluated. Results: the histopathological study of the lesions revealed benign alterations in 1,179 (65.1%) The findings were positive for malignancy in 533 (29.5%) and the precursor lesions were diagnosed in 97 (5.4%) VASB is an outpatient procedure; a single biopsy has an average cost of US$ 36. Instead, the classic surgical procedure is a procedure that requires hospitalization and general anesthesia with estimated cost of US$ 97 for every single procedure. The saved values in that time by SUS were US$ 29,077. Conclusion: we found a high economic impact of VASB in the SUS scenario. Lower costs than surgical procedures and being an outpatient procedure may indirectly increase hospital beds` supply for cancer treatment. Studies focusing on other direct and indirect costs are desirable, especially in developing countries.
Keywords: calcifications; vacuum-assisted stereotactic biopsy; breast cancer.
Citation Format: Andressa Amorim, Marcellus N. M. Ramos, Maria Isabela B. A. C. Sawada, André Mattar, Jorge Y. Shida, Luiz H. Gebrim. Stereotactic vaccum-assisted breast biopsy: A cost effective diagnostic method for suspicious calcifications investigation in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-03-04.
Abstract P4-04-09: The acquired resistance of mammary cancer cells to CDK4/6 inhibitors drives a DNA methylation reprogramming of genes encoding for BCL2 family members that confers a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug
Authors: FRENEL Jean-Sebastien , Voisin Deborah , Nadaradjane Arulraj , Bougras-Catron Gwenola , Campone Mario , Serandour Aurelien , Cartron Pierre-Francois 
Published: March 2020

Abstract
Introduction. Due to the aberrant deregulation of the CDK4/6-INK4-RB pathway in breast cancer, CDK4/6 inhibitors are now a cornerstone of first line treatment of metastatic breast cancer showing an increase of progression free survival and overall survival. However, resistance to treatment eventually occur. We aimed at deciphering the molecular mechanisms of resistance to CDK4-6 inhibitors and at evaluating associations of therapies that could restore the sensitivity to the treatment. Methods. To identify potential DNA methylation signatures associated with the acquired resistance to CDK4/6 inhibitors, we established a MCF7 model, resistant to CDK4/6 inhibitors that we also used in Swiss nude mice via xenograft experiments. qMSRE were used to analyze the methylation status of genes encoding for BCL2 family members in cells, but also on circulating tumor DNA (ctDNA) in our in vivo model. Results. Using acquired resistant MCF7 cells to CDK4/6 inhibitors, our work demonstrate that these cells harbor a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug. We next discern that DNMT3A and TET2 are the molecular determinants of this phenomenon via the epigenetic modulation of DNA methylation profile of genes encoding for BCL2 family. Using in vivo model, we noted that the ctDNA dynamic of the DNA methylation level of genes encoding for BCL2 family members is associated with the emergence of the resistance to CDK4/6 inhibitor demonstrated by the absence of tumor growth inhibition. Our experiments also indicated that the administration of a BH3-minetic drug at this time point restores the inhibition of tumor growth. Conclusion. This work provides the evidence that epigenetic modulation (methylation level) of key genes detected in ctDNA is associated with resistance to CDK4-6 inhibitors. The BH3-mimetic drugs are seem really appealing in that context.
Citation Format: Jean-Sebastien FRENEL, Deborah Voisin, Arulraj Nadaradjane, Gwenola Bougras-Catron, Mario Campone, Aurelien Serandour, Pierre-Francois Cartron. The acquired resistance of mammary cancer cells to CDK4/6 inhibitors drives a DNA methylation reprogramming of genes encoding for BCL2 family members that confers a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-04-09.
Abstract P4-06-12: Understanding how precancerous lesions progress to breast cancer using mouse models
Authors: Bu Wen , Jiang Weiyu , Li Yi 
Published: March 2020

Abstract
There are distinct cell subpopulations in normal epithelial tissue, including stem cells, progenitor cells, and more differentiated cells, all of which have been extensively studied for their susceptibility to tumorigenesis and intertumoral heterogeneity. However, normal cells usually have to progress through a precancerous lesion state before becoming a full-blown tumor. Precancerous early lesions are heterogeneous too. It remains unclear whether distinct subsets of precancerous cells contribute to the eventual cancer and intertumoral heterogeneity. By using mouse models of breast cancer that are tailored to address this question, we demonstrated that both precancerous stem cells (PcSCs) and more differentiated cells in the precancerous lesion can be induced to form cancer readily upon introduction of constitutively active versions of either HRAS or BRAF. However, the resulting tumors were dramatically different in protein profiles and histopathology: PcSCs gave rise to adenocarcinoma while more differentiated precancerous cells yielded metaplastic carcinoma with severe squamous differentiation and more robust activation of MEK/ERK signaling. In contrast, constitutively activated PIK3CA caused both PcSCs and more differentiated precancerous cells to progress into adenocarcinoma. Therefore, both cell types in precancerous lesions and the genetic mutations that these cells suffer contribute to the characteristics of the resulting cancer. This work identifies previously unknown players in cancer heterogeneity and suggests that cancer prevention should target precancerous cells broadly and not be limited to PcSC.
Citation Format: Wen Bu, Weiyu Jiang, Yi Li. Understanding how precancerous lesions progress to breast cancer using mouse models [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-06-12.
Abstract P4-07-09: Identification and functional analysis of interleukin-1 (IL-1) induced gene expression pattern in breast cancer (BCa) and prostate cancer (PCa) cells
Authors: Nawas Afshan Fathima , Kanchwala Mohammed , Thomas-Jardin Shayna , Dahl Haley , Roos Nicole , Bautista Monica , Wong Ally , Xing Chao , Delk Nikki 
Published: March 2020

Abstract
Breast cancer (BCa) and prostate cancer (PCa) are both hormone receptor (HR) driven cancers with similar etiology, where tumor microenvironment inflammation promotes both BCa and PCa progression. Interleukin-1 (IL-1) is an inflammatory cytokine present in the tumor microenvironment, is elevated in BCa and PCa patient tumor tissue, correlates with poor prognosis, and inversely correlates with HR expression in tumor tissue. We have shown that IL-1 represses the BCa and PCa therapeutic targets, Estrogen Receptor Alpha (ERα) and Androgen Receptor (AR), respectively, in PCa and BCa cell lines; yet the cells remain viable. Thus, we hypothesize that IL-1 induces similar molecular responses in BCa and PCa cells that promote HR independence and subsequent treatment resistance. To address our hypothesis, we performed RNA sequencing of HR positive (HR+) BCa and PCa cell lines treated with IL-1 and compared IL-1-modulated gene expression patterns with the basal gene expression of HR negative (HR-) BCa and PCa cell lines. Our bioinformatics analysis revealed a suite of 350 genes that, based on ontology, promote inflammation response, angiogenesis, oxidative stress response, and cell motility. We chose two IL-1-induced genes from the genes list, p62 and SOX9, for functional analysis. p62 is an antioxidant and autophagy-related scaffold protein and SOX9 is an embryonic transcription factor. We performed p62 and SOX9 siRNA and found that loss of p62 or SOX9 reduce cell viability in HR- cell lines. We also found that the FDA approved p62-targeting drug, verteporfin, reduces cell viability in HR- cells line. Thus, our 350 genes list revealed alternative therapeutic targets for HR-independent cells, including BCa or PCa patients that might evolve HR-independence due to inflammation.
Citation Format: Afshan Fathima Nawas, Mohammed Kanchwala, Shayna Thomas-Jardin, Haley Dahl, Nicole Roos, Monica Bautista, Ally Wong, Chao Xing, Nikki Delk. Identification and functional analysis of interleukin-1 (IL-1) induced gene expression pattern in breast cancer (BCa) and prostate cancer (PCa) cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-09.
Abstract P4-09-13: Spectrum analysis of the inherited mutations of BRCA1/-2 genes that associated with high risk breast cancer in Saudi population
Authors: Hawsawi Yousef MohammedRabaa , Meliti Abdelrazak , Cupler Edward , Sobahy Turki , Zailaie Samar , Baghdadi Mohammed , Alardati Hosam 
Published: March 2020

Abstract
Background: Breast cancer (BC) is the most common prevalent cancer among female worldwide, despite the advances in molecular biology. In Saudi Arabia, the disease represents 19.9% of the total cancer-related deaths in women. Inherited mutations of BRCA1/-2 are well documented to be associated with higher risk of breast cancer.
Aim: To investigate the role of inherited mutation in BRCA1/-2 genes that associated with breast cancer in Saudi population.
Methodology: A total of 41 FFPE samples were collected from BC patients admitted to KFSHRC-Jeddah from 2013 to 2018. Genomic DNA was extracted using the Qiagen FFPE kit. A100ng of each DNA samples were used for library preparation using Ion AmpliSeq™ Library Kit Plus with Saudi Inherited Cancer Panel. Ion Torrent Proton platforms were used for DNA sequencing on Ion Torrent PGM using Ion PI™ Hi-Q™ Sequencing 200 Kit.
Results: A total of 26 distinct heterozygous BRCA1/-2 variants were identified in Saudi population, 15 variants in BRCA1 gene and 11 in BRCA2 gene. In BRCA1, one variant was nonframeshift deletion and 11 were missense, 3 variants likely benign, while in BRCA 2, one was stopgain and 6 were missense and 4 variants likely benign.
Conclusion: Screening of BRCA1/-2 genes mutations helps in understanding the risk associated with mutations of other forms of cancer in Saudi population. The preliminary data is used as an establishing of a high-throughput NGS molecular profiling for Saudi breast cancer patients
Citation Format: Yousef MohammedRabaa Hawsawi, Abdelrazak Meliti, Edward Cupler, Turki Sobahy, Samar Zailaie, Mohammed Baghdadi, Hosam Alardati. Spectrum analysis of the inherited mutations of BRCA1/-2 genes that associated with high risk breast cancer in Saudi population [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-13.
Abstract P4-09-14: Evaluation of the relationship between antioxidant gene polymorphisms and breast cancer
Authors: Topcu Turkan Ozturk , ısıksacan Nilgun , Kilic Zisan Asal , Pehlivan Sacide , Gunaldi Meral 
Published: March 2020

Abstract
Background: Myeloperoxidase (MPO) is a lysosomal enzyme found in monocytes, macrophages and primary granules of neutrophils. MPO participates in the biotransformation reaction of specific carcinogens by catalyzing the formation of hypochloric acid. The destruction of malignant and non-malignant cells is achieved via MPO enzyme. An important mechanism in oxidative stress regulation is the function of uncoupling proteins (UCP), which are among the mitochondrial membrane proteins. They control free radical formation. Theaim of thisstudywastodeterminetherelationshipbetweenpolymorphisms of myeloperoxidase (MPO), uncoupling protein 2 (UCP-2)genesanddevelopment of breastcancer. Methods: Thedistributions of genotypeandallelefrequencywascomparedamongthe groups.Thirty-seven caseswithbreastcancerandseventyhealthycontrolswereenrolled in thepresentstudy. Thestudyfocused on threefunctionalvariants; a variant in a variable number of 27 bp tandem repeatsin a variant in thepromoter region (G463A) of MPO gene and a variant in thepromoterregion(-866G/A) of UCP-2 gene. Wegenotypedthesevariantsusingthepolymerasechainreaction (PCR) and/or PCR- restrictionfragmentlengthpolymorphism (RFLP) method. Thedistribution of alleleand genotype in MPO and UCP-2 geneswerecomparedbetweencaseswithbreastcancer andhealthycontrolsusingchi-square test. Results: Significantlydecreasedbreastcancerriskswerefoundfor UCP-2 AA, and AG polymorphisms(For UCP-2 AA polymorphism OR=8.167; 95%CI:2.785-23.951; p=0.001, for UCP2 AG polymorphism OR=4.341; 95%CI:1.679-11.222; p=0.002).Significantly increasedbreastcancer risk wasfoundfor UCP-2 GG polymorphism (OR:5.0; 95%CI:2.207-11.327; p=0.001).Therewerenostatisticallysignificantdifference in any genotype of MPO whencaseswithbreastcancerandhealthycontrolswerecompared. Conclusion: In the current study, UCP-2 AA, AG and GG genotypes were found to be associated with breast cancer. In contrast, MPO GG, GA genotypes were not associated with breast cancer. Further studies are needed to determine whether these gene polymorphisms have a place in diagnosis or determining the risk of disease.
Citation Format: Turkan Ozturk Topcu, Nilgun ısıksacan, Zisan Asal Kilic, Sacide Pehlivan, Meral Gunaldi. Evaluation of the relationship between antioxidant gene polymorphisms and breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-14.
Abstract P4-10-11: PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials
Authors: Almugbel Fahad A , Saleh Ramy , Ocana Alberto , Pandiella Atanasio , Amir Eitan 
Published: March 2020

Abstract
Introduction: A number of different drugs have been developed to target the PI3 kinase/AKT/mTOR pathway. Most randomized trials in breast cancer have been performed in patients unselected for pathway activation although aberrations of components of this pathway are common. Here we explore the predictive value of PIK3CA and AKT mutations in randomized trials of drugs targeting this signaling route.
Methods: We searched PubMed for randomized trials of drugs targeting the PI3 kinase/AKT/mTOR pathway in metastatic breast cancer. The search was supplemented by a manual search of recent ASCO and ESMO meetings. Eligible studies needed to report efficacy data based on presence or absence of PIK3CA or AKT status measured either in tumor specimens or in circulating DNA. Hazard ratios (HR) for progression-free survival (PFS) in PIK3CA or AKT mutant and wild-type groups were extracted and pooled in a meta-analysis using generic inverse variance and random effects modeling. Sensitivity analyses were performed based on the mechanism of action of the experimental drug.
Results: Of the 15 studies identified, 10 studies comprising of 3615 patients were eligible for analysis. Studies included pan-PI3kinase inhibitors (n=5), alpha-specific PI3kinase inhibitors (n=1), AKT inhibitors (n=2) and mTOR inhibitors (n=2). Approximately 38% of patients had either PIK3CA or AKT mutations. The addition of drugs targeting the PI3 kinase/AKT/mTOR pathway was associated with a significantly longer improvement in PFS in patients with PIK3CA or AKT mutations than in those with wild-type status (HR 0.61, 95% CI 0.50-0.75 versus HR 0.83, 95% CI 0.67-1.02, p for difference = 0.04). Similar results were observed in sensitivity analyses (see Table).
Conclusion: Benefit from drugs targeting the PI3 kinase/AKT/mTOR pathway in breast cancer appears to occur exclusively in those with PIK3CA or AKT mutations. Future trials of these drugs should be designed only in biomarker selected patients.
TableGroupPIK3CA or AKT mutationPIK3CA and AKT wildtypep for differenceHR95% CIHR95% CIExcluding AKT inhibitors0.640.52-0.790.810.63-1.030.16Excluding pan-PI3 kinase inhibitors0.580.47-0.710.710.51-1.150.24Excluding AKT and alpha-specific PI3 kinase inhibitors0.690.48-1.000.980.83-1.150.09Excluding mTOR inhibitors0.620.49-0.800.920.80-1.060.008
Citation Format: Fahad A Almugbel, Ramy Saleh, Alberto Ocana, Atanasio Pandiella, Eitan Amir. PIK3CA status as a predictor of benefit from drugs targeting the PI3K/AKT/mTOR pathway: A meta-analysis of randomized trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-11.
Abstract P4-10-16: Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
Authors: Sonnenblick Amir , Salmon-Divon Mali , Salgado Roberto , Pondé Noam , Loibl Sibylle , Denkert Carsten , Joensuu Heikki , Kellokumpu-Lehtinen Pirkko-Liisa , Azaria Amos , Loi Sherene , Michiels Stefan , Sotiriou Christos 
Published: March 2020

Abstract
Purpose
We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy.
Experimental Design
The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival (DDFS).
Results
Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N=209), were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (HR=1.27 p-interaction=0.014 [DCN], HR=1.58, p-interaction=0.027 [PLAU], HR=1.71, p-interaction=0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR=0.73 p-interaction=0.47 [DCN], HR=0.71, p-interaction=0.73 [PLAU], HR=0.84; p-interaction=0.36 [HER2STROMA]).
Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC &lt;50%).
Conclusions
Reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.
Citation Format: Amir Sonnenblick, Mali Salmon-Divon, Roberto Salgado, Noam Pondé, Sibylle Loibl, Carsten Denkert, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Amos Azaria, Sherene Loi, Stefan Michiels, Christos Sotiriou. Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-16.
Abstract P4-10-31: Patterns of protein expression and signaling assessed by reverse phase protein array (RPPA) in estrogen-receptor negative (ER-), HER2-amplified breast cancer (BC) that was primary-refractory to preoperative (preop) HER2-directed therapy
Authors: Pierobon Mariaelena , Levin Maren K , Baldelli Elisa , Kim Leslie SL , Liotta Lance , Petricoin Emanuel F , O'Shaughnessy Joyce 
Published: March 2020

Abstract
Background: ER- HER2+ BC is comprised of a heterogeneous mix of intrinsic BC subtypes which have differential responsiveness to preop HER2-directed therapies combined with chemotherapy. Patients (pts) with ER- HER2+ BC whose disease progressed while on or who had no response to preop HER2-directed therapy are uncommon and the mechanisms of resistance within this primary-refractory disease are unknown. We utilized RPPA-based protein pathway activation mapping to map the drug target signaling architecture in pts’ primary-refractory ER- HER2+ BCs to begin to assess mechanisms of resistance. Methods: Eight primary-refractory ER- HER2+ FFPE BC tissues obtained from 5 pts (preop biopsies n=4 and/or post-treatment surgical resection n=4) underwent laser capture microdissection to isolate pure tumor epithelium followed by RPPA-based analysis of the levels and/or activation/phosphorylation of approximately 130 key signaling proteins known to be involved in tumorigenesis and metastatic progression. Results: Pts were all treated with preop trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) with no response and/or with progression of disease. Three pts also received preop doxorubicin/cyclophosphamide without response. RPPA-based analysis revealed that post-TCHP surgical samples had higher activation of a number of drug targets including receptor tyrosine kinases (RTK) such as MET and ALK, as well as HER family signaling proteins phospho-HER3 and phospho-EGFR compared to the matched pre-TCHP samples. Conclusions: In these ER- HER2+ BCs that were primary-refractory to preop TCHP, in those pts with patient-matched pre/post treatment samples, activation of several potential resistance pathways such as alternative RKT signaling as well as EGFR and HER3 signaling was observed. These data are hypothesis-generating and require exploration in additional ER- HER2+ primary-refractory tissues.
Citation Format: Mariaelena Pierobon, Maren K Levin, Elisa Baldelli, Leslie SL Kim, Lance Liotta, Emanuel F Petricoin, Joyce O'Shaughnessy. Patterns of protein expression and signaling assessed by reverse phase protein array (RPPA) in estrogen-receptor negative (ER-), HER2-amplified breast cancer (BC) that was primary-refractory to preoperative (preop) HER2-directed therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-31.