bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-01-14: Influence of radiotherapy on residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status in breast cancer patients
Authors: Schott Dorothea , Pizon Monika , Pachmann Ulrich , Pachmann Katharina , Mäurer Matthias 
Published: March 2020

Abstract
Background: Preclinical studies have suggested that radiotherapy followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. Radiation induces immunogenic changes in cancer cells which can lead to adaptive up-regulation of PD-L1 expression. Moreover, radiotherapy reduces not only local recurrence but even more distant relapse indicating its influence also on the residual occult tumor such as circulating tumor cells. For this reason the aim of this study was to determine the PD-L1 status on CETCs before and during radiotherapy.
Methods: CETCs were determined in 54 primary breast cancer patients in early and locally advanced stages. The number of CETCs and their expression of PDL-L1 were investigated using the maintrac method. The fraction of PD-L1 positive CETCs was assessed prior to (baseline), 3 and 6 weeks after the start of radiotherapy.
Results: We found an association between the PD-L1 status on CETCs and aggressiveness of cancer disease before radiotherapy. Patients with positive lymph node status had more PD-L1 positive CETCs as compared to patients with negative lymph nodes (mean 73 vs. 50, p&lt;0.01). HER2 expression of the primary tumor was also positively correlated with PD-L1 expression. Lower numbers of CETCs were detected in patients who had not received chemotherapy or adjuvant chemotherapy before radiation than in those who received neoadjuvant chemotherapy (median 20 vs 25 vs 120 CETC/100µl blood, p&lt;0.001). Surprisingly, the fraction of PD-L1 positive CETC decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy.
Conclusion: The number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy and radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients.
Citation Format: Dorothea Schott, Monika Pizon, Ulrich Pachmann, Katharina Pachmann, Matthias Mäurer. Influence of radiotherapy on residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status in breast cancer patients [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 P4-01-14.
Abstract P4-03-01: Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict the status of pathologic response
Authors: Große Regina , Lebioda Antonia , Saegenschnitter Jana , Nguyen Tin Dao , Zentgraf Holger , Buchmann Joerg , Fathke Christine , Steer Susanne , Thomssen Christoph 
Published: March 2020

Abstract
Introduction: Neoadjuvant breast cancer therapy trials have documented impressive rates of pathologic complete response (pCR) of up to 70% and above, depending on grade, hormone receptor and HER2 receptor status and type of therapy. The purpose of our prospective single institution trial is to examine the predictive value of a standardized vacuum assisted core-needle biopsy (VAB) of the tumor site after neoadjuvant therapy with respect to pathologic response status.
Methods: From 2011-2017, all patients who had completed neoadjuvant breast cancer therapy at our institution were informed about this trial regardless of their clinical response status. In case of consent, a VAB of the clip-marked tumor site was performed directly before the operation. At least 3, in most cases 6 biopsy cylinders were obtained.
Results: A total of 113 patients completing neoadjuvant therapy consented to the trial. Four patients presented with bilateral breast cancer, resulting in 117 cases of breast cancer. The pCR rate (ypT0ypN0) was 36% (n=42). In 14 cases, the biopsy did not show any sign of residual disease, although residual disease was detected upon operation, resulting in an accuracy of 88% for correct prediction of pathologic response. Pre-operative VAB correctly predicted residual tumor in 81%. The negative predictive value was 75%.
Conclusions: Although the results of this trial are encouraging, a false negative rate of 19% is entirely insufficient. The method may be useful in guiding decisions regarding the modification of neoadjuvant therapy based on pathological response. Whether or not correct prediction of pathologic response may be improved by further standardizing the tumor marking procedure as well as better defining and increasing the volume of tissue removal by VAB should be examined in a further prospective trial. The omission of operative therapy in case of pCR in a preoperative biopsy after completion of NACT cannot be recommended.
Citation Format: Regina Große, Antonia Lebioda, Jana Saegenschnitter, Tin Dao Nguyen, Holger Zentgraf, Joerg Buchmann, Christine Fathke, Susanne Steer, Christoph Thomssen. Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict the status of pathologic response [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 P4-03-01.
Abstract P4-06-10: Lentiviral signaling reporters uncover tumor-initiating cell heterogeneity in breast cancer patient-derived xenografts
Authors: Landua John , Gong Ping , Lewis Michael 
Published: March 2020

Abstract
Classical markers of tumor-initiating cells (TIC), aldehyde dehydrogenase 1 (ALDH1) activity and the cell-surface markers, CD44pos/CD24low/neg, show insufficient cell type specificity to identify TIC definitively, nor do they allow robust enrichment by FACS. As a consequence, analyses of TIC function and gene expression to date are not definitive. Identification and characterization of the TIC subpopulation is critically important in breast cancer since these cells are thought to mediate treatment resistance, as well as local and distant recurrence. This is particularly critical for “triple negative” breast cancer (TNBC), since currently there are no targeted therapies available for this clinical subtype. Lentiviral signaling reporter vectors allow purification of enriched TIC subpopulations thereby facilitating single cell analyses to identify distinct sets of cells with TIC features. We used a collection of fluorescent lentiviral reporters that enable visualization and flow cytometric enrichment of cells undergoing STAT3-, GLI-, WNT-, or OCT4/SOX2-mediated transcriptional activity. Our collection of patient derived xenograft (PDX) models of TNBC were infected with the lentiviral reporters, re-transplanted, and screened for reporter activity upon regrowth. TIC function of reporter-expressing cells relative to negative cells was assayed by mammosphere formation and limiting dilution transplantation. Reporter expressing cells with enriched TIC function were then analyzed by single cell RNAseq for expression of classical markers to identify the subset of cells most likely to represent the TIC subpopulation. Our results indicate that STAT3 and GLI transcriptional activity can serve as uniquely PDX-dependent indicators for TIC function for a subpopulation of cancer cells. Also, multiple potential TIC signaling pathways, including STAT3, GLI, and OCT4/SOX2, can be active in a single PDX model, but do not necessarily associate with TIC function, indicating TIC diversity in TNBC. These data in conjunction with treatment response and single-cell RNA-seq sheds light on the molecular diversity of TIC populations in TNBC, identifies candidate targets for therapeutic intervention, and will indicate whether TIC diversity is associated with differential response to different chemotherapeutic agents.
Citation Format: John Landua, Ping Gong, Michael Lewis. Lentiviral signaling reporters uncover tumor-initiating cell heterogeneity in breast cancer patient-derived xenografts [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 P4-06-10.
Abstract P4-08-03: Tumor suppressors p53 and ARF control ADAR1-driven tumorigenicity in triple negative breast cancer
Authors: Kung Che-Pei , Kuzmicki Catherine E , Bross Emily A , Ryu Sua , Freeman Eric , Sabloak Thwisha , Bramel Emily R , Maggi Leonard B , Weber Jason D 
Published: March 2020

Abstract
Research Overview and Objective Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant challenge. The co-deficiency of tumor suppressors p53 and ARF is a significant genetic signature enriched in TNBC, but it is not yet clear how TNBC is regulated by this genetic alteration. Methods To answer this question, we established p53/ARF-defective murine embryonic fibroblast (MEF) to study the molecular and phenotypic consequences in vitro. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. Results Increased transformation capability was observed in p53/ARF-defective cells, and formation of aggressive mammary tumors was also seen in p53−/−ARF−/− mice. RNA-editing enzyme ADAR1 was identified as a potential mediator for the elevated oncogenic potential. Interestingly, we found that the overexpression of ADAR1 is also prevalent in human TNBC cell lines and patient specimen. Using short hairpin RNA (shRNA) to reduce ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. Different levels of RNA editing of known ADAR1 targets were detected in shRNA-treated human TNBC cell lines, suggesting that ADAR1-mediated RNA editing contributes to TNBC pathogenesis. Implication/Discussion These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, partially through affecting ADAR1-mediated RNA editing. Further understanding of this pathway could shed light on potential vulnerabilities of TNBC and inform the development of personalized therapies based on patients’ genetic signiatures.
Citation Format: Che-Pei Kung, Catherine E Kuzmicki, Emily A Bross, Sua Ryu, Eric Freeman, Thwisha Sabloak, Emily R Bramel, Leonard B Maggi Jr, Jason D Weber. Tumor suppressors p53 and ARF control ADAR1-driven tumorigenicity in triple negative 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 P4-08-03.
Abstract P4-14-06: Express model of hereditary multigene mutation analysis in breast cancer patients
Authors: Grinshpun Albert , Carmon Einat , Kaduri Luna , Zick Aviad , Shkedi Shiri , Shalom Edna , Granit Avital , Monas Liza , Shaldovsky Tamar , Hamburger Tamar , Meiner Vardiella , Peretz Tamar 
Published: March 2020

Abstract
Introduction
Traditionally, women with family history of breast and ovarian cancer, or young age at presentation, are referred to BRCA1\2 mutation testing. The growing information regarding other genes involved in predisposition to breast cancer (regardless of specific family history) and the potential impact of germline alterations on surgical and oncologic management led us to establish a model to perform a quick multigene mutation evaluation among breast cancer patients at our cancer institute.
Methods
All breast cancer patients that required genetic counselling (according to treating oncologist/surgeon’s judgement) were referred, after thorough explanation and signing informed-consent forms, to a 'genetic coordinator' and 'genetic nurse'. They provided each patient with a second pre-test explanation and ordered wide hereditary cancer gene panel (83-genes, Invitae). Results were given within 2-4 weeks. All patients\results were registered centrally at our center and discussed at routine Onco-genetic Multidisciplinary Board (OMB). A referral for formal genetic counselling is offered to all patients, and rapid track is arranged for patients with positive results.
Results
During a 12-months pilot period, 130 breast cancer patients were examined via the model, and 109 results were received; 44 patients (41%) had no abnormal findings, 50 patients (45%) had variants of uncertain clinical significance, and 15 patients (14%) were found carriers of pathogenic variants (ATM n=2, BRCA1 n=1, BRCA2 n=2, CHEK2 n=3, MUTYH n=1, PALB2 n=2, RAD50 n=1, RECQL4 n=1, TP53 n=2). Among this group, 3 patients (20%) had immediate panel-driven treatment decisions: Mastectomy to avoid radiotherapy (RAD50 carrier), oophorectomy during lumpectomy (BRCA2 carrier), and bilateral risk-reducing mastectomy instead of lumpectomy (TP53 carrier).
Conclusions
The creation of an Express-model for broad germline analysis allows to obtain rapid and meaningful results with impact on treatment. We believe that the Express-model should be considered as an integral tool of multimodal care of breast cancer patients.
Citation Format: Albert Grinshpun, Einat Carmon, Luna Kaduri, Aviad Zick, Shiri Shkedi, Edna Shalom, Avital Granit, Liza Monas, Tamar Shaldovsky, Tamar Hamburger, Vardiella Meiner, Tamar Peretz. Express model of hereditary multigene mutation analysis in breast cancer patients [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 P4-14-06.
Abstract P4-14-09: Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis
Authors: Saleh Ramy , Nadler Michelle B , Desnoyers Alexandra , Fazelzad Rouhi , Amir Eitan 
Published: March 2020

Abstract
Background: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established.
Methods: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting (neoadjuvant vs. adjuvant) and study design (retrospective vs. randomized controlled trials). When available, odds ratios (OR) for commonly reported safety and tolerability measures such as treatment-related death, treatment discontinuation without progression, dose reduction, neuropathy, renal impairment and hematological toxicity were calculated.
Results: Seven studies comprising 1699 patients met the inclusion criteria. Median follow up was 54.5 months. All studies reported DFS and 4 studies reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.53-0.96; P = 0.03). However, OS was no different with a higher number of events in the platinum-based treatment arm (HR 1.17, 95% CI 0.81-1.69; P = 0.42). There was no significant difference between treatment settings (p = 0.74) or between study designs (p = 0.74), although a higher HR for OS was observed for studies in the adjuvant (HR 1.34, 95% CI 0.54-3.35) compared to neoadjuvant setting (HR 1.14, 95% CI 0.76-1.70). The reporting of toxicity was suboptimal with most studies not reporting safety and tolerability metrics clearly. Platinum-based treatment was associated with more neutropenia and thrombocytopenia and treatment discontinuation, however, the magnitude of this effect could not be estimated accurately.
Conclusions: Platinum-based treatment improves DFS but has no effect on OS and increases toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. The higher magnitude of discordance in adjuvant compared to neoadjuvant studies suggests an effect of platinum-based therapy on loco-regional control prior to surgery rather than prevention of distant metastatic disease. Platinum-based chemotherapy cannot be recommended in unselected patients with TNBC.
Citation Format: Ramy Saleh, Michelle B Nadler, Alexandra Desnoyers, Rouhi Fazelzad, Eitan Amir. Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis [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 P4-14-09.
Abstract P5-04-27: The relationship between tumour associated macrophage markers and tumour, demographic & behavioural factors in breast cancer
Authors: Singh Urvashi , Castle John , Greenhalgh Sophie , Hussain Umar , Descamps Tine , Nash Sarah , Wilson Mary , Hunt Roger , Kirwan Cliona C 
Published: March 2020

Abstract
BACKGROUND: Tumour associated macrophages (TAMs) are prognostic markers in breast cancer, however the influence of patient demographic and behavioural factors on these inflammatory markers has not been fully appreciated.
METHODS: In 201 invasive breast cancer and 58 ductal carcinoma in-situ (DCIS) patients, TAM density (percentage % CD68 [IHC-immunohistochemistry] positive cells) was correlated with tumour factors (grade, proliferation (Ki67), ER, HER2); demographic factors (age, menopausal status, breast density, BMI, diabetes) and behavioural factors (smoking, alcohol).
RESULTS: TAM density was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour (59%, 41% and 6% respectively; p&lt;0.001). In invasive cancer, TAM density increased with increasing tumour grade (Grade 1: 42%, Grade 2: 58%, Grade 3: 72%; p=0.006), high Ki67 (71% vs. 47%; p=0.004), ER negativity (70% vs. 51%; p=0.02) and HER2 (HER2 positive 77% vs. HER2 negative 55%; p=0.055). TAM density was higher in high compared to low/intermediate DCIS (44% % vs 31% respectively).
In terms of demographic factors, TAM density did not correlate with age, menopausal status, breast density (BIRADs), BMI or history of diabetes. TAM density was not increased in patients who smoked; however, it was increased in patients who self-reported alcohol intake (non-drinker 43% vs. drinker 62%; p=0.01).
CONCLUSION: TAM density shows utility in identifying aggressive breast cancer sub-types. The association reported between TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer.
Citation Format: Urvashi Singh, John Castle, Sophie Greenhalgh, Umar Hussain, Tine Descamps, Sarah Nash, Mary Wilson, Roger Hunt, Cliona C Kirwan. The relationship between tumour associated macrophage markers and tumour, demographic & behavioural factors in 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 P5-04-27.
Abstract P5-06-20: Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-positive early breast cancer
Authors: Tajiri Wakako , Sugii Azusa , Ijichi Hideki , Ueo Hiroki , Koga Chinami , Nakamura Yoshiaki , Okamoto Masahiro , Taguchi Kennichi , Tokunaga Eriko 
Published: March 2020

Abstract
&lt;Background&gt; The Clinical Treatment Score post-5 years (CTS5) is a prognostic tool to estimate the residual risk of distant recurrence (DR) after 5 years of endocrine therapy in postmenopausal women with estrogen receptor (ER)-positive breast cancer. (J Clin Oncol, 2018; 19: 1941-1947). CTS5 might be useful to decide the indication of extended adjuvant endocrine therapy after 5years. &lt;Purpose&gt; This study was conducted to elucidate the usefulness of CTS5 for the prediction of late DR in postmenopausal women with ER-positive early breast cancer treated in our department. &lt;Patients and Methods&gt; CTS5 was calculated in 377 postmenopausal patients with ER-positive breast cancer who underwent surgery between 2003 and 2009. They had received 5-year adjuvant endocrine therapy without DR. CTS5 is stratified into three groups; low, intermediate and high risk of DR. The relationships between CTS5 and the clinicopathological characteristics and prognosis were evaluated. &lt;Results&gt; According to CTS5, 202 (53.6%), 104 (27.6%) and 71 (18.8%) patients were divided into low, intermediate and high-risk of late DR groups. In the CTS5-high risk group, significantly more positive lymph nodes (p&lt;0.0001), larger tumor size (p&lt;0.0001), higher histological grade (p&lt;0.0001), more administration of adjuvant chemotherapy (p&lt;0.0001), more administration of adjuvant endocrine therapy of Aromatase inhibitor (AI) (p=0.0029), more visceral distant metastasis (p=0.0029), lower ER expression (p=0.0064) were observed. Significantly lower incidence of DR was observed in CTS5-low risk group. Thus, CTS5 was significantly prognostic for late DR. Intriguingly, in the CTS5-low risk group, administration of endocrine therapy of AI (p=0.0023), lower histological grade (HG1, 2; p=0.0011), ER high expression (TS; 6-8 p=0.0002), and positive PgR (p=0.0007) were significantly better DR-free survival (DRFS). &lt;Conclusion&gt; CTS5 demonstrated clinical validity for predicting late DR in this study cohort. IN the CTS5-low risk group, the incidence of late DR was significantly lower than that of in CTS5-intermediate or high risk group. The low CTS5 might be useful to decide the indication of 5-year adjuvant endocrine therapy in the postmenopausal patients with ER-positive early breast cancer.
Citation Format: Wakako Tajiri, Azusa Sugii, Hideki Ijichi, Hiroki Ueo, Chinami Koga, Yoshiaki Nakamura, Masahiro Okamoto, Kennichi Taguchi, Eriko Tokunaga. Usefulness of CTS5 for the prediction of late distant recurrence in postmenopausal women with estrogen receptor-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 P5-06-20.