bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-18-10: A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC)
Authors: Howell Sacha J , Kenny Laura M , Lord Simon , Krebs Matthew G , Arkenau Tobias , Baird Richard , MacPherson Iain R , Bahl Ash , Clack Glen , Ainscow Edward , Barrett Anthony GM , Dickinson Paul A , Fuchter Matthew J , Lehnert Manfred , Ali Simak , McIntosh Stuart , Coombes Charles 
Published: March 2022

Abstract
Background: CDK7 inhibition is a promising therapeutic strategy in cancer. CDK7 is a key kinase, regulating cell division, transcription and nuclear receptor function [1]. Although recent advances have been made in the treatment of TNBC this disease is still one of significant unmet need. Materials and Methods: Tolerability and efficacy of Samuraciclib were assessed in a TNBC expansion cohort of the first in human study of Samuraciclib. These patients had metastatic or locally advanced TNBC and had received prior taxane and anthracycline therapy including at least one line of chemotherapy for metastatic or locally advanced disease. Results: From 29th January 2019 to 12th April 2021, 23 women with advanced TNBC were recruited and dosed with Samuraciclib 360mg OD. Treatment has generally been well tolerated with all patients remaining on treatment until disease progression. The most common adverse drug reactions (AE) were: G1-2 Nausea (96%), Vomiting (52%) and Diarrhea (91%). There were 4 dose reductions to manage upper GI adverse events of nausea and/or vomiting. G3 events were as follows: 2 Grade 3 Diarrhea, 1 Grade 3 Vomiting, 1 Grade 3 Fatigue, 1 Grade 3 Stomatitis, 1 Grade 3 Anaemia and 1 Grade 4 Thrombocytopenia21 patients have had follow-up evaluations for assessment of efficacy. Stable disease was achieved in 14 patients, 1 with partial response (being on treatment for 72 weeks) and 7 patients with progressive disease; two additional patients remain on compassionate use treatment, following disease progression by RECIST. 5 patients have been on treatment for at least 24 weeks of whom 3 have exceeded 1 year. Conclusions: Samuraciclib demonstrated an acceptable safety and tolerability profile with evidence of antitumour activity in advanced TNBC. References1.Patel et al. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018. doi: 10.1158/1535-7163.MCT-16-0847. PMID:29545334.
Citation Format: Sacha J Howell, Laura M Kenny, Simon Lord, Matthew G Krebs, Tobias Arkenau, Richard Baird, Iain R MacPherson, Ash Bahl, Glen Clack, Edward Ainscow, Anthony GM Barrett, Paul A Dickinson, Matthew J Fuchter, Manfred Lehnert, Simak Ali, Stuart McIntosh, Charles Coombes. A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-10.
Abstract P1-19-02: Repurposing the FOXO4 senolytic against triple-negative breast cancer
Authors: Putavet Diana , Baar Marjolein , Shi Tao , Lehmann Johannes , Leyten Tim , Bouma Esmee , Khalil Antoine , Vos Harm-Jan , Burgering Boudewijn , Dansen Tobias , Derksen Patrick , de Keizer Peter 
Published: March 2022

Abstract
Metastatic breast cancer is the second most common cause of cancer-related death in women. Triple Negative Breast Cancer (TNBC) has tan especially poor prognosis partly due to these tumors lacking relevant molecular targets. The most commonly mutated gene in TNBC is the tumor suppressor TP53. Mostly, p53 mutations give rise to stably expressed proteins with tumor promoting functions. Therefore, there is an urgent need for therapeutics that can target p53-mutated TNBCs. Here we show that an anti-senescence compound can target metastatic cancers. We found that, in TNBCs, mutant p53 attained a distinctive conformation that has novel oncogenic roles through binding to the transcription factor Forkhead box O (FOXO) 4 sequestered within promyelocytic leukemia (PML) foci. Since these nuclear structures are specific to senescent cells, we tested the senolytic FOXO4 peptide. In cytotoxicity experiments, we found this compound to target TNBCs specifically over other breast cancer subtypes. Most importantly, these compounds decrease metastatic burden in the most commonly-used mouse model for human breast cancer metastasis. In summary, our results demonstrate that mutant p53-driven cancers presented senescent cell-specific characteristics that makes them a great candidate for the FOXO4-directed anti-senescence therapy. We expect that creative repurposing of senolytics to translate to other types of cancer that are driven by mutant p53.
Citation Format: Diana Putavet, Marjolein Baar, Tao Shi, Johannes Lehmann, Tim Leyten, Esmee Bouma, Antoine Khalil, Harm-Jan Vos, Boudewijn Burgering, Tobias Dansen, Patrick Derksen, Peter de Keizer. Repurposing the FOXO4 senolytic against triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-19-02.
Abstract P2-12-06: Pathological response-guided postoperative treatment strategy for positive HR/negative HER2 and positive lymphnodes breast cancer patients with non-responsive pathological results to neoadjuvant chemotherapy
Authors: Yang Yang , Chen Xue , Fan Zhaoqing , He Yingjian , Xie Yuntao , Li Jinfeng , Wang Tianfeng , Ouyang Tao 
Published: March 2022

Abstract
Objective: No consensus up to date suggesting whether patients with positive HR/negative HER-2 and positive lymph nodes breast cancer should receive additional adjuvant chemotherapy following a poor response to neoadjuvant chemotherapy to acquire a better DDFS. The main aim of this trial is to compare the 5-year DDFS between additional adjuvant chemotherapy plus endocrine therapy group and endocrine alone group following 4 cycles neoadjuvant chemotherapy. Method: A multicenter, open-label, randomized, controlled, phase 3 trial was conducted. All patients enrolled in the study were HR+ HER2- LN+ breast cancer patients completing four cycles neoadjuvant chemotherapy, with a non-responsive pathological result to neoadjuvant chemotherapy. The non-responsive criterion was defined as Miller and Payne staging grade1 to grade 3, or any grade of Miller and Payne staging but residual positive lymph nodes were found in surgical specimen. All enrolled patients were randomly assigned to receive four cycles non-cross resistant regimen plus endocrine therapy, or endocrine therapy alone. The primary endpoint was DDFS, and the secondary endpoint was iDFS and OS. Result: From October 2010 to September 2018, a total of 391 patients were enrolled for eligibility. The final ITT analysis compromised 379 patients (187 in adjuvant chemotherapy plus endocrine therapy group, and 192 in endocrine therapy alone group). After a median follow-up of 72.4 months, the 5-year distant disease free survival estimate was 92% (95% CI 88-96) in the adjuvant chemotherapy group and 90% (86-94) in the endocrine therapy alone group (HR 0.79, 95% CI 0.45-1.37) (P=0.401). In the prespecified CEF subgroup, the 5-year DDFS was 94% (95% CI 90-98) in adjuvant chemotherapy group, and 91% (95% CI 87-94) in endocrine group (HR 0.68, 95% CI 0.36-1.30) (P=0.249). In the exploratory analysis, we found a better 5-year DDFS trend in adjuvant chemotherapy group in ypN+ patients in CEF subgroup (P=0.196). Conclusion: A better 5-year DDFS trend in additional adjuvant chemotherapy plus endocrine therapy can be found for patients with positive HR/negative HER-2 and positive lymph nodes following a poor response to neoadjuvant chemotherapy.
Citation Format: Yang Yang, Xue Chen, Zhaoqing Fan, Yingjian He, Yuntao Xie, Jinfeng Li, Tianfeng Wang, Tao Ouyang. Pathological response-guided postoperative treatment strategy for positive HR/negative HER2 and positive lymphnodes breast cancer patients with non-responsive pathological results to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-06.
Abstract P3-03-21: Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean?
Authors: Keymeulen Kristien , Geurts Sandra , Kooreman Loes , Duijm Lucien , Engelen Sanne , Vanwetswinkel Sigrid , Luiten Ernest , Siesling Sabine , Voogd Adri , Tjan-Heijnen Vivianne 
Published: March 2022

Abstract
Background: For patients with ductal carcinoma in situ (DCIS), data about contralateral breast cancers detected by MRI at primary diagnosis and the impact of MRI use on the incidence and stage of contralateral breast cancers during follow-up are scarce. Methods: We selected all women diagnosed with a primary DCIS in the Netherlands in 2011-2015 from the Netherlands Cancer Registry. The synchronous and metachronous detection of contralateral DCIS and contralateral invasive breast cancer was assessed for patients who did receive an MRI upon primary diagnosis (MRI group) and for an age-matched control group without MRI. Incidence of contralateral disease during follow-up was calculated using competing risk methods.Results: Of the 8486 patients diagnosed with primary DCIS, 1571 (19%) received an MRI. In the MRI group, 0.8% of patients were diagnosed with a synchronous contralateral DCIS and 1.3% with synchronous contralateral invasive breast cancer. Median follow-up time was 6.4 years (IQR: 5.1-7.6). The estimated five-year cumulative incidence of synchronous plus metachronous contralateral DCIS was 2.0% (95% CI: 1.4%-2.8%)) for the MRI group and 0.9% (95% CI: 0.5%-1.5%) for the age-matched control group. The five-year cumulative incidence of contralateral invasive breast cancer was 3.5% (95% CI: 2.7%-4.5%) for the MRI group and 2.3% (95% CI: 1.6%-3.1%) for the age-matched control group. In patients aged &lt;50 years, the cumulative incidence of metachronous contralateral DCIS was statistically significantly higher in the MRI group than in the age-matched controls (sHR= 4.22 (95%CI: 1.19-14.99), P=0.03). This was not the case in patients aged 50-74 years (sHR=0.89 (95%CI: 0.41-1.93), P=0.77). Conclusions: MRI led to more frequent detection of synchronous contralateral invasive breast cancers without lowering the number of metachronous contralateral invasive breast cancers. In patients aged below 50 years, MRI added to conventional imaging led to a persisting higher rate of DCIS diagnosed in the opposite breast, also without influencing the occurrence of invasive breast cancers being detected during the first five years of follow-up. Footnotes
Citation Format: Kristien Keymeulen, Sandra Geurts, Loes Kooreman, Lucien Duijm, Sanne Engelen, Sigrid Vanwetswinkel, Ernest Luiten, Sabine Siesling, Adri Voogd, Vivianne Tjan-Heijnen. Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-21.
Abstract P3-09-17: Systems-scale characterization of the human immunome in breast cancer for precision medicine
Authors: Yi Stephen 
Published: March 2022

Abstract
It becomes more clear that many deleterious cancer mutations could exhibit a 'gain-of-function' (GOF) behavior. Systematic investigation of such mutations has been lacking and largely overlooked. Advances in next-generation sequencing have identified thousands of genomic variants that perturb the normal functions of proteins, further contributing to diverse phenotypic consequences in breast cancer. Alterations in immune-related pathways are common hallmarks of cancer. A comprehensive understanding of how cancer mutations rewire immune signaling networks and functional output in breast cancer is instrumental to realize the full potential of immunotherapy. Here, we systematically interrogated somatic mutations involved in immune signaling that alter immune responses in cancer patients. To do so, we developed a network-based integrative model to prioritize potential immune responder genes. Identified mutations were enriched in essential protein domains and genes identified were associated with responsiveness to multiple immunotherapy modalities. These genes were used to devise an interactome network propagation framework integrated with drug-associated gene signatures to identify potential immunomodulatory drug candidates in breast cancer. Together, our systems-level analysis results help interpret the heterogeneous immune responses among patients and serve as a resource for future functional studies and targeted breast cancer therapeutics. This study is significant and innovative, as it demonstrates that integration of multi-omics data can help identify critical molecular determinants for effective targeted therapeutics.
Citation Format: Stephen Yi. Systems-scale characterization of the human immunome in breast cancer for precision medicine [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-17.
Abstract P3-18-14: Assessment of quality of life and objective cosmetic outcome of breast conserving surgery with or without latissimus dorsi mini-flap in breast cancer
Authors: Kim Jang-il , Han Yireh , Lim Changjin , Cheun Jong-Ho , Jung Ji Gwang , Kim Hong Kyu , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik 
Published: March 2022

Abstract
Introduction : Latissimus dorsi mini-flap (LDMF) with breast conserving surgery (BCS) was introduced as a useful volume replacement technique when the tumor is located in upper or outer portion of breast and the tumor size is large requiring extensive excision of breast tissue. However few studies have assessed quality of life (QoL) and objective cosmetic outcome of LDMF in breast cancer surgery. We tried to evaluate those in patients who underwent BCS with or without LDMF. Methods : This study was a prospective, single-center cohort study of patients who underwent LDMF and BCS between 2011 and 2018. As a control, patients who underwent BCS without any volume replacement and the tumor size equal to or greater than 2.5cm on the upper or upper outer of the breast on preoperative imaging. Breast Q questionnaire and body photo were taken at least 1 year after surgery. Two breast surgeons and one plastic surgeon who did not performed LDMF assessed the cosmetic outcome of the patients with photo. Results : 62 patients were in the BCS with LDMF group and 58 patients were in BCS-only group. Pathologic tumor size was significantly larger in LDMF group than BCS-only group (LDMF 3.89cm vs BCS-only 2.92cm, p= 0.001 ). Psychosocial well-being (P= 0.024), physical well-being (P= 0.000), and satisfaction with surgeon (p= 0.006) were significantly better in the BCS-only group than in the LDMF group respectively. But, there were no significant difference in neither sexual well-being (p= 0.286) nor satisfaction for breast (p=0.278) between BCS and LDMF group. In the physicians assessment, there was no significant difference in the cosmetic outcome score between the two groups (LDMF 2.56/4 vs. BCS-only 2.58/4, p= 0.884). Conclusion : In conclusion, physician assessed cosmetic outcome of LDMF was equivalent to that of BCS without LDMF although the tumor size was significantly larger in patients with LDMF. Some inferiority of QoL might be due to postoperative pain or arm movement discomfort. We are planning to evaluate objective cosmetic results using BCCT.core software.
Citation Format: Jang-il Kim, Yireh Han, Changjin Lim, Jong-Ho Cheun, Ji Gwang Jung, Hong Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han. Assessment of quality of life and objective cosmetic outcome of breast conserving surgery with or without latissimus dorsi mini-flap in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-14.
Abstract P4-02-08: Amcenestrant in combination with CDK4/6 inhibitor palbociclib demonstrates synergistic anti-tumor activity in ER+ endocrine-resistant breast cancer xenograft models
Authors: Shomali Maysoun , Guo Zhuyan , Cheng Jane , Sullivan Amy , El-Ahmad Youssef , Sun Fangxian , Sidhu Sukhvinder , Lee Joon Sang , Cai Hui , Pollard Jack , Debussche Laurent , Soria Chris , Bouaboula Monsif 
Published: March 2022

Abstract
Nearly 70% of newly diagnosed cases of breast cancer (BC) are estrogen receptor positive (ER+) where endocrine therapy is a primary treatment. Despite initial efficacy seen with endocrine therapies, approximately 40% of patients develop acquired resistance which ultimately limits the use of these agents even as most of these tumors continue to require ERα. The strategies to combat these cancers with resistance are not yet defined and represent the next major clinical challenge in ER+ breast cancer. Amcenestrant is an optimized oral SERD (selective estrogen receptor degrader) with potent antagonist and degradation activity irrespective of ESR1 mutational status, and is currently being evaluated as monotherapy and in combination with CDK4/6 inhibitors and other targeted therapies for ER+ breast cancer patients in clinical trials. Here, we report that in preclinical models, amcenestrant achieved significant anti-tumor efficacy/regression as a monotherapy and strong synergistic activity when administered together with the CDK4/6 inhibitor, palbociclib, in subcutaneously xenografted endocrine resistant ER+ BC mouse models: ESR1-Y537S mutant-driven MCF7 tumor and HCI-013 PDX (patient-derived xenograft). Transcriptional profile analysis of xenograft tumor biopsies revealed the modulation of different pathways by SERD and palbociclib and highlighted crosstalk of ER and CDK4 signaling pathways. Interestingly, CDK4/6 inhibition by palbociclib induces partial activation of ER pathways as potential mechanism of tumor escape which is completely abolished by the combination treatment of amcenestrant with palbociclib. Early clinical data also showed that amcenestrant in combination with palbociclib, exhibited a favorable safety profile and encouraging antitumor activity in patients with endocrine resistant, ER+/HER2-, advanced breast cancer, which supports its potential to become a new endocrine backbone therapy for ER+ HER2- breast cancer. In conclusion, amcenestrant is an oral SERD, which exhibits significant anti-tumor activity as a single agent and shows synergistic activity with CDK4/6 inhibitor palbociclib in ER+ BC xenografts preclinically and in early clinical development.
Citation Format: Maysoun Shomali, Zhuyan Guo, Jane Cheng, Amy Sullivan, Youssef El-Ahmad, Fangxian Sun, Sukhvinder Sidhu, Joon Sang Lee, Hui Cai, Jack Pollard, Laurent Debussche, Chris Soria, Monsif Bouaboula. Amcenestrant in combination with CDK4/6 inhibitor palbociclib demonstrates synergistic anti-tumor activity in ER+ endocrine-resistant breast cancer xenograft models [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-02-08.
Abstract P4-05-13: Prognostic implication of Yin Yang 1 (YY1) overexpression in patients with primary breast cancer
Authors: Cha Chihwan , Park Hosub , Kim Chul Geun , Chung Min Sung 
Published: March 2022

Abstract
Background: YY1 is conserved transcriptional factor that highly expressed in various types of cancers. It regulates differential epigenetic pathways and protein modifications. However, there is still unknown whether YY1 overexpression has any prognostic significance in breast cancer patients. In this study, we evaluated YY1 expression levels using tissue microarrays and analyzed clinicopathologic characteristics with survival outcomes. Methods: Clinical information and tissue blocks were obtained retrospectively from 491 patients who underwent surgery at Hanyang University Hospital between 2002 and 2016. Immunohistochemical staining was performed using rabbit monoclonal antibody (ab-109237). YY1 expression was determined using H-score. Overexpression was defined as H-score ≥ 28.4 (mean value). Overall survival (OS) and disease-free survival (DFS) was analyzed by Kaplan Meier analysis. Results: Of 491 patients with primary breast cancer, 138 (28.1%) patients had YY1 overexpression. Luminal subtype (ER+/HER2-), early tumor stage, and low grade tumor were significantly associated with overexpression (P&lt;0.0001). In patients with luminal subtype, overexpression was significantly correlated with early nodal stage and low proliferation index (Ki-67≤20%, P=0.014). After median follow up 67 months, YY1 overexpression was significantly associated with better prognosis (OS rates; 96.4% vs. 88.1%, P=0.038 and DFS rates; 92.0% vs. 79.2%, P=0.014). In luminal subtype, patients with overexpression showed better DFS (93.0% vs. 80.2%, P=0.043). In a Cox proportional hazards model, YY1 overexpression was independent significant prognostic factor after adjustment of ER/HER2 status and tumor size (hazard ratio; 0.5, 95% CI [0.26-0.98], P=0.042). Conclusion: YY1 overexpression is a better prognostic marker in patients with primary breast cancer, especially in luminal subtype.
Citation Format: Chihwan Cha, Hosub Park, Chul Geun Kim, Min Sung Chung. Prognostic implication of Yin Yang 1 (YY1) overexpression in patients with primary breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-13.