bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-02-09: Evaluation of the Automated Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival: TBCRC-005 Prospective Trial
Authors: Visvanathan Kala , Cope Leslie , Fackler Mary Jo , Considine Michael , Carey Lisa , Forero-Torres Andres , Ingle James N. , Lin Nancy U. , Nanda Rita , Storniolo Anna Maria , Tulac Suzana , Wu Natalie C. , Marla Sudhakar , Venkatesan Neesha R. , Wolff Antonio C. , Sukumar Saraswati 
Published: March 2023

Abstract
Purpose: We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we validated the clinical utility of a Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) prototype assay using the GeneXpert® cartridge system for early assessment of disease progression in MBC. Study Design: The 9-marker, LBx-BCM prototype assay was evaluated in TBCRC-005, a prospective biomarker study, using plasma collected at baseline, week 4 and week 8 from 144 MBC patients. Results: At week 4 MBC patients with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months v 6.60 months, p = 0.001) and OS (14.52 months v 22.44 months, p=0.005) compared to those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR = 1.90, 95%CI 1.20-3.01; p =0.006). Change in CM from baseline to week 4 (OR = 4.60, 95%CI 1.77, 11.93; p = 0.002) and high levels of CM at week 4 (OR = 2.78, 95%CI 1.29, 5.99; p = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model (AUC = 0.733) based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment. Conclusion: The easy to perform and automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression early after initiating treatment in women with MBC. Further validation in larger clinical datasets is needed.
Citation Format: Kala Visvanathan, Leslie Cope, Mary Jo Fackler, Michael Considine, Lisa Carey, Andres Forero-Torres, James N. Ingle, Nancy U. Lin, Rita Nanda, Anna Maria Storniolo, Suzana Tulac, Natalie C. Wu, Sudhakar Marla, Neesha R. Venkatesan, Antonio C. Wolff, Saraswati Sukumar. Evaluation of the Automated Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival: TBCRC-005 Prospective Trial [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 P4-02-09.
Abstract P4-03-08: Breast cancer incidence rates in Japan turned into bimodal age distribution in this decade
Authors: Uchida Ken , Ohashi Hitoshi , Nogi Hiroko , Kinoshita Satoki , Nosaka Ryouko , Kamio Makiko 
Published: March 2023

Abstract
BACKGROUND: Japan is the globe’s fastest ageing country: 32.0 % of the female population are 65 or older in 2021. The birth rate was 1.30 children per woman in 2021. Japan’s population has been constantly shrinking since 2011 with aging. The number of breast cancer cases has increased rapidly in the course of low birth rate and aging population. Breast cancer has increased and accounted for the first place of all of cancers in Japanese women. OBJECTIVES; Number of breast cancer has increased recently and accounted for the first place of all of female cancers in Japan. Detailed analytics of the increase and aging of breast cancer are not studied. We elucidate the transformation of Japanese breast cancer by ages at diagnosis over the past decade. MATERIALS: We used the registry data of Japanese Breast Cancer Society and Statistics Bureau of Japan in 2018. Female breast cancer new cases were 59,389 patients in 2008 and 93,858 patients in 2018, respectively. The total female population was 65.441 million in 2008 and 64.911 million in 2018, respectively. 65 years and older women accounted for 23.4% in 2008 and 31.0 % in 2018, respectively. METHODS: We compared incidences and incidence rates of breast cancer by ages in 2008 and 2018, respectively. We used the statistical method of Ameijeiras-Alonso et al for mode assessment. RESULTS; Total number of incidences and incidence rates of breast cancer in 2018 were higher than those in 2008 among all ages. Difference of number of incidences were maximum in age of 60-69 in both years. Difference of incidence rates in both years reached maximum in age of 75-79. Incidence rates in 2008 showed unimodal age distribution with the gentle peak. Incidence rates in 2018 showed bimodal age distribution with two peaks of 45-49 and 65-69. CONCLUSIONS; Incidences and incidence rates of breast cancer increased rapidly among all ages in this decade in Japan. The incidence rates increased most in ages of 75-79 and turned into bimodal age distribution in 2018.
Citation Format: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi, Satoki Kinoshita, Ryouko Nosaka, Makiko Kamio. Breast cancer incidence rates in Japan turned into bimodal age distribution in this decade. [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 P4-03-08.
Abstract P4-03-26: Blood DNA Methylation and Breast Cancer: a Prospective Case-Control Analysis in the Breast Cancer Prospective Family Study Cohort
Authors: Wu HuiChen , Castano Angelica , Liao Yuyan , Santella Regina , Brenner David , Terry Mary Beth , Tycko Benjamin 
Published: March 2023

Abstract
Breast cancer has increased dramatically in young women &lt; 50 years in the US over the past decade. DNA methylation is a type of epigenetic change that plays an important role in cancer etiology by silencing tumor suppressor genes or DNA repair-related genes through hypermethylation or activating oncogenes through hypomethylation. Previous genome-wide association studies have suggested DNA methylation in blood is a potential epigenetic markers of breast cancer risk. In this study, we applied targeted methyl-seq to examine the DNA methylation profile in regulatory sequences of 57 known DNA repair pathway genes, together with 123 other genes, located in immune-related loci and genome-wide association peaks for breast cancer. We used a nested case-control design within the Breast Cancer Prospective Family Study Cohort (FroF-SC) and examined DNA methylation profile in DNA from the blood of breast cancer cases (N=293) and age-matched controls (N=327). In the preliminary data analysis, we observed that the methylation levels in 5 genes were statistically significantly different between cases and controls using Wilcoxon Rank Sum Test (Table 1). Some candidate loci show methylation values spanning a wide range (Std Dev) in both cases and controls, suggesting the presence of genotype-dependent allele-specific methylation (ASM). We then conducted generalized estimating equations (GEE model) adjusting for age at blood draw and calculated the odds ratios (ORs) and 95%CI for the association between methylation levels in the 90th and 10th percentiles of differentially methylated genes (90% vs 10% methylation) and breast cancer risk. The ORs (95% CI) from the GEE models were 1.26 (0.97, 1.63, p=0.08) for CD6, 1.27 (0.85, 1.91, p=0.24) for SDCCAG3, 1.12 (0.85, 1.48, p=0.40) for DCLRE1B, 1.29 (0.88, 1.90, p=0.20) for IP09, and 1.63 (1.08, 2.45, p=0.02) for GNPDA1 (Table 2). The associations were not different by age group. Our preliminary results suggest that DNA methylation measured in blood may be a biomarker of breast cancer susceptibility.
Citation Format: HuiChen Wu, Angelica Castano, Yuyan Liao, Regina Santella, David Brenner, Mary Beth Terry, Benjamin Tycko. Blood DNA Methylation and Breast Cancer: a Prospective Case-Control Analysis in the Breast Cancer Prospective Family Study Cohort [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 P4-03-26.
Abstract P4-03-37: The characteristics of male breast cancer by molecular subtypes: a population-based study
Authors: Wang Min , Liu Deyue , Zhu Li 
Published: March 2023

Abstract
Background: To explore the characteristics of molecular subtype in male breast cancer. Methods: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. Results: A total of 1597 cases were enrolled, including 1373 cases with HR+/HER2- (86%), 182 cases with HR+/HER+ (11.4%), 13 cases with HR-/HER2+ (0.8%) and 29 cases with Triple Negative (1.8%), respectively. There were significant differences in distributions in age, race, grade, tumor size and AJCC stage between the molecular subtypes. The molecular subtypes differed significantly in 5 years overall survival and 5 years cause specific survival, establishing the following sequence with HER2-/HR+ &gt; HER2+/HR+ &gt; HER2+/HR- &gt; Triple negative. According to Cox regression, age&gt;65y, ER negative, PR negative, TN subtype, advanced AJCC stage, larger tumor size, stage T3 and M1 were independent prognostic factors for poorer survival. Conclusion: The prognosis of male breast cancer varied by molecular subtypes. Age, ER and PR, status, stage as well as tumor size were independent prognostic factors.
Citation Format: Min Wang, Deyue Liu, Li Zhu. The characteristics of male breast cancer by molecular subtypes: a population-based 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 P4-03-37.
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

Abstract
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 &gt;=30 kg/m2), overweight (&gt;=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&lt; 0.001) with lower BMI in patients who had MBD type C or D. Patients with higher BMI had lower HDL-Cholesterol (p&lt; 0.001) and higher levels of insulin (p&lt; 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

Abstract
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&lt; 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

Abstract
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

Abstract
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 &gt;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.