bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-04-08: Genomic analysis of breast papillomas
Authors: Elder KJ , Kader T , Hill P , Opeskin K , Goode DL , Pang J-M , Fox SB , Mann GB , Campbell IG , Gorringe KL 
Published: February 2018

Abstract
Background: Papillomas are often found co-existing with breast carcinoma yet they are not considered to be a true precursor of the disease. Previous studies have shown that some cases may carry copy number alterations (CNA) or mutations in AKT1/PIK3CA (Troxell et al., 2010, Modern Pathology 23: 27-37) suggesting this lesion may have malignant potential. To date, a detailed study of both pure papillomas (not associated with cancer) and those seen in the same breast as a carcinoma has not been undertaken. Therefore, we set out to investigate the molecular changes associated with this lesion and whether papillomas can be clonally related to synchronous breast carcinoma.
Method: Papilloma cases were identified from a hospital database and independently reviewed by consultant pathologists followed by micro-dissection of formalin-fixed paraffin-embedded tumour tissue and DNA extraction. For CNA detection either Affymetrix Molecular inversion Probe (MIP) 330K arrays were used or low-coverage whole genome sequencing using 5-10 ng of DNA (Kader et al., 2016, Genome Medicine 8: 121) where there was insufficient DNA for MIP arrays. We applied either of these 2 methods to 24 cases of pure papilloma as well as 20 papilloma with synchronous ductal carcinoma in situ (DCIS) and/or invasive ductal carcinoma (IDC). Additionally, targeted exon sequencing of breast cancer driver genes was performed for a subset of cases.
Results: Among the pure papillomas 31% (5/16) showed CN change with, the most frequent change being 16q loss (2/16). Of the papillomas synchronous with DCIS/IDC analysed to date, 2/5 were shown to be clonal with the co-existing carcinoma. Final CNA analysis will be presented for 24 pure papilloma cases and 20 synchronous cases.
Targeted sequencing revealed that all for pure papillomas analysed to date harboured somatic mutations in PIK3CA (3/4 cases) and PIK3R1 (1/4,) suggesting that most papillomas are driven by alterations in the PI3-kinase/AKT pathway. The final sequencing data to be presented will include an additional 5 pure papillomas and 10 synchronous cases.
Conclusion: Our observation that 40% of papillomas are clonal to breast carcinoma suggests that DCIS or IDC can arise from a common ancestor as co-existing papillomas, however, most papillomas co-existing with carcinoma are likely to be independent in our cohort.
Citation Format: Elder KJ, Kader T, Hill P, Opeskin K, Goode DL, Pang J-M, Fox SB, Mann GB, Campbell IG, Gorringe KL. Genomic analysis of breast papillomas [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-04-08.
Abstract P3-05-05: Class IIa HDAC inhibition promotes an anti-tumor macrophage phenotype that induces breast tumor regression and inhibits metastasis
Authors: Guerriero JL , Sotayo A , Ponichtera HE , Castrillon JA , Pourzia AL , Schad S , Johnson SF , Carrasco RD , Lazo S , Bronson RT , Davis SP , Lobera M , Nolan MA , Letai A 
Published: February 2018

Abstract
While tumor-associated macrophages (TAMs) often have net pro-tumor effects, their embedded location and their untapped potential provide impetus to the discovery of strategies to turn them against tumors. We recently reported that a first in class selective class IIa HDAC inhibitor (TMP195) influenced human monocyte responses to colony stimulating factors CSF-1 and CSF-2 in vitro. Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumor microenvironment and reduces tumor burden and pulmonary metastases through macrophage modulation. TMP195 induces recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumors. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumor reduction. These data introduce class IIa HDAC inhibition as a novel means to harness the anti-tumor potential of macrophages to enhance cancer therapy.
Citation Format: Guerriero JL, Sotayo A, Ponichtera HE, Castrillon JA, Pourzia AL, Schad S, Johnson SF, Carrasco RD, Lazo S, Bronson RT, Davis SP, Lobera M, Nolan MA, Letai A. Class IIa HDAC inhibition promotes an anti-tumor macrophage phenotype that induces breast tumor regression and inhibits metastasis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-05.
Abstract P3-05-07: Improving CAR T cell function by reversing the immunosuppressive tumor environment of breast cancer
Authors: Bajgain P , Tawinwung S , Watanabe N , Sukumaran S , Anurathapan U , Heslop HE , Rooney CM , Brenner M , Leen AM , Vera JF 
Published: February 2018

Abstract
Adoptive transfer of T cells redirected to tumor-associated antigens (TAAs) by expression of chimeric antigen receptors (CARs) can produce tumor responses, even in patients with resistant malignancies. To target breast cancer, we generated T cells expressing a CAR directed to the TAA mucin-1 (MUC1). T cells expressing this CAR (86±1.9%, n=5) specifically killed MUC1-expressing cells (MDA-MB-468 – 45.9±7.3%, MCF-7 – 36.8±3.6) but not MUC1(-) 293T cells (3.7±1.6% specific lysis, 20:1 E:T, n=3). Although these CAR T cells had potent anti-tumor activity against breast cancer cells, when exposed to the Th2-polarizing cytokine IL4 [which is upregulated in tumor samples (Oncomine, p&lt;0.05)] we observed a dramatic reduction in their cytolytic potential [IL2 - 45.9±7.3% vs IL4 - 11.3±3.7% specific lysis, 20:1 E:T ratio, n=4]. Thus, to protect our CAR.MUC1 T cells from the negative influences of IL4, we generated an inverted cytokine receptor (ICR) in which the IL4 receptor exodomain was fused to the IL7 receptor endodomain (4/7 ICR). Transgenic expression of this molecule in CAR.MUC1 T cells (55±4.8% double positive cells, n=5), restored the cytolytic function of CAR T cells (30.9±8.1% specific lysis, 20:1 E:T, n=3). Next, to determine the long term effects of this modification we co-cultured transgenic T cells with MUC1+ tumor cells and measured tumor and T cells numbers. In the presence of IL4, only double positive (CAR.MUC1-4/7) T cells expanded and eliminated the tumors in vitro and in vivo. However, upon tumor elimination, transgenic T cells rapidly contracted, demonstrating the antigen- and cytokine-dependence of the product. In conclusion, CAR.MUC1-4/7 T cells can effectively target breast cancer cells and retain their cytotoxic function even in the IL4-rich tumor microenvironment.
Citation Format: Bajgain P, Tawinwung S, Watanabe N, Sukumaran S, Anurathapan U, Heslop HE, Rooney CM, Brenner M, Leen AM, Vera JF. Improving CAR T cell function by reversing the immunosuppressive tumor environment of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-07.
Abstract P3-05-20: A study on amount, localization and immune phenotype of tumor-infiltrating lymphocytes in different subtypes of breast cancer
Authors: Popovska SL , Dimitrova PD , Dineva TB 
Published: February 2018

Abstract
Objective: The aim of the study was to investigate the localization, amount and type of lymphocytic infiltrate, found in different molecular subtypes of breast cancer (BC).
Methods: Retrospectively, 100 cases of invasive BC were analyzed and immunohistochemicaly (IHC) stratified in four subtypes (Luminal A and Luminal B-like, HER2-positive, and triple negative (TN). The percentage of stromal areas occupied by tumor-infiltrating lymphocytes (TILs) was assessed for H&E slides. The samples were IHC-stained for CD3, CD4, CD8, CD20 and FoxP3. The immunophenotyped lymphocytes - intratumoural and stromal, were separately counted, semi-quantitatively graded and further analyzed.
Results: A total of 10% of all tumors were lymphocyte-predominant BC. Intratumoral and stromal TILs were predominantly CD3+T-lymphocytes. High counts of all subtypes TILs - intratumoral and stromal, were most common for TNBC and HER2-positive BC.
In TNBC, the intratumoral CD3+TILs are significantly related to CD8+ (p=0.002) and FoxP3+ phenotype (p=0.010). In HER2 BC, the intratumoral and stromal CD3+ TILs were significantly related to FoxP3+ phenotype (p = 0,035 and p= 0.011, respectively).
Conclusion:CD3+T-cell mediated immunity, especially the one related to CD8+ and FoxP3+ lymphocytes was the leading one in antitumor response in BC, and high count of intratumoral and stromal lymphocytes predominated in TN and HER2-positive BC.
Key words: Breast cancer, tumor-infiltrating lymphocytes, CD3, CD4, CD8, CD20, FoxP3.
Citation Format: Popovska SL, Dimitrova PD, Dineva TB. A study on amount, localization and immune phenotype of tumor-infiltrating lymphocytes in different subtypes of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-20.
Abstract P3-06-06: Human endogenous retrovirus TROJAN promotes triple negative breast cancer progression and represents a potential therapeutic target
Authors: Jin X , Xu X-E , Jiang Y-Z , Shao Z-M 
Published: February 2018

Abstract
Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. We used RNA-Seq to analyze the transcription level of each HERV loci across the genome in eight pairs of triple negative breast cancer (TNBC) and normal breast tissues. We identified one LTR70, which we dubbed TROJAN, was a TNBC related HERV. We also found that HERVs could not be researched as families because each members from the same family had different expression patterns in TNBC. TROJAN promoted proliferation and invasion in TNBC cells and indicated poor outcomes in patients. Here, we confirmed that TROJAN regulated the progression of TNBC through multiple mechanisms, with ZMYND8, a metastasis-repressing factor, being one of the targets of TROJAN. TROJAN could bind to ZMYND8, promoting its degradation through ubiquitin-proteosome system, and downregulated the transcription level of EGFR, thus stimulating the metastasis of TNBC. The association of TROJAN, ZMYND8, and EGFR was subsequently confirmed in clinical samples. Furthermore, our study verified that the therapeutic delivery of antisense oligonucleotides targeting TROJAN significantly suppressed metastasis of TNBC in vivo. In conclusion, TROJAN promotes the progression of breast cancer and serves as a potential therapeutic target in TNBC.
Citation Format: Jin X, Xu X-E, Jiang Y-Z, Shao Z-M. Human endogenous retrovirus TROJAN promotes triple negative breast cancer progression and represents a potential therapeutic target [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-06.
Abstract P3-06-11: Withdrawn
Authors: Hamy A-S , Val de Lièvre C , Laas E , Darrigues L , Priour M , Guerin J , Balezeau T , Livartowski A , Pierga J-Y , Escalup L , Asselain B , Rouzier R , Lae M , Decroze D , Pinheiro A , Laurent C , Reyal F 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P3-09-01: Withdrawn
Authors: Pollán M , Lope V , Castelló A , Mena-Bravo A , Amiano P , Aragonés N , Fernández-Villa T , Guevara M , Dierssen T , Fernández-Tardón G , Castaño-Vinyals G , Marcos-Grajera R , Moreno V , Salas-Trejo D , Díaz-Santos M , Kogevinas M , Pérez-Gómez B , Priego-Capote F 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P3-12-11: Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model
Authors: Veitch ZW , Khan OF , Tilley D , Kostaras X , King K , Lupichuk S , Tang P 
Published: February 2018

Abstract
Background: Patient adherence to adjuvant hormonal therapy for breast cancer (BC) is correlated with improved survival. Recent publications have demonstrated ethnic disparities in adjuvant hormone adherence (AHA) for privatized healthcare models.
Objective: To identify disparities in AHA for BC patients within a universal healthcare system in Alberta, Canada.
Methods: Patients diagnosed from 2007-2014 with stage I-III, ER+/HER2- BC receiving adjuvant FECD or DC chemotherapy and at least one month of adjuvant hormonal therapy in Alberta, Canada were retrospectively assessed. Hormone monotherapy (tamoxifen, AI), switch strategies (tam to AI), and treatment duration were collected. Compliance was assessed with central pharmacy data. Patient ethnicity was identified using patient first/last and parental last name via Onolytics® ethnographic software. Ethnicity was further verified using a centrally collected place of birth. Age, AJCC stage, psychiatric diagnoses (mood, bipolar), and comorbidity were collected. Log rank and Chi squared were used to assess difference between adjuvant hormonal therapy for variables at 1, 2, and 5 years. Log rank p-values at 2 years are reported.
Results: A total of 2,399 ER+ patients were included for analysis. AHA was non-significant for ethnicity (p=0.797), comorbidity (p=0.623), psychiatric disorders (p=0.145), or elderly cohorts (p= 0.814). AHA by stage was significant with stage III &gt; II &gt; I (p=0.004) having the highest compliance rates. AHA was highest for planned hormonal switch strategies (p=0.004) compared to monotherapy.
Hormone Adherence RatesCharacteristicsNo. of Patients% AdherenceEthnicity Caucasian211891.6Asian15293.4Middle Eastern/African9593.7Hispanic2491.7Age &lt;65207791.8&gt;6534192.1Comorbidity 096191.21-3134392.2&gt;311493Psychiatric Dx Yes31189.7No210792.1Stage I45388.3II151292.1III45394.5Hormone Strategy Monotherapy173190.9Switch68794.2
Conclusion: AHA is not dependent on ethnicity, age, comorbidity, or psychiatric diagnosis in a universal healthcare model. Conversely, higher rates of AHA are seen with planned switch strategy compared to monotherapy, contradictory to the BIG I-98 trial. Patients with higher stage, and thus higher risk of BC recurrence have increased adherence compared to their low risk counterparts. Reinforcement of AHA for low/moderate risk BC patients, in addition to tamoxifen to AI switch strategies may improve overall adherence.
Citation Format: Veitch ZW, Khan OF, Tilley D, Kostaras X, King K, Lupichuk S, Tang P. Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-11.
Abstract P4-02-05: Diagnostic value of breast MRI in evaluating total extent of disease when non-calcified DCIS is present in stereotactic core biopsy samples
Authors: Sheth D , Bao J , Abe H , Jaskowiak N 
Published: February 2018

Abstract
PURPOSE
To compare the extent of disease as seen on mammography, breast MRI and final surgical pathology in all patients with non-calcified DCIS identified on stereotactic core biopsy. Can MRI provide useful diagnostic information to the surgeon when mammographically occult DCIS is present.
METHOD AND MATERIALS
All patients with stereotactic core biopsies performed at the University of Chicago from 2010 to 2017 were retrospectively reviewed. Patients with pathology demonstrating DCIS in non-calcified cores on stereotactic biopsy were further selected based on whether they had a subsequent breast MRI and definitive surgical treatment. A total of 76 patients met these criteria. All patients undergoing stereotactic core biopsy had at least six 9-gauge cores removed, all of which were radiographed and separated based on whether calcifications were present or absent. Select patients with documented DCIS in the non-calcified cores had a MRI. All patients with MRI underwent a routine diagnostic protocol consisting of one pre- and five post-contrast bilateral, fat suppressed T1 sequences along with a non-fat suppressed T2 sequence. Final surgical treatment was subsequently determined and performed by the breast surgeon.
RESULTS
76 women met all criteria for this study. In 16/76 (21%) of the cases, MRI revealed greater extent of disease than was detected via mammography, and led to change in management in half of those cases (8/76 - 11%). In all 16 of these cases, final surgical pathology confirmed the MRI-detected extent of disease. In 52/76 (68%) of the cases, MRI confirmed the extent of disease detected on mammography and final surgical pathology. In 8/76 (11%) of the cases, MRI showed little to no abnormal enhancement at site of mammographically detected calcifications, even though final surgical pathology confirmed presence of residual disease.
CONCLUSION
The presence of non-calcified DCIS in stereotactic core biopsy samples raises the suspicion for the presence of mammographically occult disease. Breast MRI performed in this setting shows that in majority (82% -68/76) of the cases, MRI can either confirm or even advantageously reveal greater extent of disease than was initially detected on mammography. Furthermore, there can be a change in management due to the breast MRI findings.
CLINICAL RELEVANCE/APPLICATION
Breast MRI can be a useful diagnostic tool for the surgeon when non-calcified DCIS is present in stereotactic core biopsy samples.
Citation Format: Sheth D, Bao J, Abe H, Jaskowiak N. Diagnostic value of breast MRI in evaluating total extent of disease when non-calcified DCIS is present in stereotactic core biopsy samples [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-05.
Abstract P4-02-13: Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging breast MRI?
Authors: Benveniste APA , Ebuoma LO , Jonna A , Sam K , Severs FJ , Roark A , Sepulveda KA , Tamara O-P , Sedgwick EE 
Published: February 2018

Abstract
Purpose: Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging Breast MRI?
Materials and Methods: Retrospective review of women diagnosed with breast cancer who underwent a breast MRI for staging of disease was performed at a single institution from October 2012 to September 2015.
Results: Breast MRI for staging was done for 435 patients diagnosed with breast cancer. Ages ranging from 24 to 86 years old (median, 52 years); sizes ranging from 0.5 to 13.5 cm (mean, 3.5 cm). 29 patients (7 %) had biopsy-proven second tumors in the same breast but different quadrant as the primary tumor or in the contralateral breast. From the 435 patients, 304 had minimal/ mild BPE and 103 had moderate/marked BPE (28 missing). Of the patients with an invasive primary cancer and a second tumor in the same breast but different quadrant as the primary tumor or in the contralateral breast, 12 of 29 patients had discordance in subtypes between the primary and secondary tumors (41%) and 17 of 29 had concordance in the subtypes between the primary and secondary tumors (59%). 6.3% (19 out 304) of patients with minimal/ mild BPE had multicentric /bilateral disease and 9.7% (10 out 103) of patients with moderate/ marked BPE had multicentric/ bilateral breast cancer.
Conclusion: 435 patients with recent diagnosis of breast cancer who underwent staging breast MRI for diagnosis of additional sites of disease, 7% was diagnosed with an additional site of cancer. From these group of patients, approximately 6% had other site of disease among patients who had minimal/ mild BPE in the breast MRI versus 10% of patients with moderate/marked BPE. BPE may play a role in the setting of multicentric/ bilateral breast cancer.
Citation Format: Benveniste APA, Ebuoma LO, Jonna A, Sam K, Severs Jr. FJ, Roark A, Sepulveda KA, Tamara O-P, Sedgwick EE. Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging breast MRI? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-13.
Abstract P4-03-14: OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling
Authors: Wu Z , Wang W , Zhang B , Xue J , Chi Y , Wu J 
Published: February 2018

Abstract
Triple-negative breast cancer (TNBC) or Basal-like breast cancer is characterized by worse prognosis than other breast cancer subtypes due to the rapid-arising therapeutic resistance accompanied by aggressive metastasis. The therapy-resistant tumor cells, including cancer stem-like cells (CSCs) with intrinsic resistance or tumor cells acquired resistance during treatments, could repopulate the primary tumors and serve as seeds for recurrent metastatic lesions. However, the molecular events orchestrating the innate and acquired therapeutic resistance are not completely understood. We found a recently identified linear ubiquitin-specific deubiquitinase OTULIN is overexpressed in breast tumors, especially in the basal-like subtype, compared with normal breast tissues. Moreover, OTULIN overexpression significantly increased TNBC cells resistance to chemotherapy and is associated with shorter RFS in breast cancer patients. Mechanistically, we found genotoxic treatments activate OTLULIN, which promotes epithelial-to-mesenchymal transition (EMT) in TNBC cells through increased activity of Wnt/β-Catenin signaling. OTULIN overexpression significantly increased TNBC cells resistance to chemodrugs while inhibiting Wnt/β-Catenin sensitized TNBC xenografts to Doxorubicin treatment in vivo. Our findings suggest that OTULIN-mediated Wnt/β-Catenin activation may increase TNBC therapeutic resistance and aggressiveness by promoting EMT. Targeting OTULIN and the chemotherapy-induced Wnt/β-Catenin activation may serves as promising strategy to mitigate drug resistance and reduce metastasis in TNBC patients receiving chemotherapy.
Citation Format: Wu Z, Wang W, Zhang B, Xue J, Chi Y, Wu J. OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-03-14.