bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-09-03: Real World Data on Neoadjuvant Endocrine Treatment and Ki67 Assessment in ER+/HER2- Breast Cancer. Results from a Single-Institution Prospective Cohort Study
Authors: Marti Covadonga , Frias Laura , Loayza Adolfo , Moreno Elisa , Meléndez Marcos , Sanchez-Mendez Jose Ignacio 
Published: March 2023

Abstract
Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast conserving surgery (BCS) rates and provides an opportunity for assessing in vivo NET effectiveness and studying any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the effectiveness of NET as well as to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness.
Methods: From June 2016 to January 2022, a single-institution cohort of patients treated with NET and further surgery was evaluated. In patients with Ki67≥10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes, as well as surgical management, was gathered.
Results: A total of 168 estrogen receptor positive (ER+)/HER2 negative patients were included. The median age at diagnosis was 69.5 years old (IQR: 16.0). The median treatment duration was 5.0 months (IQR: 4.0). Median maximum size in the surgical sample was 44.0% smaller than pretreatment size measured by ultrasound (p&lt;.0001), showing an inverse linear relationship with treatment duration. Median pretreatment Ki67 expression was 20.0% (IQR: 18.0) and was reduced to 5.0% (IQR: 8.0) after four weeks, and to 2.0% (IQR: 7.25) in the surgical sample (p&lt; 0.0001). Other significant downgrading changes were observed with respect to tumor grade (p&lt; 0.0001) and progesterone receptor (PR) expression (p&lt; 0.0001). BCS was performed on 145 patients (86.3%). One case of pathological complete response was recorded. A larger Ki67 fold-change after four weeks was significantly related to a PEPI score of 0 (p&lt; 0.002). No differences were observed between luminal A- and B-like tumors with regard to fold-change and PEPI score. No treatment abandonment was produced during the study.
Conclusions: In our cohort, NET has proven effective for tumor size and Ki67 downstaging. This results in a higher rate of conservative surgery, aids in therapeutic decision-making, provides prognostic information, and constitutes a safe and well-tolerated approach
Biological changes after NET
Patient and tumor characteristics
Citation Format: Covadonga Marti, Laura Frias, Adolfo Loayza, Elisa Moreno, Marcos Meléndez, Jose Ignacio Sanchez-Mendez. Real World Data on Neoadjuvant Endocrine Treatment and Ki67 Assessment in ER+/HER2- Breast Cancer. Results from a Single-Institution Prospective Cohort Study [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 P5-09-03.
Abstract P6-01-13: Identification of Protein Biomarkers for Early Detection and Stratification of Triple Negative Breast Cancer
Authors: metwali Essraa , Pennington Stephen 
Published: March 2023

Abstract
Breast cancer (BC) is the most frequent malignancy in women worldwide. Breast cancer affects roughly 3,000,000 people worldwide, with triple negative breast cancer (TNBC) accounting for 10-15% of all cases. In comparison to other types of breast cancer, TNBC stands out for its heterogenies disease, poor prognosis and aggressive behaviour. In the early stages of TNBC, neoadjuvant chemotherapy (NAC), which is given to the patient before surgery, has been considered a viable treatment strategy. Pathological complete response (pCR), which has been shown to increase estimates of disease-free (the amount of time following treatment during which there are no signs of malignancy), distant recurrence-free (the cancer has spread to far-off regions of the body) and overall survival, has been linked to NAC in 30% of patients. The objective of this study was to apply mass-spectrometry-based proteomics to serum samples from TNBC patients who have received NAC to identify i) biomarkers that might predict response to NAC, ii) biomarkers that might correlate with the extent of residual disease. These biomarkers will potentially inform treatment decisions such as the escalation/de-escalation of chemotherapy dosage for early TNBC patients. In this study, two proteomic approaches have been used to identify and measure protein candidate biomarkers: un-biased LC-MS/MS and targeted proteomics respectively. The discovery approach led to the identification of 17 unique proteins and 118 unique peptides that were differently expressed. The developing of a multiple reaction monitoring (MRM) assay for biomarker evaluation will be based on the prioritization of the potential signature proteins and other proteins obtained from public resources. Subject to successful evaluation and subsequent validation the candidate biomarkers may be beneficial for identifying TNBC patients who will achieve residual disease after NAC.
Citation Format: Essraa metwali, Stephen Pennington. Identification of Protein Biomarkers for Early Detection and Stratification of Triple Negative 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 P6-01-13.
Abstract P6-05-30: Effects of a 12-Week Exercise Program on Breast Cancer Survivors’ Quality of Life
Authors: Imai Lauren , Baron Kirsten , Toyama Matthew , Pagano Ian , Yamada Paulette , Teranishi-Hashimoto Cheri , Fukui Jami 
Published: March 2023

Abstract
Background: Previous studies have demonstrated that breast cancer survivors commonly experience a decrease in quality of life including an increased risk of depression, insomnia, cancer-related fatigue, and negative body image. Several studies have shown that exercise interventions, such as yoga, Pilates, water aerobics, and strengthening exercises, can improve survivors’ quality of life. We implemented a 12-week exercise program in breast cancer survivors and evaluated body composition and quality of life changes. Here we discuss our findings evaluating 5 quality of life questionnaires.
Methods: We evaluated 22 participants who completed a baseline and post 12-week questionnaire assessments. All participants underwent a 12-week exercise program 3 times/week for 90 minutes/session. We calculated differences in baseline and post 12-week quality of life through 5 questionnaires: Functional Assessment of Cancer Therapy - General (FACT-G), Social Support, Insomnia Severity Index, Brief Fatigue Inventory, and Body Image after Breast Cancer (BIBCQ) and assessed the intervention’s efficacy by comparing the baseline and post 12-week scores using paired t-tests.
Results: The difference between baseline and post 12-week quality of life are presented in Table 1. 7/13 questionnaires showed statistical significance: FACT-G Emotional, FACT-G Functional, Insomnia Severity Index, BIBCQ Vulnerability Scale (VS), BIBCQ Body Stigma Scale (BSS), BIBCQ Limitation Scale (LS), and BIBCQ Body Concern Scale (BCS). Interestingly, 4/6 of the BIBCQ questionnaires showed statistical significance: BIBCQ VS, BIBCQ BSS, BIBCQ LS, and BIBCQ BCS.
Summary: Our study showed improvement in all metrics evaluated in breast cancer survivors who underwent the personalized exercise program. Specifically, multiple questionnaires including body image were improved with exercise which further exemplifies the impact of lifestyle changes on quality of life measures and is an important adjunct to future cancer survivorship studies.
Table 1. Summary of questionnaires with overall significant improvements.
Citation Format: Lauren Imai, Kirsten Baron, Matthew Toyama, Ian Pagano, Paulette Yamada, Cheri Teranishi-Hashimoto, Jami Fukui. Effects of a 12-Week Exercise Program on Breast Cancer Survivors’ Quality of Life [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 P6-05-30.
Abstract P6-05-35: Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama
Authors: Castillo-Fernandez Omar O. , Lim Maria , Montano Lilian 
Published: March 2023

Abstract
Background: 4/6 kinase-dependent cyclin inhibitors have been approved for use in combination with first-line aromatase inhibitors in patients with hormone-sensitive, Her 2neu negative metastatic breast cancer. These agents have significantly improved progression-free survival compared to monotherapy aromatase inhibitors. The purpose of this study was to evaluate the cost-evaluation of each of these new agents (palbociclib, ribociclib, and abemaciclib) in the first line in Panama with the perspective of the National Oncological Institute. Methods: A partition survival analysis was carried out that includes three states (free of progression, progression, and death) with cycles of one month and a time horizon of 7.5 years. The efficacy data were taken from pivotal clinical trials, and the costs were estimated locally. A deterministic and probabilistic sensitivity analysis of the Monte Carlo was performed. Results; According to the base case, the update of each of these strategies involved an increase of USD 355,184 per additional QALY for ribociclib with Letrozole compared to Letrozole; USD 944,148/additional QALY for Palbociclib plus Letrozole; and USD 223,956 for Abemaciclib plus Letrozole, when compared with Letrozole, all above the availability threshold to pay 50,000/QALY. Conclusion: Despite the improvement in progression-free survival, none of the strategies have proved cost-effectiveness in our setting. Price negotiations, cost reduction, and risk-sharing agreements between pharmaceutical companies and payers might improve access to new drugs in countries with limited resources.
Citation Format: Omar O. Castillo-Fernandez, Maria Lim, Lilian Montano. Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama. [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 P6-05-35.
Abstract P6-11-02: Mitochondria-Nuclear Crosstalk Regulates the WNT Pathway in Triple-Negative Breast Cancer
Authors: Yang Sukjin , Park Jun Hyoung , Kim Suna , Ghidey Meron , Kaipparettu Benny 
Published: March 2023

Abstract
Compared to hormone receptor (HR) positive breast cancer (BC), basal or triple-negative BC (TNBC) suffers a poor prognosis caused by a limited understanding of its driver signaling pathways. We used the transmitochondrial cybrid approach to understand the metabolic reprogramming and mitochondria-nuclear crosstalk in metastatic TNBC. In cybrids, mitochondria from cancer and benign cells are compared under a commonly defined nuclear background. Using cybrid-based discovery and its validation in cell lines, patient-derived xenografts, and clinical data, we have previously reported the activation of fatty acid oxidation (FAO) in metastatic TNBC. Recently, we developed a unique gene (DEG) signature by integrating gene expression data from cybrids with different omnibus databases such as TCGA and METABRIC. Our DEG could effectively distinguish the PAM50 subtypes of BC. Further analyses nominated negative regulation of the canonical WNT signaling pathway as one of the major pathways altered by mitochondrial character. The WNT pathway is known to regulate cell signaling, metabolism, epithelial-mesenchymal transition (EMT), and cancer stemness. Cybrids with benign mitochondria showed transcriptional activation of negative WNT regulators, including DKK1, SOST, DAB2, and CAV1. Citrate is a key metabolite from the tricarboxylic acid cycle (TCA cycle) and is an intermediate of many other metabolic pathways. Analysis of TNBC cybrids, cell lines, and BC tissues suggest that in TNBC, citrate levels are increased with the activation of CPT1A, the rate-limiting enzyme of FAO. We confirmed the reduction of the beta-catenin protein in TNBC cells after pharmacological and genetic inhibition of CPT1A and mitochondrial citrate transporter (SLC25A1). We further analyzed the gene set enrichment analysis (GSEA) using gene expression data developed from short and long-term CPT1A inhibited TNBC cells and observed that the FAO alters polycomb repressive complex 2 (PRC2) activity. PRC2 is a critical modulator of the H3K27 methylation pattern as well as pathways related to cancer stemness, including WNT/beta-catenin and Hedgehog (SHH) pathways. These results suggest that the mitochondrial FAO transcriptionally inhibits WNT antagonist genes through repressive histone modification and consequently activates the canonical WNT pathway and cancer stemness. Overall, our current observations provide new insights into the regulation WNT pathway by mitochondria-nuclear crosstalk in TNBC.
Citation Format: Sukjin Yang, Jun Hyoung Park, Suna Kim, Meron Ghidey, Benny Kaipparettu. Mitochondria-Nuclear Crosstalk Regulates the WNT Pathway in Triple-Negative 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 P6-11-02.
Abstract P6-11-04: Novel roles of Inosine Monophosphate Dehydrogenase 2 (IMPDH2) in TNBC doxorubicin resistance
Authors: Fernandes Tatiane da Silva , Bianchi-Smiraglia Anna 
Published: March 2023

Abstract
Triple negative breast cancer (TNBC) is one of the major subtypes of breast cancer, being associated with the lowest survival rate after metastasis occurs. TNBC patients face limited therapeutic options, relying mostly on a combination of chemotherapies (anthracycline, taxanes and cyclophosphamide). However, around 40% of patients treated with chemotherapy relapse due to onset of chemoresistance, contributing to the dismal survival of this aggressive subtype. Therefore, understanding the molecular mechanisms underlying chemoresistance is critical to identify better therapeutic target options. Guanosine triphosphate (GTP) is important for several biological processes, including cell proliferation. We and others have shown that inosine 5’-monophosphate dehydrogenase 2 (IMPDH2), the rate limiting enzyme in the de novo synthesis of GTP, is important in migration and invasion of cancer, including TNBC, however the role it plays in chemoresistance remains to be elucidated. Our preliminary data revealed that IMPDH2 expression levels modulate doxorubicin sensitivity in different TNBC cell lines. Moreover, we have generated MDA-MB-231 cells that are resistant to doxorubicin (referred to as DoxoR), and revealed IMPDH2 to be upregulated in DoxoR cells, at both protein and mRNA levels as well as having higher activity. Consistently, DoxoR cells have ~50% more GTP than their naïve counterpart and, interestingly, are twice more sensitive to treatment with Ribavirin, a well-tolerated FDA approved IMPDH inhibitor, suggesting that Ribavirin could be repurposed for the treatment of chemoresistant TNBC. As expected, RNA sequencing of DoxoR cells revealed increased stemness properties when compared to naïve cells, which we confirmed experimentally in tumor sphere formation assays. Importantly, knockdown of IMPDH2 reverted the ability of DoxoR cells to form bigger tumor spheres, as well as reduced the IC50 of doxorubicin to that of naïve cells. Therefore, our data suggests that increased IMPDH2 and GTP levels in resistant setting could be a potential new vulnerability to be leveraged therapeutically to suppress and/or prevent the growth of chemoresistant lesions.
Citation Format: Tatiane da Silva Fernandes, Anna Bianchi-Smiraglia. Novel roles of Inosine Monophosphate Dehydrogenase 2 (IMPDH2) in TNBC doxorubicin resistance [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 P6-11-04.
Abstract PD6-03: PD6-03 Serum methylmalonic acid concentrations at breast cancer diagnosis strongly correlate with frailty: a retrospective cross-sectional study
Authors: Wu Qi , Hatse Sigrid , Kenis Cindy , Lambrechts Yentl , Punie Kevin , Neven Patrick , Smeets Ann , Laenen Annouschka , Gomes Ana , Fendt Sarah-Maria , Wildiers Hans 
Published: March 2023

Abstract
Introduction: Frailty commonly occurs in older persons, including those with breast cancer diagnoses. Methylmalonic acid (MMA), a metabolite and by-product of propionate metabolism, is known to increase significantly with aging. The relation between MMA concentrations and frailty is currently unknown. Objectives: A cross-sectional study was performed to study the association between baseline serum MMA concentrations and clinical frailty (estimated by G8 screening) in older patients with newly diagnosed breast cancer. Methods: 163 patients ≥70 years old with early-stage breast cancer were included (median age 76y). G8 screening and serum sample collection were performed at breast cancer diagnosis before any therapy was administered. MMA concentrations were measured via liquid chromatography with tandem mass spectrometry (LC-MS-MS). Results: MMA concentrations significantly increased with age (rs=0.3, p&lt;.0001) and serum creatinine levels (rs=0.5, p&lt;.0001) in this older population. The group with an abnormal G8 (≤14/17 = ‘frail’, 48% of patients) had significantly higher MMA levels than the group with normal G8 (&gt;14/17 = ‘fit’, 52%): 250nM vs. 189 nM, respectively (p=.0002). Higher MMA concentrations were independently associated with abnormal G8 (Odds ratio, 1.003, 95%CI 1.0 to 1.006, p=.04) after adjusting for age and serum creatinine levels. Among the different components of G8, MMA concentrations correlated most with weight loss (rs= -0.18, p=.02), mobility (rs= -0.23, p=.002), and polypharmacy (rs= -0.22, p=.005). Conclusion: Elevated serum MMA concentrations at breast cancer diagnosis are significantly associated, not only with age but also independently with clinical frailty in older patients with early-stage breast cancer. MMA may be further evaluated as a biomarker of frailty in older persons with breast cancer.
Citation Format: Qi Wu, Sigrid Hatse, Cindy Kenis, Yentl Lambrechts, Kevin Punie, Patrick Neven, Ann Smeets, Annouschka Laenen, Ana Gomes, Sarah-Maria Fendt, Hans Wildiers. PD6-03 Serum methylmalonic acid concentrations at breast cancer diagnosis strongly correlate with frailty: a retrospective cross-sectional study [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 PD6-03.
Abstract PL2: Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future
Authors: Arteaga Carlos , Francis Prudence 
Published: March 2023

Abstract
Adjuvant endocrine therapy for premenopausal ER+breast cancer had a relatively challenging initial pathway. The earliest trials testing adjuvant ovarian ablation in premenopausal breast cancer were hampered by the lack of ability to test for the relevant target, namely the estrogen receptor (ER). Therefore, trials testing adjuvant ovarian ablation and subsequently ovarian suppression with gonadotropin releasing hormone agonists (GnRHa) were diluted by the inclusion of women with estrogen receptor negative tumors. The subsequent demonstration of the effectiveness of adjuvant chemotherapy, initially with the CMF regimen, diverted some attention away from adjuvant endocrine therapy in premenopausal women, notwithstanding the fact that CMF, initially given for 12 months, resulted in permanent ovarian function suppression in many premenopausal women. Use of adjuvant CMF made it even more challenging to discern the added value of ovarian ablation or suppression. Oral adjuvant endocrine therapy with the selective estrogen receptor modulator tamoxifen became recommended for postmenopausal women, subsequently refined to only those with ER+ breast cancer, but the value of tamoxifen in premenopausal women was initially considered uncertain. Eventually, 5 years of adjuvant tamoxifen became a standard recommendation for premenopausal ER+ early breast cancer, although it took some time for evidence to emerge on the value of adding tamoxifen in women who received chemotherapy. The value of extending adjuvant endocrine therapy beyond 5 years was subsequently studied. More recent randomized premenopausal adjuvant endocrine therapy trials have focused of delineating the value of ovarian function suppression (OFS) added to tamoxifen or to an aromatase inhibitor. There are now a range of options for adjuvant endocrine therapy for premenopausal ER+ breast cancer, and identifying the clinical-pathologic features most appropriate for intensification of adjuvant endocrine therapy can assist with optimizing recommendations for an individual patient.
Citation Format: Carlos Arteaga, Prudence Francis. Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future [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 PL2.
Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer
Authors: Pradat Yoann , Viot Julien , Yurchenko Andrey A. , Gunbin Konstantin , Cerbone Luigi , Deloger Marc , Grisay Guillaume , Verlingue Loic , Scott Véronique , Padioleau Ismael , Panunzi Leonardo , Michiels Stefan , Hollebecque Antoine , Jules-Clément Gérôme , Mezquita Laura , Lainé Antoine , Loriot Yohann , Besse Benjamin , Friboulet Luc , André Fabrice , Cournède Paul-Henry , Gautheret Daniel , Nikolaev Sergey I. 
Published: March 2023

AbstractMetastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers—9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer.Significance:This study highlights the paucity of standard-of-care markers that explain treatment resistance and the promise of investigational and hypothetical markers awaiting further validation. It also demonstrates the utility of molecular profiling in advanced-stage cancers, particularly breast cancer, to improve the survival prediction and assess eligibility to phase I clinical trials.This article is highlighted in the In This Issue feature, p. 1027