bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-01-01: Unicentric experience with icdk4/6 in metastatic breast cancer
Authors: Henao Fernando , Fernández Esteban Nogales , Ortega Lourdes Sevilla , Salas Ruben De Toro , Carrión Natalia Palazón , de la Gala Maria del Carmen Álamo , Mejías Alberto Sanchez-Camacho , Leon Maria Luisa Sanchez , de la Cruz-Merino Luis 
Published: March 2023

Abstract
Currently, the standard of care for luminal metastatic breast cancer is the combination of cyclin inhibitors with hormone therapy. Palbociclib and Ribociclib have been approved for marketing since 2017 and Abemaciclib since 2019 in Spain. In our center we have experience with the three cdk 4/6 inhibitors in different lines of treatment and patient profiles. We gather in the present work the unicentric experience with the three icdk 4/6. We have collected a total of 152 patients treated with the different cyclin inhibitors, achieving median PFS of 32.1 months for Palbociclib, 28.6 months for Ribociclib and 18.4 months for Abemaciclib. Overall survival data is still immature. The context of the patient and the disease has a significant impact on the results, as well as the line of treatment used. The toxicity profile of the three drugs does not differ from what the registry trials describe, with neutropenia being the most common side effect. We also describe dose reductions produced by the three icdk4/6. Conclusions: This is a real-life study with experience in a single center with the three icdk4/6 currently marketed with a cohort of more than 150 patients. We present data that conform to what was reported by the clinical trials PALOMA, MONALEESA and MONARCH. The data will be updated on the date of the congress for its presentation.
Citation Format: Fernando Henao, Esteban Nogales Fernández, Lourdes Sevilla Ortega, Ruben De Toro Salas, Natalia Palazón Carrión, Maria del Carmen Álamo de la Gala, Alberto Sanchez-Camacho Mejías, Maria Luisa Sanchez Leon, Luis de la Cruz-Merino. Unicentric experience with icdk4/6 in metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-01.
Abstract P3-01-10: Going beyond the median: Estimating survival times for patients with hormone receptor positive, metastatic breast cancer commencing endocrine therapy
Authors: Parsonson Andrew O. , Sarkar Sunit , Brown Lauren , Kiely Belinda , Vasista Anuradha 
Published: March 2023

Abstract
Background: Oncologists are often asked to provide information about expected survival times for patients with metastatic breast cancer (MBC). We have previously demonstrated that using estimates of best-case, typical and worst-case scenarios for survival to explain life expectancy conveys more meaning and hope than simply providing single point estimates of the median overall survival (OS). Our aim was to assess whether using simple multiples of the median could accurately assess scenarios for survival for patients with estrogen receptor (ER) positive, MBC starting endocrine therapy (ET) using simple multiples of the median. Methods: We systematically searched for randomised trials of ET for ER positive MBC. We then recorded the following percentiles (representative scenarios) from the OS curve of each trial using UN-SCAN-IT® graph digitising software: 90th (worst-case), 75th (lower-typical), 50th (median) 25th (upper-typical), and 10th (best-case). We assessed the accuracy of estimating these percentiles for each OS curve by multiplying the median OS by four simple multiples: 0.25 (to estimate the 90th percentile), 0.5 (75th), 2 (25th) and 3 (10th). Estimates were deemed accurate if within 0.75 -1.33 times the actual value. Results: We identified 24 trials with 10,068 patients. The median OS (interquartile range [IQR]) was: 61.3 months (53.4-64.8) for first-line ET with cyclin-dependant kinase 4/6 inhibitors (CDK4/6i) (4 treatment groups); 42.6 months (40.9-50.4) for first-line ET alone (23 treatment groups) and 29.2 months (24.8-33.4) for subsequent line ET (21 treatment groups). The median OS (IQR) for each scenario for first-line ET with CDK4/6i was: worst-case 17.4 months (13.8-20.7); lower-typical 32.5 months (29.3-34.9); upper-typical and best-case percentiles were not available. Simple multiples of the median OS accurately estimated the 90th percentile in 79%; 75th percentile in 93%; and 25th percentile in 76% of curves. The 10th percentile was only available for four OS curves and could not be accurately assessed. Conclusion: Using simple multiples of the median OS to estimate and explain survival times to patients with MBC starting ET, is accurate and meaningful. Longer follow-up of trials is required to help clinician’s estimate the best-case scenario for these patients.
Citation Format: Andrew O. Parsonson, Sunit Sarkar, Lauren Brown, Belinda Kiely, Anuradha Vasista. Going beyond the median: Estimating survival times for patients with hormone receptor positive, metastatic breast cancer commencing endocrine therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-10.
Abstract P3-03-23: Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis
Authors: Jordt Nanna , Kjærgaard Kasper , Borgquist Signe , Thomsen Reimar W. , Cronin-Fenton Deirdre 
Published: March 2023

Abstract
Introduction Due to improvements in breast cancer (BC) diagnostics and treatment, the population of BC survivors is growing. BC treatments may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). It is therefore important to investigate the risk of T2D in patients with BC in general and according to type of adjuvant BC treatment. Objectives To conduct a systematic review and meta-analysis investigating the association between early BC and the risk of subsequent T2D diagnosis. A secondary aim was to examine this association according to type of adjuvant BC treatment––chemotherapy and endocrine therapy (ET). Methods We searched PubMed and Embase using variations of the search terms breast cancer (population), ET, tamoxifen, aromatase inhibitors (AIs) and chemotherapy (exposures), and diabetes mellitus (outcome). Two authors screened papers for eligibility by title and abstract using Covidence and reviewed full texts of eligible papers. Guided by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, study data were extracted. Using random-effects models, we calculated relative risks (RRs) and associated 95% confidence intervals (CIs) for the association between BC, adjuvant BC treatment (ET overall, tamoxifen, and AIs), and subsequent T2D. We used funnel plots to assess publication bias in the analyses. Results Among 16 eligible studies, 11 reported on T2D risk after BC, chemotherapy, or ET; five studies investigated more than one association. Compared with patients without BC, those with BC had elevated risk of T2D overall (RR=1.27, 95%CI=1.15-1.41), particularly those who received any ET (RR=1.23, 95% CI=1.16-1.32). Among BC patients only, risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (RR=1.19, 95% CI=1.13-1.25). Due to few studies, analyses investigating T2D risk after treatment with AIs and chemotherapy were inconclusive. Conclusion Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the impact of ET overall, AIs and chemotherapy on the incidence of T2D in patients with early BC. Funding This project was funded from the following source: The Novo Nordisk Foundation (NNF20OC0065928)
Citation Format: Nanna Jordt, Kasper Kjærgaard, Signe Borgquist, Reimar W. Thomsen, Deirdre Cronin-Fenton. Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-23.
Abstract P3-05-11: Breast cancer characteristics in premenopausal women by contraception method
Authors: De Maeyer Inés , Borowski Eline , Van Baelen Karen , Laenen Annouschka , Nevelsteen Ines , Wildiers Hans , Han Sileny , Smeets Ann , Baert Thaïs , Punie Kevin , Neven Patrick 
Published: March 2023

Abstract
INTRODUCTION: Our knowledge regarding the levonorgestrel intra-uterine device (LNG-IUD) and breast cancer (BC) risk is limited. As the LNG-IUD is a widely used contraception method, we here explored receptor expression in BC, in women &lt; 56 years, by having a LNG-IUD at diagnosis. We aim to validate the findings of a previous cohort treated in the University Hospitals Leuven, where we observed proportionally more progesterone receptor (PR), lower human epidermal growth factor receptor 2 (HER2) expression and more ER+PR+HER2- subtypes in LNG-IUD users compared to non-LNG-IUD users. MATERIALS AND METHODS: We conducted a retrospective observational monocentric study from 2015 until 2020. We included patients &lt; 56 years consulting the University Hospitals Leuven for primary invasive BC, who were treated with primary breast surgery or neoadjuvant therapy. We compared patient and tumor characteristics, especially receptor subtypes in LNG-IUD users at diagnosis with non- LNG-IUD users. Group comparisons with regards to receptor subtypes were performed by the Chi-square test, all tests were evaluated at a two-sided 5% significance level. RESULTS: Of the 1347 patients with BC included in this study, 272 had a LNG-IUD at diagnosis. The LNG-IUD users were more likely ER (85.29% vs 77.77%, p=0.006) and PR positive (80.88% vs 70.95%, p&lt; 0.001) compared to the control group. Additionally, we observed more ER+PR+HER2- (68.75% vs 58.62%, p=0.002) and fewer ER-PR- HER2- (10.29% vs 15.66%, p=0.025) subtypes when comparing with the control group. CONCLUSION: This internal validation study confirmed invasive BC, diagnosed in women under age 56, to be more likely PR+ and ER+PR+HER2- if they used a LNG- IUD at BC diagnosis when compared to non-LNG-IUD users.
Citation Format: Inés De Maeyer, Eline Borowski, Karen Van Baelen, Annouschka Laenen, Ines Nevelsteen, Hans Wildiers, Sileny Han, Ann Smeets, Thaïs Baert, Kevin Punie, Patrick Neven. Breast cancer characteristics in premenopausal women by contraception method [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-11.
Abstract P3-05-37: Influence of Clinical Heterogeneity on Pregnancy Associated Breast Cancer survival: Systematic Review with Metanalysis
Authors: ANTONINI MARCELO , TAIS BARROS T. , REAL JULIANA M. , LOPES REGINALDO G. COELHO , FERRARO ODAIR , MATTAR ANDRE , OKUMURA LUCAS 
Published: March 2023

Abstract
Objective: Pregnancy-associated breast cancer (PABC) is defined as diagnosed during pregnancy or within one year of childbirth, in which current evidence associates with poor prognosis, without showing what clinical characteristics could impact in survival. We aim to explore the impact of heterogeneity in risks on death and disease relapse, suggesting clinical characteristics that might improve PABC clinical outcomes.
Methods: Medline, Embase, Cochrane, Lilacs and congress abstracts published since 2000 were used as data sources. Two reviewers independently selected manuscripts and extracted data and a third reviewer solved discrepancies. The primary outcome was overall survival (death), and secondary outcome was disease-free survival (death or relapse). Summarized hazard ratios were recalculated based on reported data. All metaanalyses used a random-effects model and heterogeneity was reported using the I2 method.
Results: A total of 7143 studies were identified and 30 studies were included for metaanalyses. PABC is associated with a 96% (HR=1.96, 95%CI 1.58;2.35) higher risk of death and an additional 82% (HR=1.82, 95%CI 1.45;2.20) risk of death or disease relapse in comparison to a population of non-PABC or nulliparous BC. Through sensitivity analyses, we identified that clinical outcomes was impacted, possibly due to Ki-67 levels, poorly differentiated tumors, and triple negative breast cancer (TNBC) frequency in the study.
Conclusions: PABC is correlated with poorer prognosis, suggesting that besides early diagnosis, Ki-67 levels, poorly differentiated tumors and TNBC might be relevant sources of inconsistency. So, such clinical sources of heterogeneity should be better investigated regarding the potential to evaluate alternative therapeutic strategies.
PABC deaths compared to non-PABC population, represented as hazard ratio
PABC deaths or disease relapse compared to non-PABC population, represented as hazard ratio
Citation Format: MARCELO ANTONINI, BARROS T. TAIS, JULIANA M. REAL, REGINALDO G. COELHO LOPES, ODAIR FERRARO, ANDRE MATTAR, LUCAS OKUMURA. Influence of Clinical Heterogeneity on Pregnancy Associated Breast Cancer survival: Systematic Review with Metanalysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-37.
Abstract P3-05-50: Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer
Authors: Zhang Hongfei , Yu Xiafei , Yang Junzhe , Liu Xiaoan , Zhu Yanhui 
Published: March 2023

Abstract
Background: Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer. Methods: Pearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Ultimately, a nomogram based on the risk score and several significant clinicopathologic features was established. Results: The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Conclusions: The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies.
Citation Format: Hongfei Zhang, Xiafei Yu, Junzhe Yang, Xiaoan Liu, Yanhui Zhu. Comprehensive Analysis of Pyroptotic Gene Prognostic Signatures Associated with Tumor Immune Microenvironment and Genomic Mutation in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-50.
Abstract P3-05-56: The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis
Authors: Ahn Jee Hyun , Lee Suk Jun , Go Jieon , Park Hyung Seok , Kim Jee Ye , Kim Seung Il , Park Byeong Woo , Park Seho 
Published: March 2023

Abstract
Introduction: More than half of the results of axillary lymph node dissection followed by metastasis in sentinel lymph node(SLN) biopsy are negative. For deescalating axillary surgery, it is necessary to predict the non-SLN metastasis state, where metastasis was confirmed in the SLN biopsy. Method: Breast cancer patients with T1 and T2 stage were retrospectively reviewed from January 2008 to December 2016. A total of 818 patients underwent surgery as the primary treatment and the result of SLN biopsy was positive for metastasis. Patients who skipped SLN biopsy procedure and were proven metastatic axillary lymph nodes by needle-aspiration biopsy (NAB) were excluded. SLN was defined as lymph nodes detected by the dual method with hot-uptake by radioisotope and dyed by blue dye, or lymph nodes with palpable or suspected metastatic findings during SLN biopsy. Clinicopathological factors including and extra-nodal invasiveness were analyzed. Result: The median follow-up period was 73 months. Non-SLN metastasis was significantly seen in patients with older than 50 years, positive node metastases by preoperative NAB, high T stage, and extra-nodal invasion. In subgroup analysis, patients who underwent total mastectomy had the similar patterns of the increased risk of having non-SLN. Poor overall survival was observed in the patients with the presence of non-SLN metastasis. Conclusion: We confirmed predictive factors with a high probability of non-SLN metastasis. Axillary lymph node dissection cannot be overlooked in the patients proven the metastatic result of preoperative NAB.
Citation Format: Jee Hyun Ahn, Suk Jun Lee, Jieon Go, Hyung Seok Park, Jee Ye Kim, Seung Il Kim, Byeong Woo Park, Seho Park. The clinical impact of preoperatively needle-aspiration biopsy for axillary lymph nodes in T1-T2 breast cancer patients with axillary lymph node metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-56.
Abstract P3-07-02: Anti-tumor efficacy of GMF-1A3, an MMAE-based antibody drug conjugate targeting cell surface cleaved Amphiregulin in breast cancer
Authors: Lofgren Kristopher , Sreekumar Sreeja , Reker Nicolette , Ernzen Kyle , Kenny Paraic A. 
Published: March 2023

Abstract
The Epidermal Growth Factor Receptor ligand, Amphiregulin, is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. Amphiregulin is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is subsequently internalized. Here, we describe the development of an antibody drug conjugate, GMF-1A3-MMAE, targeting an AREG neo-epitope revealed following ADAM17-mediated cleavage. The antibody does not interact with uncleaved Amphiregulin, providing a novel means of targeting cells with high rates of Amphiregulin shedding. Using fluorescent dye conjugation, we demonstrated that the antibody is internalized by cancer cells in a manner dependent on the presence of cell surface cleaved Amphiregulin. Antibodies conjugated with monomethyl auristatin E (MMAE) were cytotoxic in vitro and induced rapid regression of established breast tumor xenografts in immunocompromised mice. We further demonstrate that these antibodies recognize the Amphiregulin neo-epitope in formalin fixed paraffin embedded tumor tissue, suggesting their utility as a companion diagnostic for patient selection. A pan-cancer tissue microarray analysis indicates that the target is commonly detected (&gt; 50% of cases) in breast, prostate, liver and lung cancer.
Citation Format: Kristopher Lofgren, Sreeja Sreekumar, Nicolette Reker, Kyle Ernzen, Paraic A. Kenny. Anti-tumor efficacy of GMF-1A3, an MMAE-based antibody drug conjugate targeting cell surface cleaved Amphiregulin in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-02.
Abstract P3-07-17: Nanosecond Electric Pulses Modify Breast Tumor Microenvironment to Promote Antitumor Immunity
Authors: Yang Lifang , Nanajian Anthony , Beebe Stephen , Guo Siqi 
Published: March 2023

Abstract
Cancer immunotherapy has had a significant impact on the management of many types of solid tumors. While some patients respond favorably to it, a significant number of patients do not respond or initially respond but develop resistance later, highlighting an unmet need to improve the effectiveness of this treatment. Cancers with intrinsic resistance include breast cancer, not only respond poorly to single agent immunotherapy, but also often show no durable response. Tumor microenvironment (TME) plays a critical role in both pre-existing and acquired immune resistance which is responsible for the low immunogenicity of cancers. We previously reported that an electrical engineering technology generating nanosecond length electric pulses (nsEP) can greatly enhance the immunogenicity of poorly immunogenic cancers including 4T1 breast and Pan02 pancreatic in animal models. To understand how nsEPs overcome predominant immunosuppression in the TME to induce a strong immune response, we further investigated the effects of nsEPs on the breast TME by performing transcriptomic and immune profiling of 4T1 breast cancer cells treated with nsEP. RNAseq data and cell death signaling results demonstrated that nsEPs induced regulated necrotic cell death rather than apoptosis. NsEPs-treated cancer cells greatly decreased angiogenic factors and multiple chemoattracts for myeloid-derived suppressor cells (MDSCs) and macrophages. On the other hand, nsEP-treated cancer cells significantly upregulated chemoattracts for T lymphocytes and a number of proinflammatory/immunostimulatory cytokines. Flow cytometry analysis showed that the dynamic changes of TME following nsEP treatment included: (1) the significant reduction of immunosuppressive cells (MDSCs, Tregs and TAMs); (2) the preservation of cytotoxic CD8+ T cells and conventional CD4+ T cells; and (3) a persistent elevation in cytotoxic cells vs Treg ratio and tissue resident memory CD8+ T cells. Taken together, our results suggest nsEP is a TME modifier that can potentially overturn the immunosuppressive hurdle in the TME to promote antitumor immunity.
Citation Format: Lifang Yang, Anthony Nanajian, Stephen Beebe, Siqi Guo. Nanosecond Electric Pulses Modify Breast Tumor Microenvironment to Promote Antitumor Immunity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-17.