bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-03-39: Breast density and Body Mass Index association with breast cancer molecular subtypes in early breast cancer Spanish population
Authors: Calvo Isabel , González Marta , Neria Fernando , Gallegos Isabel , García-Sánchez Lourdes , Pérez Silvia , Estévez Laura G.
Published: March 2023

Obesity is a major health problem and is closely related to the incidence and progression of breast cancer (BC). Likewise, mammogram breast density (MBD) is a risk factor for breast cancer. This study aims to analyze the potential association between BMI (Body Mass Index) and MBD with different molecular subtypes of BC. The interaction with cholesterol, vitamin D, insulin levels, and lifestyle, will also be evaluated. Materials and methods: This is a transversal, descriptive, multicenter study involving women with a recent diagnosis of early BC for one-year duration (November 2019 to October 2020). BMI was classified as obesity (BMI >=30 kg/m2), overweight (>=25 kg/m2), and normal weight (18-25 Kg/m2). American college of radiology was used to classify MBD into 4 categories: A, B, C, and D. Data of weight, height, MBD, molecular subtype (according to 13th St Gallen International Breast Cancer Panel), cholesterol, insulin, vitamin-D, hypertension, diabetes, exercise, and lifestyle were collected at the moment of diagnosis. Results: 162 women with a recent diagnosis of early BC have been successively evaluated in 3 Spanish hospitals. The median age was 52 years, and 49.1% were postmenopausal. Molecular subtypes were: 43% luminal-A, 25% luminal-B, 17% HER2+, and 15% triple-negative. 7% of patients were MBD type A, 17% type B, 55% type C, and 21% type D. 52% were normal weight, 32% overweight, and 16% obese. 48% of women had normal cholesterol levels and 60% normal vitamin D. There was not association between BMI and molecular subtype, however considering menopausal status, BMI was significantly higher in postmenopausal patients with Luminal A subtype (p= 0.011) and HER2+ subtype (p= 0.027). There was no association between MBD and molecular subtype. However, there were significant differences between BMI and MBD (p< 0.001) with lower BMI in patients who had MBD type C or D. Patients with higher BMI had lower HDL-Cholesterol (p< 0.001) and higher levels of insulin (p< 0.001). Conclusion: This study showed a higher BMI in Luminal A and HER2 positive postmenopausal BC patients. Higher BMI was shown in patients with low MBD independently of menopausal status. More studies are needed to understand the role of obesity and molecular subtype of breast cancer.

Citation Format: Isabel Calvo, Marta González, Fernando Neria, Isabel Gallegos, Lourdes García-Sánchez, Silvia Pérez, Laura G. Estévez. Breast density and Body Mass Index association with breast cancer molecular subtypes in early breast cancer Spanish population. [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 P4-03-39.
Abstract P4-07-11: Disparities in the uptake of telemedicine and implications for clinical trial enrollment in breast cancer patients
Authors: Abeloos Camille Hardy , Xiao Julie , Oh Cheongeun , Maisonet Olivier , Gerber Naamit
Published: March 2023

Purpose/Objectives: Since the COVID-19 pandemic, telemedicine has become an attractive alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult telemedicine visit and correlation with clinical trial enrollment. Materials/Methods: We evaluated breast cancer patients seen during the open enrollment of a prospective randomized controlled non inferiority trial evaluating radiation fibrosis with five versus three fractions from 07/13/2020 to 05/13/2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual vs in-person initial consultation and enrolled vs not enrolled patients. All statistical tests were two-sided and the null hypothesis was rejected for p< 0.05. Results: We identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt and radiation at NYU were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial and of those eligible, 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial and of those eligible, 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits. There was no statistically significant difference in patient characteristics between enrolled vs not enrolled patients. Conclusion: Though patient and disease characteristics remained similar between patients undergoing telemedicine and office visits consultations, increased age, unemployment and receipt of chemotherapy were associated with lower usage of telemedicine. Those who underwent in person initial consultation were also more likely to subsequently receive their radiation at our clinic. Further studies are needed to better define underlying reasons for patient selection and impact on care and trial enrollment in order to ensure equal access and benefit from telemedicine, especially in already vulnerable patient populations.

Citation Format: Camille Hardy Abeloos, Julie Xiao, Cheongeun Oh, Olivier Maisonet, Naamit Gerber. Disparities in the uptake of telemedicine and implications for clinical trial enrollment in breast cancer patients [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 P4-07-11.
Abstract P4-08-16: Selective Androgen Receptor Modulators in combination with CDK4/6 inhibitors demonstrate anti-cancer activity in preclinical treatment resistant ER+AR+ breast cancer models
Authors: Freelander Allegra , laven-Law Geraldine , Eshraghi Leila , Geetha Nimmy , Somerville Peta , Pickering Marie , Alexandrou Sarah , Caldon C. Elizabeth , Tilley Wayne D. , Hickey Theresa E. , Lim Elgene
Published: March 2023

Background: The Androgen Receptor (AR) is expressed in up to 90% of all ER+ breast cancers and has been associated with better patient outcome. While androgens were used at a high dose as an anticancer therapy historically, this was discontinued with the advent of Tamoxifen due to virilising effects. Non-steroidal, tissue selective AR modulators (SARMs) represent an attractive alternative, offering a targeted approach to AR activation. Recent compelling pre-clinical data has established that the AR is a tumour suppressor in ER+ breast cancers and that AR activation with a natural androgen or a SARM suppressed ER-driven tumour growth, in preclinical models of endocrine-sensitive and -resistant ER+ breast cancer. Here, we evaluate the efficacy of a SARM (enobosarm) and a natural AR ligand (dihydrotestosterone, DHT) in the context of metastatic, CDK4/6 inhibitor (CDK4/6i) resistant breast cancer. Methods: Enobosarm and palbociclib treatments were evaluated in vitro by colony forming assays using CDK4/6i resistant (MCF7 PalbR) and both endocrine and CDK4/6i resistant (MCF7 cTamPalbR) cell lines. Next, enobosarm or DHT and palbociclib treatment were evaluated in vivo using endocrine and CDK4/6i resistant ER+ patient derived xenograft models (PDX) and cell line xenograft models. IHC, RNA and ChIP sequencing (AR, ER, H3K27ac) were subsequently performed on the harvested tumours. Results: While in vitro and in vivo growth of CDK4/6i resistant preclinical models was inhibited by treatment with a SARM or DHT alone, growth inhibition was more potent and durable in combination with a CDK4/6i. Gene set enrichment analysis of RNA-seq data integrated with ChIP-seq data revealed upregulation of an AR gene signature associated with a better prognosis following treatment with SARM. Co-treatment with a SARM and a CDK4/6i also enhanced AR signalling compared to SARM alone indicating an interaction of the two signalling pathways. Conclusion: Our data indicates that combination treatment with an AR agonist and a CDK4/6i represents a novel therapeutic strategy for CDK4/6i resistant ER+AR+ breast cancers

Citation Format: Allegra Freelander, Geraldine laven-Law, Leila Eshraghi, Nimmy Geetha, Peta Somerville, Marie Pickering, Sarah Alexandrou, C. Elizabeth Caldon, Wayne D. Tilley, Theresa E. Hickey, Elgene Lim. Selective Androgen Receptor Modulators in combination with CDK4/6 inhibitors demonstrate anti-cancer activity in preclinical treatment resistant ER+AR+ breast cancer models. [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 P4-08-16.
Abstract P5-02-34: Single-cell Analysis of KN026 in Combination with KN046 in Treating Patients with Advanced HER2-positive Breast Cancer
Authors: Liu Jieqiong , Liao Jianyou , Tian Zhenluan , Wang Jien , Song Chuangui
Published: March 2023

Background: KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes (two different HER2 epitopes shared by trastuzumab and pertuzumab). KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. Our on-going multi-centered phase II trial (NCT04521179) demonstrated that in advanced HER2-positive breast cancer (HER2+ BC) patients, who have progressed after prior anti-HER2 combinational therapies, the objective response rate (ORR) of this chemo-free therapy of KN026 in combination of KN046 was about 50.0% (SABCS 2021 poster P5-16-04). To explore the underlying mechanism of this regimen, we collected tumor specimens from patients before and after receiving this combinational treatment for single-cell analysis to provide an in-depth description of the tumor immune microenvironment and its correlation with treatment response. Methods: Paired tumor specimens before and after treatment of patients enrolled in the trial were collected for single-cell transcriptome and TCR sequencing. In addition, to reveal the immune cell characteristics of anti-HER2 resistant patients, we compared our data with previously reported single-cell analysis of treatment-naïve HER2+ BC. Results: We obtained 30 specimens from 17 patients, including 17 of pre-treatment and 13 of post-treatment. TCR expansion did not correlate with clinical efficacy. In-depth analysis of subpopulations revealed that compared to treatment-naive HER2+ BC, these enrolled prior anti-HER2-resistant patients had an additional population of T cells subpopulation characterized by CD4-low and CD8-low in their baseline tumor tissues, and the proportion of this subpopulation was significantly decreased after KN046 plus KN026 treatment in responding patients. Moreover, we found that patients with baseline CD8+ T/naïve T >1 tended to benefit more from this regimen. Conclusion: We identified a subpopulation of CD4-low and CD8-low T cells that may be associated with anti-HER2 resistance. And decreased of this subpopulation of T cells was associated with better ORR of KN046 in combination with KN026 treatment in heavily pretreated advanced HER2+ BC. Baseline CD8+ T/naïve T ratio in tumor is expected to be a predictor of ORR as well.

Citation Format: Jieqiong Liu, Jianyou Liao, Zhenluan Tian, Jien Wang, Chuangui Song. Single-cell Analysis of KN026 in Combination with KN046 in Treating Patients with Advanced HER2-positive 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 P5-02-34.
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

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

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

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

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

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

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

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

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

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.
A Paternal "Balanced" Chromosome 2 and 4 Translocation with Chromosome 21q Insertion Leading to Duplication of 2q22.1q24.1 in Two Siblings
Authors: Gökoğlu Mustafa , Yürür Kutlay Nüket , Altıner Şule
Published: March 2023

Complex chromosomal rearrangements (CCRs) have been described as alterations between two or more chromosomes with at least 3 breakpoints. CCRs can cause copy number variations (CNVs) resulting in developmental disorders, multiple congenital anomalies, and recurrent miscarriages. Developmental disorders are an important health problem affecting 1–3% of children. The underlying etiology can be explained by CNV analysis in 10–20% of children who have unexplained intellectual disability, developmental delay, and congenital anomalies. Here we report two siblings who were referred to us with intellectual disability, neurodevelopmental delay, happy demeanor, and craniofacial dysmorphism due to chromosome 2q22.1q24.1 duplication. Segregation analysis showed that the duplication originated from meiotic segregation of a paternal translocation between chromosomes 2 and 4 with chromosome 21q insertion. Considering that infertility is seen in many male individuals with CCRs, it is remarkable that the father does not have any fertility problems. Gain of chromosome 2q22.1q24.1 was responsible for the phenotype due to its size and presence of a gene with a probability of being triplosensitive. We corroborate the assumption that the major gene responsible for the phenotype in the 2q23.1 region is methyl-CpG-binding domain 5, MBD5.
Relationship between Cognitive Decline and Daily Life Gait among Elderly People Living in the Community: A Preliminary Report
Authors: Yamagami Tetsuya , Yagi Motoi , Tanaka Shigeya , Anzai Saori , Ueda Takuya , Omori Yoshitsugu , Tanaka Chika , Shiba Yoshitaka
Published: March 2023

Introduction: Early detection and intervention are important to prevent dementia. Gait parameters have been recognized as a potentially easy screening tool for mild cognitive impairment (MCI); however, differences in gait parameters between cognitive healthy individuals (CHI) and MCI are small. Daily life gait change may be used to detect cognitive decline earlier. In the present study, we aimed to clarify the relationship between cognitive decline and daily life gait. Methods: We performed 5-Cog function tests and daily life and laboratory-based gait assessments on 155 community-dwelling elderly people (75.5 ± 5.4 years old). Daily life gait was measured for 6 days using an iPod-touch with an accelerometer. Laboratory-based 10-m gait (fast pace) was measured using an electronic portable walkway. Results: The subjects consisted of 98 CHI (63.2%) and 57 cognitive decline individuals (CDI; 36.8%). Daily life maximum gait velocity in the CDI group (113.7 [97.0–128.5] cm/s) was significantly slower than that in the CHI group (121.2 [105.8–134.3] cm/s) (p = 0.032). In the laboratory-based gait, the stride length variability in the CDI group (2.6 [1.8–4.1]) was significantly higher than that in the CHI group (1.8 [1.2–2.7]) (p < 0.001). The maximum gait velocity in daily life gait was weakly but significantly correlated with stride length variability in laboratory-based gait (ρ = −0.260, p = 0.001). Conclusion: We found an association between cognitive decline and slower daily life gait velocity among community-dwelling elderly people.
Development of an in vitro Functional Assay to Evaluate the Occlusive Properties of Moisturizers on Dry Skin
Authors: Hong Soonjin , Maitra Prithwiraj , Nguyen Audrey , Kadoya Kuniko , Mehta Rahul C.
Published: March 2023

Introduction: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. Methods: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. Results: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products. Conclusion: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions.
Survival of mushrooms and termites upon pesticide exposure in the cocoa agro-ecosystem
Authors:   Cocoa Research Institute of Ghana, Entomology Division, Kumi Eric , Avicor Silas ,   Cocoa Research Institute of Ghana, Entomology Division, Bukari Yahaya ,   Cocoa Research Institute of Ghana, Plant Pathology Division, Attah Ishmael ,   Cocoa Research Institute of Ghana, Plant Pathology Division, Agyare Solomon ,   Cocoa Research Institute of Ghana, Plant Pathology Division, Yebaoah Mabel ,   Cocoa Research Institute of Ghana, Plant Pathology Division, Kwagyan Michael ,   University of Ghana Legon
Published: March 2023

Pesticides have become integral parts of cocoa cultivation for the management of insect pests and fungal pathogens which cause significant damage to the crop. However, continuous pesticides usage in the cocoa agro-ecosystem is of concern due to perceived adverse effects on non-target organisms. In this study, mushrooms and associated termites were used to elucidate the possible effect of insecticides and fungicides on non-target organisms in the cocoa agro-ecosystem. Vegetative phase of Pleurotus sajor-caju (Oyster mushroom), Volvariella volvacea (Paddy straw mushroom), Termitomyces globulus and Termitomyces robustus (Termite mushrooms) were subjected to concentrations of commercially formulated fungicides (metalaxyl 12 % + copper (I) oxide 60 % and cupric hydroxide 77 %) and insecticides (imidacloprid 20 % and bifenthrin 2.7 %) to observe their growth rates on Potato Dextrose Agar (PDA) medium. Worker termites, Macrotermes bellicosus, were also exposed to the pesticides in Petri dishes for 24 h to observe their mortality. The manufacturer’s recommended concentration of 245 ppm for bifenthrin completely inhibited mycelial growth of all the mushrooms and caused 100% mortality of termites. At 0.0245 ppm, the insecticide caused 60% mortality of termites, but it had no inhibitory effect on the mushrooms. Except P. sajor-caju, mycelial growth of all the other mushrooms were completely inhibited by metalaxyl + copper (I) oxide at the manufacturer’s recommended concentration of 2400 ppm. However, mycelial growth rate of the mushrooms at 0.24 ppm of the fungicide was similar to the control plates. This suggests that mushrooms could survive in the cocoa agro-ecosystem amidst pesticides at lower concentrations in cocoa soils.
Effect of Extraction Solvent and Harvest Time on Recovery of Bioactive Com-pounds, Antioxidant and Cancer Cell Growth Inhibition Activities of Korean Ca-mellia mistletoe
Authors:   Toxicology Laboratory, Department of Biotechnology (Biomaterials), College of Applied Life Science, Jeju Na-tional University, Jeju, 63243, Republic of Korea, Kim Min
Published: March 2023

This study aimed to determine the phytochemical profiles,in vitroantioxidant and antiproliferative properties of KoreanCamellia mistletoe(Korthalsella japon-ica(Thunb.) Engl.) depending on the harvest time (August and November) and sol-vent (100% methanol, 70% ethanol, and hot water). TheCamellia japonicaL. mistle-toe extracts were analyzed for total phenol, flavonoid, carotenoid, and L-ascorbic acid contents and antioxidant properties such as scavenging capacities (1,1-diphenyl-2-pic-rylhydrazyl (DPPH) and NO•),ferrous ion chelating and reducing power. Concur-rently, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as-say was used to assess the antiproliferative properties against human cancer cell lines; MCF (human breast cancer cells), HeLa (human cervical cancer cells), A375 (human malignant melanoma cells), HCT116 (human colon cancer cells), HepG2 (human liver cancer cells) and A549 (human non-small cell lung adenocarcinoma cells). The results showed that extraction solvent and harvest time had significant impacts on antioxidant and anticancer activities and selectivity for free phenolic compounds inCamellia ja-ponicaL. mistletoe. Among all the tested extracts, the highest amounts of total phe-nolic and total flavonoids content were found in ethanol extracts ofCamellia japon-icaL. mistletoe harvested in November, while the methanol extracts ofCamellia ja-ponicaL. mistletoe collected in August showed the highest contents of total carote-noids and L-ascorbic acidscompared to the other tested extracts. Additionally, the highest NO•radical scavenging activity was found in ethanol extracts, whereas the strongest DPPH radical scavenging activity was found in methanol extracts ofCamel-lia japonicaL. mistletoe harvested in November. Furthermore, methanol extracts showed much higher antiproliferative activity against all human cancer cells than eth-anol extracts ofCamellia japonicaL. mistletoe harvested in November. In conclusion, the antioxidant and anticancer properties ofCamellia japonicaL. mistletoe showed significant dependence on the extraction solvent type and harvest time. With optimum harvest time and extraction solvent, they boast a wide range of promising medical, pharmaceutical, and food applications
Effect of microbial inoculant on the oviposition and completion of life cycle of Chrysomya megacephala(Fabricius) and Chrysomya rufifacies(Macquart) infest-ing rabbit carcasses
Authors:   Department of Chemistry, Faculty of Science, University Teknologi Malaysia, 81310 Skudai, Johor, Mahat Naji , Omar Nur ,   Department of Chemistry, Faculty of Science, University Teknologi Malaysia, 81310 Skudai, Johor, Chin Heo ,   Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh, Selangor, Malaysia, Kamaluddin Mohammad ,   Centre for Research in Psychology and Human Well-Being, Faculty of Social Sciences and Humanities, Department of Universiti Kebangsaan Malaysia, 43600, Malaysia, Muda Nor ,   Department of Chemistry, Faculty of Science, University Teknologi Malaysia, 81310 Skudai, Johor
Published: March 2023

This research was conducted to assess the influence of microbial inoculant (EM.1®) on the initial oviposition and developmental pattern of two prevalent necrophagous flies (Chrysomya megacephala and Chrysomya rufifacies) in Malaysia. Nine rabbit carcasses were equally divided into control and two treated groups. The control carcasses were sprayed with deionized water (about 100 mL), whereas the two other treated groups were individually sprayed with two concentrations of EM.1® at 1:500 and 1:100, respectively. Results revealed that the single application of EM.1® on both treated carcasses did not statistically impede oviposition by both necrophagous species, as well as their subsequent developmental patterns (P > 0.05) when compared with that of controls. Therefore, estimating the minimum post-mortem interval (mPMI) using empirical baseline data for the control animal model would remain appropriate for estimating mPMI in cases involving carcasses with a single application of EM.1®