bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO3-28-08: Triple Hormone Receptor Signatures as Novel Prognostic Markers in Breast Cancer
Authors: Omar Mohamed , Harrell Chuck , Tamimi Rulla , Marchionni Luigi , Ince Tan 
Published: May 2024

Abstract
Background Tumor phenotype across various cancers, including breast cancer, is predominantly shaped by a synergy between genomic alterations and the cell-of-origin from which the tumor emerges. These elements collectively influence crucial aspects like tumor aggressiveness, treatment response, and patient prognosis. While existing research highlights that the cell-of-origin often leaves a lasting imprint on the molecular architecture of tumors, leveraging this information for actionable clinical insights has proven challenging. Specifically, in the realm of breast cancer, utilizing cellular ancestry signatures could be a key factor in tailoring effective therapeutic strategies and improving patient outcomes. Methods In this study, we developed a unique signature anchored in the expression levels of triple hormone receptors (THR)—namely androgen (AR), estrogen (ER), and vitamin D (VDR)—in normal breast cells. Building on this, we formulated two distinct mRNA markers, THR-50 and THR-70, aimed at categorizing breast tumors based on their THR expression profiles. These markers were rigorously validated across 65 independent breast cancer studies, involving a total of 6,679 patients, utilizing Kaplan-Meier survival curves, Cox proportional hazards models, and unsupervised clustering analyses. Results Our findings indicate that both THR-50 and THR-70 are robustly associated with overall survival and recurrence-free survival in breast cancer patients across all datasets evaluated. Importantly, these THR signatures demonstrate broad applicability across various breast cancer subtypes, grades, and treatment phases—unlike conventional prognostic markers that tend to be subtype-specific. Additionally, the THR signatures have revealed four unique patient clusters with divergent survival outcomes, three of which are ER-positive and one ER-negative. When augmented with an immune-based signature (i20), THR-70 identifies a specific ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive subtypes, as well as another ER-negative subgroup characterized by exceedingly poor survival outcomes. Conclusion The THR-based cellular ancestry signatures open a new avenue in understanding the intricacies of breast cancer biology. These signatures offer a robust and stable framework for developing other prognostic markers, thus providing an enhanced stratification of existing breast cancer categories as well as creating new classifications.
Citation Format: Mohamed Omar, Chuck Harrell, Rulla Tamimi, Luigi Marchionni, Tan Ince. Triple Hormone Receptor Signatures as Novel Prognostic Markers in Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-08.
Abstract PO3-28-09: Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?
Authors: Voros Andras , Tabar Laszlo , Bozo Renata , Olah Orsolya , Ormandi Katalin , Vereb Zoltan , Nemeth Istvan , Dean Peter B. , Puchkova Olga , Yen Ming-Fang , Chen Li-Sheng 
Published: May 2024

Abstract
Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term “invasive lobular carcinoma” implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial–mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.
Citation Format: Andras Voros, Laszlo Tabar, Renata Bozo, Orsolya Olah, Katalin Ormandi, Zoltan Vereb, Istvan Nemeth, Peter B. Dean, Olga Puchkova, Ming-Fang Yen, Li-Sheng Chen. Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-09.
Abstract PO4-05-13: Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis
Authors: Cong Binbin , Lane Jane , Cao Xiaoshan , Martin Tracey , Mansel Robert E , Davies Eleri , Jiang Wen 
Published: May 2024

Abstract
Introduction: Deleted in Liver Cancer 1 Protein, DLC1, also known as StAR Related Lipid Transfer Domain Containing 12 (StarD12), is a known negative regulator of the Rho GTPases and at the cellular level regulates cell migration. DLC1 gene transcription produces multiple isoforms of the DLC1 protein. The present study examined the clinical and prognostic implications of DLC1 isoforms, DLC1/V1/V2/V3, in relationship with Rho GTPases in human breast cancer.
Methods: Expression of three DLC1 isoforms was evaluated in a cohort of breast cancer tissues and against the clinical, pathological and clinical outcome of patients. DLC1 expression was also assessed and compared against Rho GTPases, including Rho and Rho GTP Dissociation Inhibitor (Rho GDI), in the same cohort.
Results: DLC1/V3 had a significant impact on the overall survival of patients and high levels were linked to shorter survival (Hazard Ratio=3.551 (95%CI 1.332-9.471, p=0.011), a prediction that was independent of other factors in multivariate analysis. RUC analysis demonstrated a significant predictive value for bone metastasis with DLC1/V3 (RUC=0.714, p=0.020), showing a Hazard ratio of 9.0 (1.8-44.5, p=0.007). Similarly, high DLC1/V2 expression was also linked to a shorter overall survival (p=0.035). DLC1/V2 did not show a significant correlation with bone metastasis. In contrast to V3 and V2 variants, DLC1 had a marginal overall survival benefit for the patients, in that patients with high DLC1 had a longer survival (p=0.056). DLC1/V3 had a contrasting correlation with Rho-A (r=-0.203, p=0.015) and Rho-GDI-G (r=0.194, p=0.019) and the combined expression of DLC1/V3 and RhoA/Rho-GDI-G further identified patients with poorer clinical outcome.
Conclusions: DLC1 and its variants have differing impacts on breast cancer; whereas DLC1 appears to be a tumour suppressive molecule, its variant isoform-3 was more oncogenic and a significant negative prognostic factor, together with its regulators Rho and Rho GDI.
Citation Format: Binbin Cong, Jane Lane, Xiaoshan Cao, Tracey Martin, Robert E Mansel, Eleri Davies, Wen Jiang. Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-13.
Abstract PO4-06-06: Clinical Implications of Body Mass Index (BMI) in BRCA-associated Advanced Breast Cancer Patients Treated With PARP (Poly ADP-Ribose Polymerase) Inhibitors
Authors: Mustafayev Fatma Akkoc , Munsell Mark , Layman Rachel , Yam Clinton , Barrera Angelica Gutierrez , Arun Banu 
Published: May 2024

Abstract
Background: PARP inhibitors (PARPi) have demonstrated promising results in patients with advanced as well as early breast cancer carrying germline BRCA1/2 pathogenic variants (PV). Although there is increasing attention to the effect of BMI on the outcomes of cancer patients, there is limited data on its effect on BRCA-associated advanced breast cancer patients receiving PARPi therapy. In this report, we evaluate the effect of BMI on the outcomes of advanced breast cancer patients with a BRCA PV and who received PARPi therapy. Methods: Patients with BRCA 1/2 germline PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2022 as part of their treatment for metastatic or recurrent disease were included in the analysis. The patients were divided into four groups according to BMI level as follows: underweight (&lt; 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2). Descriptive statistics, the Kaplan-Meier method, the Cox proportional hazards regression model, and Fisher’s exact test were used to report patient characteristics and outcomes. Progression-free survival (PFS) was calculated from the start of the PARPi therapy to the time of progression or death. Overall survival (OS) was calculated from the start of the PARPi therapy to the time of death of any cause. Results: One hundred and seven patients were treated with PARPi. The median BMI was 25.9 kg/m2 (14.8-61.2). In patients who received ≥2 cycles of PARPi, the overall response rate was 100% in the underweight group (n=4, 3.8%), 65.8% in the normal weight group (n=43, 41%), 64% in the overweight group (n=30, 28.6%), and 58.3% in the obese group (n=28, 26.7%). The median PFS was 5.4 months, 9.2 months, 9 months, and 8.6 months in underweight, normal weight, overweight, and obese patients, respectively. While the obese patients had a better outcome in terms of PFS (p = 0.0288), there was no significant difference observed in OS between BMI groups. Conclusion: In this analysis, we showed that obese patients with BRCA-associated advanced breast cancer had a better PFS. Future studies analyzing body composition parameters in BRCA-associated breast cancer patients treated with PARPi therapy could shed more light on the impact of obesity on outcomes.
Citation Format: Fatma Akkoc Mustafayev, Mark Munsell, Rachel Layman, Clinton Yam, Angelica Gutierrez Barrera, Banu Arun. Clinical Implications of Body Mass Index (BMI) in BRCA-associated Advanced Breast Cancer Patients Treated With PARP (Poly ADP-Ribose Polymerase) Inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-06.
Abstract PO4-07-06: Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study
Authors: Song Minji , Shin Hee Jung 
Published: May 2024

Abstract
Purpose: The aim of this study was to develop a radiomics nomogram using breast MRI data and preoperative pathologic information to predict oncotype DX recurrence score (RS) in patients with estrogen receptor-positive early-stage breast cancer (EBC).
Materials and methods: In this retrospective study, a total of 493 patients with EBC, diagnosed through core needle biopsy and who underwent preoperative breast MRI at a single institution between 2011 and 2017, were included. The patients were categorized based on RS, age at surgery, and nodal status, as suggested by the TAILORX trial, and out of the included patients, 249 were identified as likely to benefit from chemotherapy, while 244 were deemed safe to forgo chemotherapy. Radiomic features were extracted from three-dimensional segmentations of each tumor, and computer-extracted image phenotypes (CEIP) were generated from early post-contrast T1-weighted images, percent enhancement (PE) maps, and signal enhancement ratio (SER) maps. The patient cohort was divided into a training set (n=329) and a validation set (n=164). Feature selection and radiomics score construction were performed using elastic net, and a prediction model was developed using multivariate logistic regression analysis. The radiomics score, along with independent pathologic risk factors, was incorporated into a radiomics nomogram. Internal validation was conducted using an independent validation set (n=164).
Results: The radiomics score, composed of 24 selected CEIPs, demonstrated a significant association with recurrence prediction (C-index, 0.769 for training set and 0.745 for validation set). The independent pathologic predictors included in the nomogram were histology, estrogen receptor status, progesterone receptor status, nuclear grade, histologic grade, HER1, CK56, P53, and Ki67 status, with a C-index of 0.858 for the training set and 0.774 for the validation set. Adding the radiomics score to the pathologic nomogram resulted in incremental values of 0.054 and 0.092, respectively. The radiomics nomogram showed favorable prediction of low-risk RS, with a C-index of 0.912 for the training set and 0.866 for the validation set.
Conclusion: This study demonstrated that an MRI-based radiomics nomogram incorporating the radiomics score and preoperatively obtained pathologic data can effectively predict oncotype DX RS and the benefit of adjuvant chemotherapy in EBC patients. The model improves risk assessment availability and timeliness for patients with EBC.
Citation Format: Minji Song, Hee Jung Shin. Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-06.
Abstract PO4-08-03: Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations
Authors: Yoon Kyung-Hwak , Kim Eun-Kyu , Shin Hee-Chul 
Published: May 2024

Abstract
Abstract
Background: Although Breast Cancer Susceptibility Gene (BRCA)-associated invasive breast cancer has been extensively studied, there are few reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes.
Methods: Retrospective analysis was performed on a prospective cohort of 157 patients who were found positive for BRCA1/2 mutations through genetic testing from August 2003 to January 2022 at Seoul National University Bundang Hospital. Survival outcomes were compared between patients who had both invasive ductal carcinoma (IDC) and DCIS components (IDC-DCIS group, n = 121) and patients who had IDC only (IDC group, n = 36). Cox regression analysis was performed for evaluation of predictive factors for recurrence.
Results: Among the 157 patients, 65 (41.4%) patients showed BRCA1 mutations, 90 (57.3%) patients had pathological variants of BRCA2, and 2 (1.3%) patients tested positive for both BRCA1/2 mutations. There was no difference in baseline clinical characteristics between the IDC-DCIS and IDC groups. When pathological features were compared, the IDC-DCIS group was more likely to express positivity in both estrogen receptor (IDC 5 (13.9%) vs. IDC-DCIS 74 (61.2%), P &lt; 0.001) and progesterone receptor status (IDC 5 (13.9%) vs. IDC-DCIS 67 (55.4%), P &lt; 0.001). Tumors in the IDC group were associated with a higher histologic grade (P = 0.004). There was no statistically significant difference in 5-year disease-free survival between the two groups (IDC 83.6% vs. IDC-DCIS 89.3%, P = 0.989). In univariate Cox regression analysis, younger age at diagnosis was a significant predictor for recurrence (hazard ratio (HR) 2.236, P = 0.049); salpingo-oophorectomy showed a risk-reducing effect (HR 0.106, P &lt; 0.001). Further multivariate analysis found only the effect of salpingo-oophorectomy to be prognostic (HR 0.112, P &lt; 0.001). Presence of DCIS was not a risk factor for recurrence in patients with BRCA1/2 mutations (HR 1.006, P = 0.989).
Conclusion: BRCA1/2-positive breast cancer with DCIS components is more likely to be hormone receptor-positive and of lower grade compared to patients with IDC only. A tailored approach might be necessary in establishing treatment options for breast cancer patients with BRCA1/2 mutations according to the presence of DCIS.
Citation Format: Kyung-Hwak Yoon, Eun-Kyu Kim, Hee-Chul Shin. Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-03.
Abstract PO4-10-07: Understanding Psychological distress in patients prior to breast cancer diagnosis:Mixed Methods Study
Authors: Gao Yan , Gao Jinnan 
Published: May 2024

Abstract
Purpose:While the association between diagnosis of breast cancer and post-diagnosis psychological distress has been well documented, data regarding pre-diagnosis psychological distress in the breast cancer population are limited. The purpose of the current study is to measure the distress levels of patients prior to breast cancer diagnosis, to identify the categories of distress they have, and describe the experience of distress of patients before diagnosis.
Methods: This study uses a mixed research method of cross-sectional survey and qualitative interviews. In the quantitative part, a cross-sectional survey of 118 patients with completed breast biopsies awaiting pathological diagnosis was conducted using the National Comprehensive Cancer Network’s (NCCN’s) Distress Thermometer(DT) and Problem List (PL), In the qualitative part, 15 patients were invited using convenient and purposive sampling. Data was collected using a semi-structured face-to-face interview and recorded. The transcribed text was analyzed using Colaizzi's phenomenological method.
Results: The results reveal that 63.6% of patients reported a higher level of psychological distress (n=75, scoring≥4).Most patients had emotional (98%) or physical (64%) problems. Among these, worry or anxiety (47.5%), fear (33.1%), finances (21.2%), sadness and depression(18.6%), and grief or loss(15.3%) were the most frequently reported problems. Multivariate logistic regression analysis showed that the factors associated with psychological distress before the diagnosis of breast cancer patients were age, education level. The experience of patients before diagnosis emerged five themes: Very high psychological distress index; Strong uncertainty; The demand of information; Guilt for the family; Hoped for psychological support from the health care team.
Conclusions: Psychological distress is prevalent prior to breast cancer diagnosis and may merit early intervention. Understanding patients’ distress may help guide future psychosocial needs assessments and interventions to promote patient quality of life.
Table 1 Sample characteristics (n=118).
Table 2 Univariate analysis of predictors associated with psychological distress
Table 3 The binary logistic regression model of psychological distress
Citation Format: Yan Gao, Jinnan Gao. Understanding Psychological distress in patients prior to breast cancer diagnosis:Mixed Methods Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-07.
Abstract PO4-12-05: Immediate breast reconstruction is associated with reduced incidence of ipsilateral lymphedema in breast cancer patients undergoing mastectomy
Authors: Byeon Jin Young , Shin Ik Beom , Lee Hawjeong , Kang Eunhye , Jung Ji-Jung , Lim Changjin , Han Wonshik , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon 
Published: May 2024

Abstract
Purpose: The number of patients undergoing immediate breast reconstruction after mastectomy is increasing. A study of ipsilateral lymphedema after immediate breast reconstruction is also needed.This retrospective study aimed to identify the risk factors associated with lymphedema incidence after mastectomy in breast cancer patients, particularly focusing on the impact of the immediate breast reconstruction.
Methods: A retrospective analysis was conducted on 6,105 patients who underwent mastectomy for breast cancer with or without immediate breast reconstruction from Jan 2012 to Dec 2022 at Seoul National University Hospital to identify the potential risk factors for developing ipsilateral lymphedema.
Results: A total of 6,105 breast cancer patients with a mean age of 50.1 years were included in this study, with a median follow-up period of 52.0 months. In univariate analysis, the incidence of lymphedema was significantly lower in the immediate breast reconstruction group (4.47%) compared to the no reconstruction group (9.15%) (p &lt; 0.001). Other significant risk factors included the number of dissected axillary lymph nodes, number of metastatic lymph nodes, body mass index (BMI) over 25 kg/m2, the use of neo-adjuvant chemotherapy or adjuvant radiation therapy, and older age at the time of operation. In multivariate analysis, the immediate breast reconstruction remained to be an independent predictor of developing lymphedema (OR: 0.71, 95% CI: 0.55-0.91, p = 0.008), along with the number of dissected lymph nodes (OR: 1.06, 95% CI: 1.05-1.08, p &lt; 0.001), neoadjuvant chemotherapy (OR: 1.83, 95% CI: 1.44-2.33; p &lt; 0.001), adjuvant radiation therapy (OR: 6.77, 95% CI: 5.16-8.96, p &lt; 0.001), BMI &gt;25 kg./m2 (OR: 1.58, 95% CI: 1.26–1.97, p &lt; 0.001) and older age at surgery (OR: 1.01, 95% CI: 1.00-1.02, p = 0.007).
Conclusion: Our data demonstrates significantly lower rates of ipsilateral lymphedema for the patients undergoing immediate reconstruction after mastectomy when compared to that of the mastectomy alone. While these observations require further validation, our study provides useful information for the surgical decision making in patients who are considering the option of immediate reconstruction after mastectomy.
Citation Format: Jin Young Byeon, Ik Beom Shin, Hawjeong Lee, Eunhye Kang, Ji-Jung Jung, Changjin Lim, Wonshik Han, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon. Immediate breast reconstruction is associated with reduced incidence of ipsilateral lymphedema in breast cancer patients undergoing mastectomy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-05.