bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-08-15: Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening & Early Intervention: An Update of Recent Data
Authors: Whitworth Pat , Vicini Frank , Valente Stephanie , Brownson Kirstyn , Dupree Beth , Kohli Manpreet , Lawson Laura , Shah Chirag 
Published: March 2023

Abstract
Background: Breast cancer related lymphedema (BCRL) represents a dreaded complication of breast cancer treatment that can lead to morbidity, diminished quality of life, and psychosocial harm and is associated with increased costs. Increasingly, data has supported the concept of prospective BCRL surveillance coupled with early intervention to mitigate these effects. Methods: We performed a systematic review of the literature searching for published randomized and prospective data evaluating prospective BCRL surveillance with early intervention. Results: We identified 12 studies (2,907 patients) including 4 randomized trials (1,203 patients) and 8 prospective studies (1,704 patients). Randomized data consistently demonstrate that early intervention reduces rates of progression to chronic BCRL with multiple paradigms and diagnostic modalities utilized; the strongest data in the review comes from the randomized PREVENT trial which demonstrated early detection with bioimpedance spectroscopy (BIS), coupled with a compression garment applied for 12 hours a day over 4 weeks, significantly reduced the rate of chronic BCRL compared to tape measurement. Conclusions: Current data support the role of prospective BCRL surveillance with early detection and intervention to reduce rates of chronic BCRL. Breast cancer patients at risk for BCRL should undergo prospective surveillance as part of survivorship. Given the level 1 data demonstrating that BIS is superior to conventional tape measure, it should be included as the standard BCRL diagnostic modality unless an equally effective modality is employed.
Citation Format: Pat Whitworth, Frank Vicini, Stephanie Valente, Kirstyn Brownson, Beth Dupree, Manpreet Kohli, Laura Lawson, Chirag Shah. Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening & Early Intervention: An Update of Recent Data [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 P5-08-15.
Abstract P6-01-30: PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit
Authors: Markopoulos Christos , Sariyanni Mahi , Karamargiou Asimina , Antonopoulou Zoi , Tsoulos Nikolaos 
Published: March 2023

Abstract
AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found, indicating chemotherapy benefit. The aim of the present analysis was to explore in our database of lobular carcinomas analyzed with OncotypeDX, the percentage of tumors with a RS &gt;25 and test the hypothesis if Progesterone Receptor (PgR) and/or Ki-67 expression could be an indicator to have patients evaluated with OncotypeDX. PATIENTS AND METHODS: Among 2.946 patients analyzed with Oncotype DX, we found 397 patients with pure lobular carcinomas (13.47%). Ki-67 expression was obtained from 315 patients and 13 of them (4%) had a high Ki-67 value of &gt;30%. PgR expression was negative in 56 out of 397 patients (14%). We analyzed the possible relationship of RS values with PgR levels and Ki-67 expression. RESULTS: Overall, 94% of patients with ILC had a Recurrence Score ≤25 and only 6% (24/397) had a RS ≥26. There was a wide distribution of RS among patients with different values of PgR; however, there was a negative trend of Recurrence Score values and PgR expression levels. This trend was more obvious in the 56 patients with negative PgR expression. Although there were high RS values across all levels of Ki-67 expression, there was a trend towards high RS with higher Ki-67 expression; 5 out of 13 patients (38%) with ki-67 &gt;30% had a RS ≥26. CONCLUSION: Our analysis shows that the majority of lobular carcinomas of the breast have a low OncotypeDX RS, suggesting that can be treated only with hormonal therapy. However, negative or low PgR levels and high Ki-67 expression might predict a high RS and thus chemotherapy benefit and those two parameters could be used as indicators for OncotypeDX evaluation of lobular carcinomas of the breast.
Citation Format: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos. PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-30.
Abstract P6-01-41: Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer
Authors: Shah Anish , Budhathoki Pravash , Gaire Suman , Joshi Utsav , Yadav Siddhartha 
Published: March 2023

Abstract
BACKGROUND: The OncotypeDX assay analyzes the expression of 21 genes, including HER2 and Grb7, to assess the predictive effect of chemotherapy in breast cancer recurrence among women with early-stage estrogen-receptor (ER) positive/HER2-negative breast cancer. In this study, we evaluate the distribution of recurrence score from the OncotypeDX assay based on the HER2 expression status by immunohistochemistry (IHC). METHODOLOGY: Utilizing the National Cancer Database, we identified adult women with a diagnosis of stage I – III ER+/HER2- invasive ductal carcinoma of the breast between the years 2010 and 2018. Recurrence scores were classified into low (&lt; 11), intermediate (11-26), and high risk (&gt;26); and the distribution of these recurrence scores cross-tabulated with different IHC scores of HER2 expression (0, 1+, and 2+) by IHC. Women with an IHC score of 2+ had to be negative for HER2 gene amplification by FISH. Multivariate logistic regression model adjusting for age, race, origin, progesterone receptor status, grade, and cancer stage was used to assess the odds of receiving a high OncotypeDx Score (≥26). RESULT: Among 198,931 women with ER+/HER2 negative breast cancer, 59,632 (30.0%) had HER2 IHC score of 0, 102,170 (51.4%) had IHC score of 1+, and 37,129 (18.6%) women were with IHC score of 2+. The median age at diagnosis of breast cancer among all three categories of HER2 expression was 59 years. The median recurrence score for women with IHC scores of 0,1+, and 2+ was 15, 15, and 16 respectively (p &lt; 0.001). A higher proportion of women with HER2 IHC score of 2+ had a high recurrence score compared to women with an IHC score of 0 (15.2% vs. 13%, p &lt; 0.001). In multivariate analysis, compared to women with HER2 IHC score of 0, women with HER2 IHC score of 2+/FISH negative were observed to have higher Odds (OR: 1.16; 95% CI: 1.11 – 1.20, p &lt; 0.001) of receiving high recurrence score. There was no significant difference in the odds of receiving a high recurrence score between women with IHC 0+ and 1+(OR: 0.99; 95% CI: 0.96 – 1.03, p 0.82). CONCLUSION: Women with a HER2 IHC score of 2+ were observed to have a higher odds of receiving high-risk recurrence scores as compared to women with IHC score of 0. This needs to be further correlated with the response to chemotherapy and the risk of recurrence.
Citation Format: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-41.
Abstract P6-03-02: Social determinants, food deserts, and their combined contribution to breast cancer mortality
Authors: McCormack Kara 
Published: March 2023

Abstract
Recent studies have found that both food deserts (FD) and lower socio-economic status (SES) are individually associated with increased breast cancer mortality in the US. However, further work is needed to investigate their combined contribution to breast cancer mortality. Furthermore, valid inference for area-level disease mapping requires careful consideration of spatial clustering. In our study, we utilize data from the USDA Food Access Research Atlas and the American Community Survey. Breast cancer mortality data come from the National Center of Health Statistics 2014 report. We consider a latent class mixture model to determine deprivation categories which incorporate six SES proportion variables (no car, poverty, no HS graduation, crowded housing, unemployment, crowded housing), two FD (Low income and &gt; 1 mile from supermarket and receiving snap benefits and &gt; 1 mile from supermarket) variables. Our latent class model has three levels: Low, Moderate, and High, making up 36.6%, 45.6%, and 17.8% of US counties, respectively. We then incorporated these levels as a fixed effect in a Bayesian hierarchical spatial negative binomial model using R-INLA. In this model, we account for both spatially structured and unstructured effects. Counties classified as “High” on our deprivation categories were associated with a 50% increase in breast cancer mortality rates (95% CrI: [1.12, 2.02]). Also, the county proportion of women &gt;65 was significantly associated with 1.42 times higher breast cancer mortality (95% CrI [1.37, 1.42]). Policies that allow for access in the face of deprivation may contribute to lower overall breast cancer mortality.
Citation Format: Kara McCormack. Social determinants, food deserts, and their combined contribution to breast cancer mortality [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 P6-03-02.
Abstract P6-04-07: Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader Study
Authors: Salomon Anne , Nudelman Alona , Cyrta Joanna , Maklakovski Marina , Shach Anat Albrecht , Sebag Geraldine , Mallel Giuseppe , Krasnitsky Ira , Feinberg Tali , Vecsler Manuela , Sandbank Judith 
Published: March 2023

Abstract
Objective This study aimed to clinically validate the use of an AI-based solution by pathologists for the primary diagnosis of breast core needle biopsies as compared with the gold standard practice (review on the microscope). Methods A two-arm prospective reader study comparing the performance of pathologists using an AI-based solution with pathologists using a microscope was performed at two sites (different staining and digital scanners). Both arms were compared to ground truth (GT) established by the consensus of two breast pathologists. Rates of major discrepancies between each arm and GT, as determined by an adjudicating pathologist, were compared. Results Eight pathologists participated in the study and reported on 385 cases (442 HES and 330 H&E slides), each case being reported twice, once in each study arm. Pathologists first reviewed only H&E/HES slides, if requested and available, they were provided with IHCs, while the AI results were on H&E/HES only. The major discrepancy rates of the microscope arm and of the AI arm against GT were 4.42% and 3.12%, respectively, demonstrating a 29.4% reduction in major discrepancies. Pathologists with AI demonstrated very high accuracy for the detection of invasive carcinoma with sensitivity and specificity of 100% for both, as well as for DCIS/ADH with sensitivity of 92.4% and specificity of 97.8%. Conclusions This multi-site reader study reports diagnostic accuracy improvements by pathologists performing diagnosis and reporting with the support of a first read AI solution for breast biopsies. The AI solution performed accurately and generalized well for different staining platforms and different scanners. Thus, AI solutions could be used as significant aiding tools for pathologists in clinical decision-making in routine pathology practice, enhancing the quality and reproducibility of diagnosis.
Citation Format: Anne Salomon, Alona Nudelman, Joanna Cyrta, Marina Maklakovski, Anat Albrecht Shach, Geraldine Sebag, Giuseppe Mallel, Ira Krasnitsky, Tali Feinberg, Manuela Vecsler, Judith Sandbank. Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader 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 P6-04-07.
Abstract P6-08-14: Breast Cancer Treatment Choices and Results in Hispanic Women Without Funding for Radiation
Authors: Leon-Camarena Maria De Los , Reddy Neha , Ellison Kimberly , Goodgame Boone 
Published: March 2023

Abstract
Background: Although the survival rates for breast cancer have improved, there is still a disparity gap between Hispanic women and non-Hispanic women. Hispanic women in the US are vulnerable to cancer inequalities due to a plethora of barriers including disproportionate poverty, lack of health insurance, and citizenship status. A Surveillance, Epidemiology, and End Results analysis found that Hispanic women had lower rates of both early-stage breast cancer and receipts of radiation therapy (RT) after breast-conserving surgery than White women. For patients without private or government health insurance, charity and county indigent programs have variable levels of coverage, and some patients cannot access radiation services. The aim of this study is to identify disparities in breast cancer treatment for patients referred to the Travis County indigent cancer treatment program. Methods: We analyzed new referrals to the Ascension Seton Breast Clinic from April 2020 to January 2022. Demographics, disease stage, funding and treatments were extracted from medical records. We compared funding status at the time of referral vs time of surgery. We also analyzed the type of surgery elected and if RT was indicated and received. Results: We found that out of 242 referrals, 116 were diagnosed with a new malignancy. Of the 116, a total of 76 underwent breast surgery and RT was considered in 64 of these patients. 61% received RT. Of the remaining 25 patients, 16 patients elected simple mastectomies and 9 did not have funding to cover radiation (income was not low enough to qualify for RT benefit under the health district). Of the 9 women who did not have funding about 78% identified as Hispanic or Latino. 4 opted for simple mastectomies thus no longer needing RT, 3 received modified radical mastectomies without RT, 1 accessed charity funding for RT and 1 had lumpectomy without radiation and had recurrence of her breast cancer. Overall, the rate of breast conserving surgery was 43%. Discussion: The safety net system for patients in the US without access to private or government funding for healthcare is inherently limited. Costs of radiation treatment for cancer can be prohibitive for charity and indigent programs, but patients are forced to choose between mastectomy or risk a higher rate of recurrence. This data will be used to advocate for health district funding for this patient population.
Citation Format: Maria De Los Leon-Camarena, Neha Reddy, Kimberly Ellison, Boone Goodgame. Breast Cancer Treatment Choices and Results in Hispanic Women Without Funding for Radiation [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 P6-08-14.
Abstract P6-12-01: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is associated with HGF/MET signalling pathway in different subtypes of breast cancer
Authors: Yang Yiming , Sanders Andrew J. , Jiang Wen G. 
Published: March 2023

Abstract
Introduction. ALCAM (Activated Leukocyte Cell Adhesion Molecule), also known as CD166, is a cell adhesion molecule which belongs to the immunoglobulin superfamily and is widely expressed in various human tissues. It has been demonstrated that ALCAM plays an important role in the progression of malignant diseases and tumour metastasis in multiple cancer types including breast cancer. However, the molecular mechanism of ALCAM and cancer progression is currently unclear. The present study performed protein array analyses using ALCAM genetically manipulated cell models to select potential protein partners of ALCAM. The study focused on MET (Hepatocyte Growth Factor (HGF) Receptor), a prominent ALCAM interacting protein kinase and a protooncogene contributing to cancer progression and spread. Method. Human breast cancer cell lines MCF-7 and MDA-MB-231 were selected to create ALCAM knockdown cell models. A range of other breast cancer cell line with differing hormone receptor status were also used. Protein samples of transfected cells were used to perform Kinexus protein kinase microarray analysis. The protein interaction between ALCAM and other prospective protein kinases including MET was verified by the method of immunoprecipitation. Additionally, the ALCAM knockdown model was also assessed for the impact of ALCAM and HGF/MET on the biological functions by Electric Cell-substrate Impedance Sensing (ECIS). Results. MCF-7 and MDA MB-231 cells both were strongly expressed ALCAM. Cells models with ALCAM knocking down were successfully created by way of anti-ALCAM shRNA. We have shown on the protein kinase microarray analysis that the hepatocyte growth factor (HGF) receptor, MET was one of the kinases significantly affected following ALCAM knocking down. It was also found that the alteration of protein interaction between the MET protein kinase and ALCAM protein showed an opposite pattern between ER positive and ER negative ALCAM knocking down cells. This protein interaction was observed by immunoprecipitation in MDA-MB-361 and MDA-MB-231 cell lines, but not in MCF-7 cells. The biological analyses using the ECIS technologies showed that MET kinase inhibitors and exogenous recombinant HGF affected the ALCAM-mediated cell adhesion in different breast cancer subtypes. Conclusion. ALCAM is associated with HGF/MET signalling and the interaction between ALCAM and MET is different amongst subtypes of breast cancer which have different hormone receptor status.
Citation Format: Yiming Yang, Andrew J. Sanders, Wen G. Jiang. ALCAM (Activated Leukocyte Cell Adhesion Molecule) is associated with HGF/MET signalling pathway in different subtypes of 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 P6-12-01.
Abstract P6-14-05: Regulation of cellular identity and spatial organization during collective breast cancer invasion
Authors: Doak Andrea E. , Cheung Kevin J. 
Published: March 2023

Abstract
An early step in breast cancer progression is invasion of tumor cells into surrounding tissues. In many breast cancers, particularly ductal carcinomas, this invasion is accomplished by tumor cells migrating as a cohesive group. This often involves cells that take on heterogeneous roles as either leader or follower cells. While studies in common mouse and human breast cancer models have established that leader cells express high levels of keratin-14 (K14) and other basal epithelial markers, the molecular mechanisms regulating K14+ leader cell identity remain obscure. Here we performed time-sampled single cell RNA-sequencing in 3D type I collagen-embedded tumor organoids isolated from the MMTV-PyMT luminal B model of breast cancer. 11 distinct cellular transcriptional states were identified and correlated with K14 expression and invasive strand formation. Having identified the leader cell state we next asked what transcription factors were enriched, reasoning that transcription factors could be master regulators of leader cell fate. 30 different shRNAs targeting 10 genes were systematically evaluated for their effects on collective invasion. From this screen, suppression of Hes1, the downstream target of Notch signaling, yielded a marked switch from collective to single cell invasion. Disseminating single tumor cells maintained high expression of K14 in Hes1 knockdown organoids which was phenocopied by gamma-secretase inhibition in a human TNBC PDX model. Because K14+ tumor cells highly express the Notch ligand Jag1, these results support a model in which Notch signaling, specifically through activation of Hes1, dictates leader cell identity and spatial organization during collective invasion. Studies are ongoing investigating the impact of Hes1 dynamics on leader cell adhesion, hybrid EMT state, and preference for single versus collective metastasis. Because Notch suppression induces leader cell dissemination, we propose that Notch targeted therapy should be combined with therapies eradicating leader cells.
Citation Format: Andrea E. Doak, Kevin J. Cheung. Regulation of cellular identity and spatial organization during collective breast cancer invasion. [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 P6-14-05.
Abstract P6-14-10: Jagged-1 promotes breast cancer metastasis through the lymphatic system
Authors: Gordon Benjamin , Swaminathan Bhairavi , Naiche LA , Kitajewski Jan 
Published: March 2023

Abstract
While early detection of breast cancer (BC) has improved prognoses, there is an urgent need to improve outcomes for patients with distant metastatic disease. Higher expression of the Notch ligand JAG1 in primary BC tumors is strongly associated with lymph node metastasis and patient mortality, but causality is unclear. We show that JAG1 expression is higher in patients’ metastatic BC cells colonizing lymph nodes than in primary tumors, suggesting that tumor cells with high JAG1 are preferentially able to metastasize to lymph nodes. JAG1 expression is higher in a derivative of BC line MDA-MB-231 selected for tropism to lymph nodes (MDA231-LN) than in the parental line or derivatives with other tropisms. To determine the mechanism(s) of JAG1-mediated metastasis, we generated clonal JAG1 knockout cell lines from MDA231-LN cells with corresponding JAG1 rescue lines. We investigated the role of JAG1 in spontaneous metastasis under clinically relevant conditions by orthotopically implanting JAG1 knockout and expressing cells, resecting the primary tumor, and following long-term metastatic spread in a mouse model. Quantification of tumor cells in blood showed that survival, metastatic burden, and JAG1 expression did not correlate with the number of circulating tumor cells. Conversely, JAG1 expression drove an increase in lymph node and body-wide metastatic burden and a trend toward decreased survival. In this model metastatic cells were abundant throughout lymph vessels, suggesting lymphatics are the primarily route of dissemination. Preliminary transcriptional analysis suggests that JAG1 alters interactions with lymphatic endothelial cells (LEC), potentially via VEGF signaling, leading us to examine downstream events in co-cultures of LEC with lymphatically invasive BC lines. Deciphering tumor-lymphatic endothelial signaling events may open new avenues to target BC metastasis.
Citation Format: Benjamin Gordon, Bhairavi Swaminathan, LA Naiche, Jan Kitajewski. Jagged-1 promotes breast cancer metastasis through the lymphatic system [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 P6-14-10.