bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO2-14-11: Proteogenomic approaches for the identification of NF1/neurofibromin-depleted estrogen receptor positive breast cancers for targeted treatment
Authors: Kim Beom-Jun , Zheng Ze-Yi , Lei Jonathan , Holt Matthew , Chen Anran , Peng Jianheng , Fandino Diana , Singh Purba , Kennedy Hilda , Dou Yongchao , Chica-Parrado M Rosario , Bikorimana Emmanuel , Ye Dan , Wang Yunguan , Hanker Ariella , Mohamed Nada , Hilsenbeck Susan , Lim Bora , Asirvatham Jaya Ruth , Sreekumar Arun , Zhang Bing , Miles George , Anurag Meenakshi , Ellis Matthew , Chang Eric 
Published: May 2024

Abstract
NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking both pathways by fulvestrant (F), a selective ER degrader (SERD), together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models. We aimed to establish approaches to determine how NF1 protein levels impact B+F treatment response to improve our ability to identify B+F sensitive tumors. We examined a panel of ER+ PDX models by DNA and mRNA sequencing and found that more than half of these models carried an NF1 shallow deletion and generally have low mRNA levels. Consistent with RAS and ER activation, RET and MEK levels in NF1-depleted tumors were elevated when profiled by mass spectrometry (MS) after kinase inhibitor bead pull-down. MS showed that NF1 can also directly and selectively bind to palbociclib-conjugated beads, aiding quantification. An immunohistochemistry (IHC) assay was also established to measure NF1, but the MS-based approach was more quantitative. Combined IHC and MS analysis defined a threshold of NF1 protein loss in ER+ breast PDX, below which tumors regressed upon treatment with B+F. These results suggest that we now have a MS-verified NF1 IHC assay that can be used for patient selection as a complement to somatic genomic analysis.
Citation Format: Beom-Jun Kim, Ze-Yi Zheng, Jonathan Lei, Matthew Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, M Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella Hanker, Nada Mohamed, Susan Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew Ellis, Eric Chang. Proteogenomic approaches for the identification of NF1/neurofibromin-depleted estrogen receptor positive breast cancers for targeted treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-11.
Abstract PO2-25-02: The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer
Authors: Wang Hai 
Published: May 2024

Abstract
Immunotherapy has achieved limited success in patients with triple-negative breast cancer (TNBC), an aggressive disease with a poor prognosis. Commensal microbiota have been proven to colonize the mammary gland, but whether and how they modulate the tumor microenvironment remains elusive. We performed a multiomics analysis of a cohort of patients with TNBC (n = 360) and found genera under Clostridiales, and
the related metabolite trimethylamine N-oxide (TMAO) was more abundant in tumors with an activated immune microenvironment. Patients with higher plasma TMAO achieved better responses to immunotherapy. Mechanistically, TMAO induced pyroptosis in tumor cells by activating the endoplasmic reticulum stress kinase PERK and thus enhanced CD8+ T cell-mediated antitumor immunity in TNBC in vivo. Collectively, our findings offer new insights into microbiota-metabolite-immune crosstalk and indicate that microbial metabolites, such as TMAO or its precursor choline, may represent a novel therapeutic strategy to promote the efficacy of immunotherapy in TNBC.
Citation Format: Hai Wang. The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-02.
Abstract PO2-26-06: Prognostic factors pregnancy associated breast cancer: one year versus two years
Authors: Izquierdo Maxim , Baulies Sonia , Ara Carmen , Garcia Maria , Fargas Fransec , Fabregas Rafael , Tresserra Fransec , S Pere Barri 
Published: May 2024

Abstract
Aims: The trend of delayed delivery, the number of women with breast cancer during a pregnancy or in the years after pregnancy is expected to increase Pregnancy breast cancer confers a worse prognostic. Study if the interval pregnancy breast cancer more one year to two years influences the prognostic factors like pregnancy breast cancer one year after Methods: Study 1186 patients with breast cancer and prognostic factors. Analyze delivery before breast cancer, and the interval of last childbirth, one year, more one year to two years and more two years, with prognostic factors (nodes, estrogen receptor, progesterone receptor, HER2 receptor and Ki 67) Results: Breast cancer pregnancy one year after were in 37 patients, more one year to two years in 25 patients and more two years in 491 patients. Positive nodes one year after were in 21 patients, more one year to two year were in seven patients (p &lt; 0'05), and more two years in 155 patients (p=ns). There are not differences (p=ns) in estrogen receptor, progesterone receptor and Ki67, one year versus more one year to two years and more to two years. HER2 and histologic grade there are not differences (p=ns) in one year after versus more one year to two years, but there are differences (p &lt; 0’05) versus more two years Conclusion: Interval last childbirth breast cancer more than one year to two years influences prognostic factors for later breast cancer, and not have differences with prognostic factors than pregnancy one year after
Citation Format: Maxim Izquierdo, Sonia Baulies, Carmen Ara, Maria Garcia, Fransec Fargas, Rafael Fabregas, Fransec Tresserra, Pere Barri S. Prognostic factors pregnancy associated breast cancer: one year versus two years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-26-06.
Abstract PO3-03-09: Clinical Significance of Grade in Triple Negative Breast Cancer
Authors: Malik Mah-noor , Ramanan Neya , Upneja Sarang , Brackstone Muriel , Porter Lisa , Fifield Bre-Anne , Hamm Caroline 
Published: May 2024

Abstract
Triple negative breast cancer (TNBC) is a heterogeneous cancer type that lacks receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor-2 proteins (HER-2). An important prognostic factor for breast cancer patients is the tumour grade, which is the degree of cell proliferation or differentiation of the tumour cells from normal cells. In our initial study involving 305 TNBC patients from 2004-2017 at Windsor Regional Hospital Cancer Centre, we found a statistically significant difference between grade 2 and grade 3 patients, with grade 2 predicting significantly inferior progression-free and overall survival. In our initial study, the overall survival rates for grade 1, 2, and 3 tumours were 90.12%, 64.4%, and 77.2% respectively (p = 0.019) with relapse rates of 70%, 55.6%, and 75.6% respectively (p = 0.04). Our current study is an attempt to validate these initial findings by expanding our data set to include data from the London Health Sciences Centre. A literature review on TNBC and grade was conducted, followed by a retrospective chart review for 305 TNBC patients from the Windsor Regional Hospital and 515 TNBC patients from the London Health Sciences Centre. The parameters for data collection included patient demographics, tumour demographics, therapies, and patient outcomes. We calculated all patient stages using both American Joint Committee on Cancer 7th edition (AJCC7) and the updated AJCC8 staging systems. Initial review of the data supports our earlier findings with a relapse rate of 12.5% in patients with grade 3 tumours and 17% in patients with grade 1 and grade 2 tumours. The completed data set will be analyzed and presented at the conference. Validating our previous findings of significantly inferior patient outcomes for grade 2 compared to grade 3 patients may alter the staging system used for TNBC patients.
Citation Format: Mah-noor Malik, Neya Ramanan, Sarang Upneja, Muriel Brackstone, Lisa Porter, Bre-Anne Fifield, Caroline Hamm. Clinical Significance of Grade in Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-09.
Abstract PO3-23-04: Patient-reported outcomes and complication profiles of implant-based breast reconstruction in patients with postmastectomy radiation therapy
Authors: Liu Jian , Chen Cong , Chen Honggang , Xiang Aizhai , Zheng Ruzhen , Hu Shufang , Guo Jufeng , Qu Li , Zhou Jun , Wu Jiong 
Published: May 2024

Abstract
Objective: This study aims to investigate the patient-reported outcomes (PROs) and complications of distinct implant-based breast reconstruction (IBBR) modality for patients with postmastectomy radiation therapy (PMRT).
Methods: A retrospective review was conducted on breast cancer patients with stage II-III disease who performed IBBR following with PMRT between September 2016 and April 2022. The patients were categorized into two matched groups: (1) patients receiving prepectoral breast reconstruction (PBR) or subpectoral breast reconstruction (SBR) followed by PMRT; (2) patients undergoing PMRT with the tissue expander (PMRT-TE) or permanent implant (PMRT-PI) groups. PROs were measured with BREAST-Q questionnaire. Early and late complications were recorded and analysed.
Results: A total of 55 eligible patients were recruited. For PROs, patients underwent PBR reported significantly higher Satisfaction with Breasts scores (P = 0.003) compared with SBR group, and PMRT-TE group presented higher Satisfaction with Breasts (P = 0.001) but lower Physical Well-being (P = 0.029) scores compared with PMRT-PI group. Moreover, Patients in SBR cohort had a higher risk of capsular contracture (Baker grade III or IV) (20.5% vs 6.3%) and implant dislocation (48.7% vs 12.5%) than patients in PBR cohort. Patients in PMRT-PI group had a slightly higher rate of capsular contracture (Baker grade III or IV) than PMRT-TE group (20.8% vs 12.9%).
Conclusions: PBR was associated with lower rates of late complications, especially for implant dislocation, and higher Satisfaction with Breasts scores compared to SBR. In addition, compared to PMRT-TE with PMRT-PI, patients in PMRT-TE cohort reported superior patient-reported outcomes of Satisfaction with Breasts.
Table 1. Patient and Tumor Characteristics of 55 Patients Stratified with Prepectoral/Subpectoral and PMRT-TE/PMRT-PI Reconstructive Procedure. XX- XX
Table 2. Patient-Reported BREAST-Q Scores XX- XX
Table 3. Association of Reconstruction Techniques with Late Complications. XX- XX
Citation Format: Jian Liu, Cong Chen, Honggang Chen, Aizhai Xiang, Ruzhen Zheng, Shufang Hu, Jufeng Guo, Li Qu, Jun Zhou, Jiong Wu. Patient-reported outcomes and complication profiles of implant-based breast reconstruction in patients with postmastectomy radiation therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-04.
Abstract PO3-23-10: Continued treatment with CDK4/6 inhibitors slow tumor progression by extending G1-phase duration in drug resistant populations
Authors: Armand Jessica , Kim Sungsoo , Yang Hee Won 
Published: May 2024

Abstract
CDK4/6 inhibitors (CDK4/6i) have significantly improved the prognosis of patients with metastatic hormone receptor-positive breast cancer. However, the development of drug resistance leads to the discontinuation of CDK4/6i treatment. The potential benefits of maintaining CDK4/6i treatment in the context of resistance and their underlying molecular mechanisms remain elusive. Here we show that despite tumor progression, continued treatment with CDK4/6i notably extends the G1 phase in drug-resistant cells, thereby slowing their growth. Our single-cell data reveal that the duration of the G1 phase in these resistant cells is approximately tripled under continuous CDK4/6i treatment compared to conditions with CDK4/6i withdrawal, while the durations of the S and G2 phases remain comparable. The maintenance of CDK4/6i induces an alternative inactivation of the retinoblastoma (Rb) protein in drug-resistant cells through its post-translational degradation. However, this alternative form of Rb inactivation is ineffective and thus induces slow activation kinetics of E2F transcription factors, significantly delaying G1 progression. The beneficial effect of maintaining CDK4/6i treatment was further validated in breast cancer xenograft models. Furthermore, our findings suggest that given the spectrum of various CDK4/6i, switching between different CDK4/6i types after the emergence of drug resistance may further delay tumor progression. This study provides new mechanistic insights into the maintenance of CDK4/6i treatment despite the development of drug resistance.
Citation Format: Jessica Armand, Sungsoo Kim, Hee Won Yang. Continued treatment with CDK4/6 inhibitors slow tumor progression by extending G1-phase duration in drug resistant populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-10.
Abstract PO3-24-03: Cisplatin synergizes immune checkpoint blocking through RNFT1 mediated PD-L1 recycling in Triple Negative Breast Cancer
Authors: Chu Jiahui , Zhang Yifan , Hua Yijia , Gong Jue , Mei Jie , Fu Ziyi , Yi Yongmei 
Published: May 2024

Abstract
Since chemotherapy showed synergies with PD-1/PD-L1 blockage therapy in solid tumors, the efficacy in triple negative breast cancer (TNBC) varies greatly and only a subset of patients achieves durable responses. To increase their clinical efficacy, it is important to explore the underlying mechanisms of immune checkpoint ligand PD-L1. Here, we found cisplatin influenced the controlled intracellular transport of PDL1 by inducing the RNFT1-mediated endoplasmic reticulum autophagy. Overexpression of RNFT1 increases the endocytosis-recycling rate of the plasm membrane PD-L1, which is regulated by K63-polyubiquitination and endoplasmic reticulum autophagy degradation of PD-L1, thereby having negative impact on antitumor immunotherapy, such as reduced effective drug concentration and avoiding immune surveillance. Genetically or pharmacologically modulating RNFT1-induced K63 polyubiquitination blocks endocytosis of PD-L1, consequently enhances the antitumor response to PD-L1 blockade. Thus, our results suggest that cisplatin treatment is involved in RNFT1-induced K63 polyubiquitination of PD-L1 endocytosis-recycling pathway that governs immune response, and blocking RNFT1 might enhance the efficacy of PD-1/PD-L1 blockade. These studies have high application and translational potential in triple-negative breast cancer.
Citation Format: Jiahui Chu, Yifan Zhang, Yijia Hua, Jue Gong, Jie Mei, Ziyi Fu, Yongmei Yi. Cisplatin synergizes immune checkpoint blocking through RNFT1 mediated PD-L1 recycling in Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-24-03.
Abstract PO4-09-03: Environmental Metal Exposures and Breast Cancer Risk: A Prospective Study of Nationally Representative Canadian Data
Authors: Pullella Katherine , Lubinski Jan , Hanley Anthony , Harris Shelley , Narod Steven , Kotsopoulos Joanne 
Published: May 2024

Abstract
Introduction: The impact of metal exposure on breast cancer risk remains unclear. Studies have explored metals independently with limited investigation into chronic exposures and mixture analyses. This project describes exposure to eight heavy and essential metals and evaluates the association between metals and breast cancer risk, independently and in a mixture, among Canadian women.
Methods: Demographic information and concentrations of urinary or blood metal biomarkers from 2007-2017 of the Canadian Health Measures Survey (CHMS) were analyzed. Incident breast cancers were ascertained through linkage to the Canadian Cancer Registry. Metal exposure was described using weighted percentiles and categorized by tertiles. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for metal exposure and breast cancer risk. Quantile g-computation was used to estimate the joint association between metal exposure and breast cancer risk.
Results: This analysis included 5,100 women (mean age 44.6 years) with an average follow-up of 6.6 years. Higher urinary arsenic (&gt; 13.0 µg/L) and cadmium (&gt; 10.0 µg/L) had a significant increased risk of breast cancer (HR Arsenic T3 vs. T1 = 2.05; 95%CI 1.05-3.94; HR Cadmium T3 vs. T1 = 1.71; 95%CI 1.01 – 5.87). Analyses into the joint association between the metal exposure mixture and breast cancer risk are ongoing, and matrix results will be presented.
Conclusion: This represents the first evaluation of metal exposure and breast cancer risk in a nationally representative cohort. Our findings suggest that arsenic and cadmium, even at low levels, may be associated with an increased risk of breast cancer. These findings can inform population-level interventions to reduce the burden of cancer in Canada.
Citation Format: Katherine Pullella, Jan Lubinski, Anthony Hanley, Shelley Harris, Steven Narod, Joanne Kotsopoulos. Environmental Metal Exposures and Breast Cancer Risk: A Prospective Study of Nationally Representative Canadian Data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-03.
Abstract PO4-20-02: A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia in early breast cancer
Authors: Zha Xiaoming , Wang Jue , Xu Yinggang , He Jinzhi , Wang Ye , Zhang Weiwei , Wan Xinyu , Shi Wenjie 
Published: May 2024

Abstract
Background: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) injection time is still referred as recombinant human granulocyte CSF (rhG-CSF) as a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. The trial examined whether PEG-rhG-CSF injection on day 7 following chemotherapy was superior to injection on day 3.
Patients and methods: Patients with early breast cancer were randomly assigned to receive a preventive injection on days 7 or 3 following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n=80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction.
Results: Compared with the control group, the white blood count (WBC) or absolute neutrophil count (ANC) in the experimental group was higher on days 9 and 13 (P &lt; 0.05) after chemotherapy, and the incidence of grade 3–4 neutropenia was lower (P = 0.038). The experimental group met the standard for lowering the PEG-rhG-CSF dose were more than that in the control group (69.74% vs. 35.06%, P &lt; 0.001). Patients receiving a lower PEG-rhG-CSF dose had higher WBC count and ANC after chemotherapy, but were more likely to suffer from mild arthralgia. (P &lt; 0.05).
Conclusion: In comparison with PEG-rhG-CSF injection on day 3 after chemotherapy, the incidence of grade 3–4 myelosuppression is lower, and the safety is more manageable after the injection on day 7. Thus, more patients will receive dose reduction and lower patient medical costs.
Citation Format: Xiaoming Zha, Jue Wang, Yinggang Xu, Jinzhi He, Ye Wang, Weiwei Zhang, Xinyu Wan, Wenjie Shi. A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia in early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-02.
Abstract PO4-22-08: Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study
Authors: Kang Byeongju , Lee Jeeyeon , Chae Yee Soo , PARK Ho Yong , Jung Jin Hyang 
Published: May 2024

Abstract
Background
Targeted axillary sampling (TAS) is a new surgical concept for the assessment of axillary lymph node status in breast cancer that is hypothesized to be more effective at minimizing postoperative morbidities than axillary lymph node dissection (ALND), provided the metastatic axillary lymph node can be accurately detected without missing data; however, the oncologic outcomes over long-term follow-up have not been sufficiently investigated. This was a retrospective analysis to evaluate the 10-year oncologic outcomes in T1-3N1 breast cancer after TAS.
Methods
Clinically, we defined TAS as removal of a bunch of ALNs located around SLNs and targeted LNs, but without full exposure of the axillary vein, long thoracic nerve and thoracodorsal nerve.
Between 2008 and 2013, 230 female patients with cT1-3N1 breast cancer underwent breast and axillary surgery (ALND, n = 171; TAS, n = 59) at our institute. After TAS was applied, additional axillary radiotherapy was performed. Various postoperative complications, including postoperative seroma, lymphedema, and 10-year oncological outcomes, were evaluated and compared between the ALND and TAS groups.
Results
Although overall survival during the 10-year follow-up period was better in the TAS group, there was no statistically significant difference in oncologic outcomes, including locoregional recurrence, distant metastasis, and overall survival (p = 0.395, 0.818, and 0.555, respectively). Furthermore, the incidence of lymphedema on the ipsilateral arm was significantly higher in the ALND group (p &lt; 0.001).
Conclusions
The 10-year oncological outcomes of TAS were not inferior to those of conventional ALND in T1-3N1 breast cancers; however, the incidence of lymphedema was significantly higher in the ALND group.
Citation Format: Byeongju Kang, Jeeyeon Lee, Yee Soo Chae, Ho Yong PARK, Jin Hyang Jung. Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-08.