bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD15-04: Trop-2 inactivation of E-cadherin drives triple negative breast cancer relapse
Authors: Alberti Saverio , Trerotola Marco , Relli Valeria , Lattanzio Rossano , Ceci Martina , Boujnah Khouloud , Garbo Valeria , Moschella Antonino , Querzoli Patrizia , Pedriali Massimo , Antolini Laura , Guerra Emanuela 
Published: February 2021

Abstract
Hundreds of proteins/genes have been linked to the metastatic phenotype. However, consistent markers of tumour aggressiveness and metastatic potential in breast cancer patients were not identified, not even including proteomic analysis and large-scale genome sequencing.Metastasis-associated genes were predicted to include not only drivers of the metastatic phenotype, but also secondary events, together with adaptive, counterbalancing changes. Thus, to identify candidates with a required role in metastatic diffusion, we looked for genes that were concordantly dysregulated across orthogonal cancer metastasis settings. This led us to identify Trop-2 as uniquely upregulated and associated to metastasis in experimental models of breast cancer, as well as in other solid tumors. We identified functional inactivation of E-cadherin by Trop-2 as the main motor of metastatic diffusion of such metastatic systems. Trop-2 binding to E-cadherin inactivated its cell-cell adhesion function, through release from the cytoskeleton, for activation of β-catenin transcriptional activity. This led to anti-apoptotic signaling, increased cell migration capacity and enhanced cancer cell survival. We showed that this mechanism led to metastatic diffusion of xenotransplants growing in immunosuppressed mice. An E-cadherin-inactivation metastasis program was then shown to be recapitulated in breast cancer patients, as well as in other solid tumors, over 24 independent case series, encompassing 13,042 primary tumours. Aggressive triple-negative breast cancers were shown to be driven toward global relapse by Trop-2 overexpression, through E-cadherin inactivation and activation of β-catenin transcriptional activity. No disease recurrence was observed in control cases over +12 years of follow-up. These finding lead to a novel paradigm of a Trop-2-driven, E-cadherin-inactivation program as a main metastasis driver in solid tumors. This may open far-reaching perspectives in diagnostic procedures and anti-cancer therapies.
Citation Format: Saverio Alberti, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, Patrizia Querzoli, Massimo Pedriali, Laura Antolini, Emanuela Guerra. Trop-2 inactivation of E-cadherin drives triple negative breast cancer relapse [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 PD15-04.
Abstract PD15-07: Myc regulates alternative splicing through a network of RNA binding proteins in breast cancer
Authors: Urbanski Laura , Angarola Brittany , Brugiolo Mattia , Yurieva Marina , Park Sunghee , Anczukow Olga 
Published: February 2021

Abstract
The oncogenic transcription factor MYC is one of the most frequently altered genes in cancer and is highly dysregulated in aggressive tumor types, including triple negative breast cancer (TNBC). Although direct targeting of MYC or its regulators in human tumors has proved difficult, the undisputed clinical relevance of this transcription factor warrants continued study for therapeutic targeting of MYC-driven processes in tumors. Recently, we and others have shown the tumorigenic capacity of MYC is critically dependent on the RNA splicing machinery and on several splicing factor RNA-binding proteins (RBPs). Dysregulation of alternative mRNA splicing, a key step in gene expression regulation, is a hallmark of cancer, and can lead to the expression of isoforms driving tumor initiation, progression or drug resistance. Understanding which component(s) of the RNA machinery are regulated by MYC, and the functions of MYC-induced spliced isoforms, may reveal new targets that circumvent prior failures of directly targeting MYC.
Here, we examine MYC-induced changes in gene expression and alternative splicing through RNA-sequencing of breast cell lines and tumors. Using a mammary epithelial cell line with an inducible MYC system, we identified over 4,000 MYC-induced alternative splicing events as well as 378 MYC-induced RBPs. Co-expression network analysis of these RBPs in TCGA breast tumor RNA-seq data uncovered 8 RBP modules, four of which are highly correlated with MYC activity and highly expressed in TNBC. One of these modules is preserved across almost all other TCGA tumor types and remains highly correlated with MYC activity, suggesting a pan-cancer role of this co-expression module. We are now defining the functional role of these RBP modules in MYC-driven tumorigenesis in breast cancer models, as well as identifying their downstream oncogenic splicing targets. Our research project will define the role and regulation of alternative splicing in breast cancer, and more specifically in aggressive tumor types such as TNBC. Our findings will provide mechanistic insight into the role of MYC-driven splicing in tumor maintenance and will uncover novel therapeutic targets for MYC-active tumors.
Citation Format: Laura Urbanski, Brittany Angarola, Mattia Brugiolo, Marina Yurieva, Sunghee Park, Olga Anczukow. Myc regulates alternative splicing through a network of RNA binding proteins in 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 PD15-07.
Abstract PD8-05: Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer
Authors: Haricharan Svasti , Punturi Nindo , Seker Sinem , Devarakonda Vaishnavi , Kalra Rashi , Chen Ching-Hui , Mazumder Aloran , Li Shungqiang , Primeau Tina , Ellis Matthew , Kavuri Shyam 
Published: February 2021

Abstract
Estrogen receptor positive (ER+) breast cancer is a leading cause of cancer-related death globally. Resistance to standard of care endocrine treatment occurs in at least 30% of ER+ breast cancer patients resulting in ~40,000 deaths every year in the US alone. Preclinical studies strongly implicate activation of growth factor receptor, HER2 in endocrine treatment resistance of ER+ breast cancer that is HER2- at diagnosis. However, clinical trials of pan-HER inhibitors in ER+/HER2- patients have disappointed, likely due to a lack of predictive biomarkers. Here we demonstrate that loss of MLH1, a principal mismatch repair gene, causally activates HER2 in ER+/HER2- breast cancer upon endocrine treatment. Additionally, we show that HER2 activation is indispensable for endocrine treatment resistant growth of MLH1-defective cells in vitro and in vivo. Consequently, inhibiting HER2 restores sensitivity to endocrine treatment in multiple experimental models including patient-derived xenograft tumors. Patient data from multiple clinical datasets (TCGA, METABRIC, Alliance (Z1031) and E-GEOD-28826) supports an association between MLH1 loss, HER2 upregulation, and sensitivity to trastuzumab in endocrine treatment-resistant ER+/HER2- patients. These results provide strong evidence that MLH1 could serve as a first-in-class predictive marker of sensitivity to combinatorial treatment with endocrine drugs and HER2 inhibitors in endocrine treatment-resistant ER+/HER2- breast cancer patients. Implications of this study extend beyond breast cancer to Lynch Syndrome cancers.
Citation Format: Svasti Haricharan, Nindo Punturi, Sinem Seker, Vaishnavi Devarakonda, Rashi Kalra, Ching-Hui Chen, Aloran Mazumder, Shungqiang Li, Tina Primeau, Matthew Ellis, Shyam Kavuri. Mismatch repair deficiency predicts response to HER2 blockade in HER2-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 PD8-05.
Abstract PS1-31: Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy
Authors: Wang Xin , Wang Wenyan , Liu Jiaxiang , Meng Xiangzhi , Liu Jiaqi , Guo Changyuan , Song Ying , Cui Ningyi , Li Qiao , Xing Zeyu , Wang Jie , Zhang Menglu , Feng Kexin , Wang Pilin , Wang Xiang 
Published: February 2021

Abstract
Background: Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). ALN status is an important prognostic factor for choosing the type of axillary lymph node surgery. Many patients with axillary pCR could replace axillary lymph node dissection (ALND) with sentinel lymph node biopsy (SLNB). Our goal is to develop a new predictive clinical model to detect axillary pCR after NAC and provide clinical clues for avoiding ALND. Methods: A retrospective series of 547 patients who had biopsy-proven positive ALNs at diagnosis from 2007 to 2014 in National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences were involved. We analyzed the clinicopathologic features and developed a nomogram to predict the probability of ALN pCR. Univariate assessment was performed using chi-square test. A multivariate logistic regression stepwise model was used to generate a nomogram to predict ALN pCR in node positive patients. The receiver operating characteristic (ROC) curve was established and the area under the curve (AUC) was calculated to evaluate the accuracy of the model. Internal validation was estimated using 50-50 hold out validation method. Nomogram was validated externally with the prospective cohorts of 167 patients from 2016 to 2018 of Cancer Hospital of Chinese Academy of Medical Sciences and 75 patients from 2018 to 2019 of Beijing Tiantan hospital.Results: In the retrospective study, 172 (31.4%) patients achieved axillary pCR after NAC. Multivariate analysis indicated that clinical nodal (N) stage, hormone receptor (HR) status and clinical response of primary tumor after NAC were significant independent predictors for axillary pCR (P&lt;0.05). The AUCs of the internal validation for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.862 and 0.766, respectively.Conclusion: We developed a nomogram to predict axillary pCR in node positive breast cancer patients after NAC. The predictive model performed well in prospective external validation. This practical tool could provide information to surgeons about whether to avoid ALND after NAC.
Citation Format: Xin Wang, Wenyan Wang, Jiaxiang Liu, Xiangzhi Meng, Jiaqi Liu, Changyuan Guo, Ying Song, Ningyi Cui, Qiao Li, Zeyu Xing, Jie Wang, Menglu Zhang, Kexin Feng, Pilin Wang, Xiang Wang. Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy [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 PS1-31.
Abstract PS1-37: Reduction mammoplasty in the setting of neoadjuvant chemotherapy
Authors: Hewitt Kelly , Wu Susan , Barnes Laura , Yang Joanna , Piper Merisa 
Published: February 2021

Abstract
Background: Oncoplastic reduction mammoplasty is an accepted method of breast conserving surgery that also allows for potentially improved symmetry and aesthetics compared to other techniques and allows for larger tissue volumes to be removed with acceptable cosmetic outcomes. Neoadjuvant systemic chemotherapy (NAC) is increasingly used for the treatment of patients with breast cancer. While there is some data that oncoplastic reduction may delay timing of adjuvant radiation, we sought to examine this in our patients, and specifically to compare complications and time to radiation in patients who received NAC to those that didn’t.
Methods: A retrospective analysis was done of all patients with DCIS or invasive cancer who underwent a reduction mammoplasty and received adjuvant radiation at our single institution from 2009-2018. Patients who received NAC were compared to those that did not.
Results: A total of 114 patients underwent reduction mammoplasty as part of their oncologic surgery and received adjuvant radiation at our institution. Of those, 40.4% received neoadjuvant chemotherapy and 49.1% received no neoadjuvant treatment. A total of 38 patients (33.3%) had some postoperative complication with 8.8% having a serious complication that required intervention. Adjuvant radiation started after 8 weeks in 74.6% of patients and after 12 weeks in 38.6% of patients, with the majority of these delays due to non-clinical factors. A total of 29.4% of patients had a delay due to wound healing issues. There was no association between NAC and delayed radiation due to wound healing (p=0.18).
Discussion: Oncoplastic reduction mammoplasty is a safe option for breast-conserving surgery in patients who have received NAC. The receipt of NAC in itself does not delay timing of adjuvant radiation or lead to increases in delayed wound healing. We are additionally examining other factors and their possible interaction with NAC, including diabetes, smoking, BMI and breast reduction size. In those with larger tumors receiving NAC who would otherwise not be candidates for breast conserving surgery, oncoplastic reduction should be considered as an appropriate option for surgical management. Reduction also allows for wider excision which may mitigate the impact of the longer time from surgery to radiation.
Citation Format: Kelly Hewitt, Susan Wu, Laura Barnes, Joanna Yang, Merisa Piper. Reduction mammoplasty in the setting of neoadjuvant chemotherapy [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 PS1-37.
Abstract PS1-55: Clipping of involved axillary lymph nodes before Neo adjuvant chemotherapy may improve in identification rates & staging of axilla in breast cancer
Authors: Elahi Mohammad Bilal , Bichoo Raouef Ahmed , Grover Kartikae , Khalifa Eiman , Ihsan Naila Bint , Kneeshaw Peter J , Wooler Brendan Paul , Dumitru Dorin , Roychaudhury Ronjabati , Rahman Ayesha , Mahapatra Tapan Kumar 
Published: February 2021

Abstract
Introduction: Neo adjuvant chemotherapy is increasingly being employed in breast cancer to reduce tumour size & down stage axilla. To reduce false negative rates in axillary lymph nodes after down staging with chemotherapy and to improve axillary conservation ultrasound guided clips were placed in involved axillary lymph nodes prior to commencement of NACT. The study aimed at whether preoperative lymph node clipping had any benefit in identification of lymph node after NACT.Methods: This is a single centre study of 55 patients (Mean age 53 years) with invasive breast cancer with biopsy proven involved lymph nodes (T1-3 N1) who underwent ultrasound guided axillary marker clip insertion before start of NACT. If Post chemotherapy imaging showed normal lymph nodes patients underwent SLNB with additional Lymph Nodes sampled to achieve a total of 4 lymph nodes. All sampled nodes were x rayed at the time of surgery to identify marker clip.Results: We had no procedure related complications with insertion of marker clip in any patients. The median number of nodes was 4.0. Average lymph nodes retrieved was 4.9. SLNB was identified in 47/55 patients (85.5%). Median number of sentinel nodes was 3.0 (Range 1-7) Marker was identified in 41/55 patients (74.5%) 30 (54.5%) patients had marker in sentinel node and 11 (20%) patients had marker in non-sentinel node. Histologically clip was reported in 21 (51.2%) patients. Overall pathological complete response (pCr) in axilla was seen 31/55 (56.45%). Tumours with Her2 over expression showed pCr in axilla 83% n=19/23 while triple negative tumours showed pCr in axilla 64% n=9/14. Er+ Her2- tumours showed low pCr rate 16.7% n=3/18. Completion axillary clearance was performed in 14/24 patients and 10/24 received radiotherapy to axilla.Conclusions: Clips in axillary lymph nodes are safe & relatively easy to deploy without any increased morbidity. Our clip identification rate (74.5%) co relates with other well-known publications (Caudel et al 80%, Z1071-76%). Our study findings validate that clip placement improves the identification of involved lymph nodes and hence improve the accuracy of limited axillary dissection in staging axilla.
Citation Format: Mohammad Bilal Elahi, Raouef Ahmed Bichoo, Kartikae Grover, Eiman Khalifa, Naila Bint Ihsan, Peter J Kneeshaw, Brendan Paul Wooler, Dorin Dumitru, Ronjabati Roychaudhury, Ayesha Rahman, Tapan Kumar Mahapatra. Clipping of involved axillary lymph nodes before Neo adjuvant chemotherapy may improve in identification rates & staging of axilla in 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 PS1-55.
Abstract PS1-60: Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit
Authors: Mansour Fatima , Meilak Joseph , Kabeer Kirti , Gowda Manoj , Jafferbhoy Sadaf , Marla Sekhar , Gopalan Vallipuram , Narayanan Sankaran , Soumian Soni 
Published: February 2021

Abstract
Introduction: Neoadjuvant chemotherapy (NACT) is increasingly utilised in the treatment of aggressive breast cancers. There are concerns that this could impact patient recovery following extensive oncoplastic procedures. The literature regarding this is limited and conflicting. We aimed to assess the impact of neoadjuvant chemotherapy on patients undergoing immediate breast reconstructions.
Method: A 5-year retrospective single centre audit of prospectively collected data on patients undergoing immediate breast reconstruction following NACT, was completed. The oncoplastic procedures performed included myocutaneous and perforator flaps, therapeutic mammoplasty and implant based reconstruction. Demographic data, length of stay, biochemical measurements, rates of wound infection, haematoma, explantation rates and return to theatre, were collected. For comparison a matched cohort of patients who underwent primary reconstruction without NACT, during the same period, was selected.
Results: One hundred and fourteen patients were included in the study (52 post NACT vs 62 controls). There were 52% that underwent implant based reconstruction, 33% flaps and 15% mammoplasties. Overall, the NACT group appeared to have slightly improved outcomes including lower complication rates (19% vs 23%, p= 0.042) and length of stay (1.45 vs 1.59 days, p&gt;0.05). Hypoalbuminemia (25.0%) and low WCC (65.2%) were significantly higher in the NACT group but this was not associated with increased complication rates. Conclusion: Our audit suggests that NACT does not cause a significant increase in post-operative morbidity. Further studies with larger numbers will be required to validate these results.
Citation Format: Fatima Mansour, Joseph Meilak, Kirti Kabeer, Manoj Gowda, Sadaf Jafferbhoy, Sekhar Marla, Vallipuram Gopalan, Sankaran Narayanan, Soni Soumian. Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit [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 PS1-60.
Abstract PS1-66: Current practice in implant-based breast reconstruction: A french long-term follow-up study
Authors: Pauly Lea , Couturaud Benoit , Reyal Fabien 
Published: February 2021

Abstract
Background: There is a lack of data on the use of breast implants and the path of patients reconstructed after breast cancer in France. This study aims to identify the paths of patients reconstructed by breast implant in France and assess their impact on survival, but also estimate the quality of the reconstruction, determined by early removal or replacement of implants.Methods : We performed a multicentric retrospective cohort study on women who underwent immediate or delayed implant-based reconstruction after curative or prophylactic mastectomy between 2002 and 2010 in three French private health institutions of public interest.Results : We identified 9 care pathways according to the type of disease, the type of surgery, the addition or not of adjuvant radiotherapy, and the timing of reconstruction. Theses courses concern 2,499 patients, and 3,191 breasts on which at least one implant has been placed. Five implant brands were mainly used during this period: PIP, Mentor, Allergan, Sebbin, and Perthese - with a total of 4,106 implants. The median of follow-up is 6 years [0 ;12 ;1]. The number of implants per breast is significantly different according to the reconstruction pathways (p&lt;0.001). The overall survival and removal incidence of implants are significantly different according to the differents profiles of reconstruction (Log-Rank test: p &lt;0.001).Conclusion : The profiles of patients reconstructed by implants are very heterogeneous, according to their disease, their surgery, the adjunction of adjuvant radiotherapy, and the reconstruction time. This leads to very differents overall survival and breast implants removal rates. By identifying specific pathways despite the heterogeneity of the population, this study makes it possible to identify patients at risk more precisely and to have a more global vision on implant reconstruction in France in the 2000s, over a decade of PIP breast implant use.
Citation Format: Lea Pauly, Benoit Couturaud, Fabien Reyal. Current practice in implant-based breast reconstruction: A french long-term follow-up 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 PS1-66.