bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-12-05: Gestation and breast cancer in women with mutations in DNA repair genes: Is there any relationship?
Authors: López-herrero lópez María , Estévez Cristina Morales , Triviño Ana Armenta , Contreras Maria Jose , Aguilera Maria Gómez , Alonso Beatriz Rodriguez , Porras Ignacio , de la Haba-Rodríguez Juan , Aguilar Enrique Aranda 
Published: March 2023

Abstract
Introduction: Women carrying mutations in reparative genes frequently ask about the safety of pregnancy or the use of fertility-promoting techniques. The evidence on gestation and breast cancer (BC), specifically in mutated BRCA, provides contradictory results1,3. On the one hand, there are studies that support the protective nature of pregnancy, while others show that gestation is a factor that promotes it1. Likewise, some point to differences in the association according to the type of mutation, BRCA1 or BRCA22.
Objectives: To prove whether there is a relationship between pregnancy and BC in patients with mutations in DNA repair genes and to establish a solid knowledge base for counseling these patients in clinical practice.
Patients and methods: We conducted an analytical, observational and retrospective study of 259 women with mutations in DNA repair genes, whether they had developed cancer or not, with different gestational histories in the Medical Oncology Service. The genes studied were: BRCA1and2, MUTYH, hMSH2, hMSH6,RAD51C,APC,CHECK2,ATM,PALB2,PTEN,BRIP1,ATM+RAD51D,BRCA1+NTHL1,CDKN2A,TP53,NF1,RAD51D.
Results: The proportion of patients who develop cancer in the pregnant group is 46.9%. pregnant women is 46.9%, compared to 37.3% in nulliparous women ((χ²) =1.839, p= 0.171). We observed that the diagnosis of BC occurred before the age of 40 years in 40% of pregnant women, compared to 30% in nulliparous women. Likewise, we observed that from the third pregnancy onwards, the percentage of women suffering from BC is higher, with a peak in the fourth pregnancy (68.8% vs. 31.3%) (p=0.135) and that 51.3% of women whose first pregnancy was before the age of 30 years developed BC, compared to 38.6% in those whose first pregnancy was at a later age (X2=4.16, p=0.041). Finally, we observed that 80% of breast cancers developed after 10 years from the first birth.
Conclusions: Considering our results, we cannot affirm that at present there is an association between gestation and BC in women with mutation in genes involved in DNA repair.
Table: Cross table between cancer (Yes/No) and pregnancy (Yes/No)
Citation Format: María López-herrero lópez, Cristina Morales Estévez, Ana Armenta Triviño, Maria Jose Contreras, Maria Gómez Aguilera, Beatriz Rodriguez Alonso, Ignacio Porras, Juan de la Haba-Rodríguez, Enrique Aranda Aguilar. Gestation and breast cancer in women with mutations in DNA repair genes: Is there any relationship? [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 P5-12-05.
Abstract P5-12-07: Polygenic Risk Score in a cohort of 105 Breast Cancer patients previously tested with a multi gene panel for hereditary cancer
Authors: Tsoulos Nikolaos , Agiannitopoulos Konstantinos , Goga Helen , Troupis Theodoros , Markopoulos Christos 
Published: March 2023

Abstract
AIM: Most patients tested by a 44-gene panel for hereditary cancer (HerediGene), even though they had a strong family history, have a negative result or a finding in a low-risk gene. This creates a question about the risk for these individuals to develop breast cancer. The Polygenic Risk Score is a tool used to identify and calculate the lifetime risk of developing breast cancer and thus we are investigating whether it can be used in our cohort of patients to identify this risk. PATIENTS AND METHODS: Among 111 patients analyzed with a 44-gene hereditary cancer panel, we were able to produce the Polygenic Risk Score for 105 of them. All the patients were diagnosed with breast cancer, and they all had a strong family history. We analyzed the ability of the PRS to identify the risk of the patients in combination with the findings of the 44-gene panel. RESULTS: Overall, 74% of patients with a family history had a negative PRS (with a cut-off of 20%). Among the BRCA positive patients all of them had a positive PRS and among all the high-risk gene positive cases, 70% had a positive PRS. On the other hand, among the low-risk genes and the negative cases 18.5% had a positive PRS. There is a positive correlation between the findings from the NGS panel analysis and the PRS. CONCLUSION: Our analysis shows that PRS is correlated to the findings of the 44-gene NGS panel having the majority of the PRS positive patients carry high risk mutations. In addition to this, in 18.5% of the patients with low-risk findings or negative result from the 44-gene panel, the PRS was positive which can explain the outcome of the patient since breast cancer had developed. This is an indication that the combination of PRS with the findings from the 44-gene panel can identify individuals with a higher risk of developing breast cancer.
Citation Format: Nikolaos Tsoulos, Konstantinos Agiannitopoulos, Helen Goga, Theodoros Troupis, Christos Markopoulos. Polygenic Risk Score in a cohort of 105 Breast Cancer patients previously tested with a multi gene panel for hereditary 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 P5-12-07.
Abstract P6-05-53: “ANDEAN CARAVAN” & “MAUCHIS PLATFORM”: 1st MOBILE CLINIC AND 1st ARTIFICIAL INTELLIGENCE PLATFORM AGAINST CANCER IN PERU
Authors: Rivera Mauricio León , Bocanegra Steffi Katheryne Gonzalez 
Published: March 2023

Abstract
Science, Technology and Society have been related for many years with the goal of providing technological advances for the service of human development. Healthcare has not been immune to this influence and today there are numerous examples that promote the management of various diseases. Therefore, it is important to incorporate this technology into our daily lives, which will allow us to interact quickly and easily with various sectors of Peruvian society, regardless of their level of education or physical location. In this context, Technology and Innovation have become great allies in reinforcing health education and raising awareness of the importance of preventing and reducing the risks caused by cancer. By modifying some lifestyles for "healthy" ones, we would reduce the number of sick people. Knowing that in our country, 11 women die every day from breast and cervical cancer, totally preventable diseases that no one should die from; and that the government is completely overwhelmed in its preventive work, we decided to approach the mining industry. Together, we managed to create a "MOBILE CLINIC", an itinerant bus that will deliver medical care and perform oncological screening tests (Mammography, Ultrasound, Colposcopy and/or Laboratory Tests) to women from vulnerable populations in the communities that are within the area of ​​influence of formal mining in Peru. Similarly, during these meetings all residents will be taught about the use of our Artificial Intelligence platform "MAUCHIS", (www.mauchis.org). Mauchis is the first and only free Platform available 24 hours a day, 365 days a year in Latin America for the prevention of cancer accessible from Whatsapp (+51 1 994003265) and/or Facebook Messenger. This service is free, no payment will be accepted and no institution or company is promoted.
Citation Format: Mauricio León Rivera, Steffi Katheryne Gonzalez Bocanegra. “ANDEAN CARAVAN” & “MAUCHIS PLATFORM”: 1st MOBILE CLINIC AND 1st ARTIFICIAL INTELLIGENCE PLATFORM AGAINST CANCER IN PERU [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 P6-05-53.
Abstract P6-11-01: Scaffold attachment factor B1 modulates cholesterol pathways in triple-negative breast cancer
Authors: Ghidey Meron , Murthy Divya , Yang Sukjin , Ahn Songyeon , Park Jun Hyoung , Kaipparettu Benny 
Published: March 2023

Abstract
Historically known as a tumor suppressor by estrogen receptor (ER) co-repression in breast cancer (BC), the matrix binding protein Scaffold Attachment Factor B1 (SAFB) binds scaffold or matrix attachment region DNA elements (S/MAR DNA) in eukaryotic DNA. SAFB1 plays a role in cellular stress response, DNA repair, differentiation, and apoptosis. SAFB loss in ER-independent BC and pancreatic cancer (PC) patients resulted in poor survival rates, hinting at the role of SAFB1 as a tumor suppressor. To understand the tumor suppressive mechanism of SAFB1, we performed shRNA-mediated knockdown (KD) of SAFB in PC cell lines and triple-negative breast cancer (TNBC) cells, an aggressive subgroup of BC. Analysis of onco-properties showed an increase in clonogenicity potential and cell proliferation in SAFB KDs in both PDACs and TNBCs cells. Further, RNA-Seq analysis of SAFB KDs in the TNBC cell line revealed activation of the mevalonate (MVA) pathway and the resulting cholesterol biosynthesis as the key metabolic change. Both pancreatic ductal adenocarcinoma (PDACs) and TNBC exhibited higher levels of MVA pathway gene expression upon loss of SAFB. Sterol regulatory element binding proteins (SREBP) 1 and 2 dictate cholesterol biosynthesis, and SREBP2 promotes tumor properties via the MVA pathway. Molecular and metabolic analysis of SAFB KD TNBC showed an increase in lipid droplets and SREBP2 maturation. Using Chromatin Immunoprecipitation and quantitative real-time PCR (ChIP-qPCR) in TNBC we demonstrate the direct binding of SAFB to the SREBP2 promoter region. In addition, byproducts of the MVA pathway have been shown to activate YAP/TAZ-dependent tissue homeostasis and tumorigenesis. We also observed increased YAP1 mRNA levels and decreased YAP1 (Ser127) phosphorylation with SAFB loss in TNBC, explaining the aggressive tumorigenicity gained with SAFB loss. Our study thus far suggests SAFB has overt control over the SREBP2-MVA-YAP1 pathway, and loss of SAFB results in an enhanced tumor phenotype.
Citation Format: Meron Ghidey, Divya Murthy, Sukjin Yang, Songyeon Ahn, Jun Hyoung Park, Benny Kaipparettu. Scaffold attachment factor B1 modulates cholesterol pathways 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 P6-11-01.
Abstract P6-12-04: An Inducible Lineage Tracing System for the Identification of Tumor-Initiating Cells
Authors: Souto Eric P. , Lewis Michael T. 
Published: March 2023

Abstract
Background: Metastasis and therapeutic resistance are a major clinical challenge, responsible for the vast majority of cancer deaths. A subpopulation of tumor cells known to have intrinsic resistance to standard therapies and contribute to metastasis function as “cancer stem”, or tumor-initiating, cells (TICs). Enriched populations of TICs are typically identified by markers such as aldehyde dehydrogenase activity, the cell surface marker combination of CD44+/CD24-, or fluorescent reporters for signaling pathways that regulate TIC function such as STAT3. Despite their utility, TIC markers and reporters have limitations. Marker expression can be unstable and there is no established method to lineage trace long-lived TICs or to follow them as they undergo cell state changes. Methods: To augment existing TIC reporters, we developed a two component TAM-inducible, Cre recombinase-dependent, STAT3 signaling-specific lentiviral LT system. The first component is a vector that labels cells with active STAT3 signaling (EGFP+), followed by a self-cleaving peptide and TAM-inducible Cre-recombinase (4M67-EGFP-P2A-CreERT2). The second component is a constitutively expressed dual-color switching Cre-dependent reporter vector (EFS-loxPdsRedloxP-mNeptune2). Addition of TAM drives color switching from dsRed to mNeptune2 via CreERT2 recombination in STAT3 signaling cells. Both lentiviral vectors were constructed using Gateway® Cloning. Sum159 cells were transduced with the LT system and reporter activity was validated both in vitro and in vivo using confocal microscopy and flow cytometry. Four LT cell populations (EGFP+/mNeptune2+, EGFP+/dsRed+, EGFP-/mNeptune2+, and EGFP-/dsRed+) were enriched using fluorescence activated cell sorting, then analyzed by single cell RNA sequencing (scRNA seq). Results: Our results confirm the STAT3 LT reporter identifies STAT3 signaling cells (EGFP+), which can be labelled (mNeptune2+) upon addition of TAM. We conducted a TAM dose response curve to identify the optimal TAM dose for complete and partial labeling of STAT3 signaling cells. scRNA seq uncovered gene expression patterns within the TIC compartment and revealed similarities and differences in gene expression between the TIC compartment and the remaining LT reporter populations. Conclusion: These data demonstrate our LT system is a powerful tool that can be applied to uncover the role of TICs in metastasis and therapeutic resistance, as well as identify genetic vulnerabilities to specifically target TICs.
Citation Format: Eric P. Souto, Michael T. Lewis. An Inducible Lineage Tracing System for the Identification of Tumor-Initiating Cells [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 P6-12-04.
Abstract P6-12-08: Identifying FOXA1 Binding Partners using Proximity Labeling
Authors: Plagens Rosemary N. , Li Shen , Mills Christine A. , Herring Laura , Franco Hector L. 
Published: March 2023

Abstract
Approximately 75% of breast cancers are driven by the estrogen receptor alpha (ER), and despite the advent of endocrine therapy to block ER signaling pathways, a significant portion of women develop resistance to these drugs. The pioneer factor FOXA1 has been shown to facilitate nearly all DNA-binding events of ER in response to estrogen in ER+ breast cancer (ER+BC). Notably, up-regulation of FOXA1 is a hallmark of endocrine-resistant phenotypes and has been shown to reprogram enhancer elements, leading to an altered transcriptome. However, FOXA1 is a critical pioneer factor for multiple nuclear hormone receptors, aside from ER, and is implicated in regulation of important factors such as HER2 and the androgen receptor (AR). With the diverse array of breast cancer molecular subtypes displaying complex interplay between ER, HER2, AR, PR, and other hormone receptors, describing the complete ensemble of FOXA1 binding partners in various contexts, such as endocrine-resistant tumors, is of increasing importance. To define a comprehensive catalog of FOXA1 binding partners under basal conditions, we generated MCF-7 cell lines stably expressing constructs of FOXA1 fused at its N- or C-terminus to the biotin ligase miniTurbo. Using proximity labeling coupled with mass-spectrometry, we have comprehensively cataloged binding partners of FOXA1, including many expected proteins such as ER, AR, MLL3, YAP1, and GATA-3. Moreover, we have discovered more than 150 previously unidentified binding partners of FOXA1, which may exert profound effects on FOXA1 function. Importantly, high hazard ratios and significant dependencies are associated with several of these new binding partners, such as subunits of a previously described histone deacetylase (HDAC) complex containing genetic suppressor element 1 (GSE1) and lysine-specific histone demethylase 1A (KDM1A). Genomic approaches are currently underway to characterize where in the genome FOXA1 is interacting with these novel proteins and to guide future exploration into the physiological significance of these interactions. Integrating biochemical, molecular, and genomic approaches, we have potentially highlighted new mechanisms of FOXA1, which could have significant clinical impact in the future.
Citation Format: Rosemary N. Plagens, Shen Li, Christine A. Mills, Laura Herring, Hector L. Franco. Identifying FOXA1 Binding Partners using Proximity Labeling [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 P6-12-08.
Abstract PD8-05: Effectiveness of Electroacupuncture Versus Auricular Acupuncture in Reducing Pain and Improving Quality of Life in Breast Cancer Survivors with Chronic Musculoskeletal Pain
Authors: Bao Ting , Zhi W. Iris , Baser Raymond , Li Qing , Mao Jun 
Published: March 2023

Abstract
Introduction: Chronic musculoskeletal pain is common and debilitating among breast cancer survivors. Recently, the Personalized Electroacupuncture (EA) versus Auricular Acupuncture (AA) Comparative Effectiveness (PEACE) trial demonstrated that both acupuncture methods reduced pain more than usual care (UC) in cancer survivors. However, the comparative effectiveness between EA and AA among breast cancer survivors is unknown. Here, we report the results of subgroup analysis of breast cancer survivors enrolled in the PEACE trial. Methods: PEACE is a three-arm, parallel, single center randomized trial investigating the effectiveness of EA and AA versus UC for chronic musculoskeletal pain in 360 cancer survivors. Patients in both EA and AA received ten weekly treatments. Patients in UC could receive ten EA treatments after week 12. The primary endpoint was the change in mean Brief Pain Inventory (BPI) pain intensity from baseline to week 12; change from baseline to week 24 and change in quality of life were secondary endpoints. We analyzed the subset of 46% of trial participants with a primary diagnosis of breast cancer. We conducted constrained linear mixed model analyses, which constrained all arms to have a common pre-randomization baseline mean. Model-based mean estimates at weeks 12 and 24 were compared between arms using model contrasts. Results: Among 165 breast cancer survivors, the baseline mean pain severity was 5.35 (95% Confidence Interval [CI]: 5.04, 5.66). At week 12, the BPI pain severity score was 2.69 (2.26. 3.13) in EA, 3.60 (3.17, 4.02) in AA, and 5.06 (4.47, 5.65) in UC. At week 24, the mean BPI pain severity was 2.84 (95% CI: 2.40, 3.28) in EA and 3.67 (95% CI: 3.23, 4.10) in AA. EA reduced pain severity significantly more than AA at both week 12, (-0.90 [-1.45, -0.36], p=0.001) and week 24 (-0.82, [-1.38, -0.27], p=0.004). There were no differences between EA and AA in improvements in PROMIS physical health or mental health component scores, but both EA and AA significantly improved both PROMIS scores at week 12 compared to UC. Mild toxicities were reported, more patients dropped out of the AA arm due to ear pain. Conclusions: EA was more effective than AA at reducing pain severity, but both similarly improved physical and mental health scores. Breast cancer survivors with chronic musculoskeletal pain may consider EA before AA.
Citation Format: Ting Bao, W. Iris Zhi, Raymond Baser, Qing Li, Jun Mao. Effectiveness of Electroacupuncture Versus Auricular Acupuncture in Reducing Pain and Improving Quality of Life in Breast Cancer Survivors with Chronic Musculoskeletal Pain [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 PD8-05.
Abstract WS2-3: Therapy-induced senescence: Friend or foe?
Authors: Stewart Sheila 
Published: March 2023

Abstract
The stromal compartment plays a pivotal role in tumor progression. This is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKa is frequently expressed in tumor cells and surrounding stromal cells and its expression levels correlate with poor prognosis. Using clinically relevant breast cancer metastasis models, we show that orally administered, small-molecule inhibitors of p38MAPKa or its downstream kinase, MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. Further we found that this effect is mediated by inhibition of the p38MAPKa pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, we also found that these inhibitors reduced tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity for cancer patients that drastically impacts their quality of life. Mechanistic studies revealed that p38MAPKa’s ability to limit tumor growth within the bone is dependent on CD4 T cells and macrophages. To determine which cell types within the bone contribute to tumor growth and bone loss, we carried out single cell RNA-sequencing of stromal cells located within the bone metastatic lesion and cells outside the lesion. We found numerous differences that could explain how the stromal compartment contributes to tumor progression and bone loss and how inhibition of p38MAPKa or MK2 contribute. These data underscore the vital role stromal-derived factors play in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss.
Citation Format: Sheila Stewart. Therapy-induced senescence: Friend or foe? [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 WS2-3.
Validation of an Abridged Breast Cancer Risk Prediction Model for the General Population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard 
Published: March 2023

Abstract
Accurate breast cancer risk prediction could improve risk-reduction paradigms if thoughtfully used in clinical practice. Identification of at-risk women is the first step in tailoring risk screening and risk-reduction protocols to women's needs. Using the UK Biobank, we validated a simple risk model to predict breast cancer risk in the general population. Our simple breast cancer risk (BRISK) model integrates a combination of impactful breast cancer-associated risk factors including extended family history and polygenic risk allowing for the removal of moderate factors currently found in comprehensive traditional models. Using two versions of BRISK, differing by 77-single-nucleotide polymorphisms (SNP) versus 313-SNP polygenic risk score integration, we found improved discrimination and risk categorization of both BRISK models compared with one of the most well-known models, the Breast Cancer Risk Assessment Tool (BRCAT). Over a 5-year period, at-risk women classified ≥3% 5-year risk by BRISK had a 1.829 (95% CI = 1.710–1.956) times increased incidence of breast cancer compared with the population, which was higher than the 1.413 (95% CI = 1.217–1.640) times increased incidence for women classified ≥3% by BCRAT.

Prevention Relevance:
In this prospective population-based cohort study, we show the improved performance of a new risk assessment model compared with a gold-standard model (BCRAT). The classification of at-risk women using this new model highlights the opportunity to improve risk stratification and implement existing clinical risk-reduction interventions.