bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO4-13-05: Spotlight on PSMA as a new theranostic biomarker for breast cancer
Authors: Bravaccini Sara , Cortecchia Stefania , Foca Flavia , Martinelli Giovanni , Ravaioli Sara , Tumedei Maria Maddalena , Matteucci Federica , Maltoni Roberta , Paganelli Giovanni , Poli Francesca , Puccetti Maurizio 
Published: May 2024

Abstract
Breast cancer patients are risk-stratified on the basis of the subtype classification. However, this parameter is not completely accurate in discriminating between high- and low-risk disease, creating a need for a reliable marker to determine aggressiveness. Prostate-specific membrane antigen (PSMA) could fulfill this need given that it has been reported to be expressed by breast cancer tumor cells and the endothelial cells of tumor vessels. We analyzed 68 breast cancers (BC) of whom 14 luminal A, 28 Luminal B, 15 HER2 positive and 11 triple negative BC to assess whether PSMA expression by immunohistochemistry was different in the several tumor subtypes and was related to ki67 expression and stromal TILs. PSMA positivity was calculated as the number of positive vessels on 10 fields at 40X magnifications. Kruskal Wallis’s test was used to assess difference in PSMA positivity among BC subgroups and Dunn’s test was performed for post-hoc comparisons; Spearman’s rho coefficient was calculated to analyze the correlation among PSMA, KI67 and TILs. Our results show that median PSMA was higher both considering the number of positive vessels and the staining intensity in TNBC compared to Luminal A and B tumors (p&lt; 0.001). Ki67 was higher in TNBC compared to Luminal A tumors (p&lt; 0.001). We saw a correlation between PSMA and ki67, especially in HER2+ tumors (p=0.002), while a correlation between PSMA and TILs was observed in TNBC (p=0.014). The analysis of PSMA expression on the lymph nodes showed the same trend observed for the primary tumors given that it was higher in TNBC compared to HER2 positive and luminal cancers.
Our results suggest that PSMA could be used as theranostic biomarker in BC considering that it is highly expressed in more aggressive tumors and the possibility to treat PSMA-expressing patients for anti-angiogenesis and/or radionuclide treatment.
Citation Format: Sara Bravaccini, Stefania Cortecchia, Flavia Foca, Giovanni Martinelli, Sara Ravaioli, Maria Maddalena Tumedei, Federica Matteucci, Roberta Maltoni, Giovanni Paganelli, Francesca Poli, Maurizio Puccetti. Spotlight on PSMA as a new theranostic biomarker for 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 PO4-13-05.
Abstract PO4-14-04: Comprehensive genomic profiling results in patients with metastatic breast cancer due to germline BRCA1/2 status and their HER2-low status
Authors: Tada Hiroshi , Miyashita Minoru , Harada-Shoji Narumi , Hamanaka Yohei , Sato Miku , Yanagaki Mika , Tsunokake Satoko , Motonari Tokiwa , Kon Tomomi , Yamazaki Asumi , Ishida Takanori 
Published: May 2024

Abstract
Objective: To determine the usefulness of comprehensive genomic profiling testing and the percentage of HER2-low in patients with germline BRCA1/2 (gBRCA1/2) variants metastatic breast cancer.
Methods: We included 3404 patients with metastatic recurrent breast cancer who underwent CGP testing from June 2019 to June 2023 in Japan. We examined the proportion of patients with or without recommended therapy, the proportion of patients who received matched therapy, and the proportion of patients with HER2 low by gBRCA1/2 variant due to CGP testing.
RESULTS.: Of the 3404 patients, 69 (2.0%) had gBRCA1, 136 (4.0%) had gBRCA 2, 5 (0.1%) had gBRCA1 & gBRCA2, 1807 (53.1%) were negative, and 1388 (40.1%) were untested or unknown. The overall percentage of patients who recommended targeted therapy due to CGP testing was 37.4%(1272/3404), with gBRCA1 at 31.9%(22/69), gBRCA2 at 43.4%(59/136), and gBRCA1&gBRCA2 at 50%(2/4). The percentage of matched therapy performed in the 1st line after the expert panel was 8.3% overall, 2.9% for gBRCA1, 14.0% for gBRCA2, and 0% for gBRCA1&gBRCA2. The rate of tumor mutation burden (TMB) high was 7.4% overall, and gBRCA1 at 2 .9%, gBRCA2 at 9.6%, and gBRCA1&gBRCA2 at 50%. On the other hand, the percentage of HER2-low was 38.3% overall, 29% for gBRCA1, 58.1% for gBRCA2, and 25% for gBRCA1 & gBRCA2.
Conclusion.: Germline BRCA2 variants had a higher rate of reaching matched therapy based on CGP test results. The higher rate of TMB high was suggested to be the reason for this. The high percentage of patients with HER2-low is also expected to improve the prognosis.
Citation Format: Hiroshi Tada, Minoru Miyashita, Narumi Harada-Shoji, Yohei Hamanaka, Miku Sato, Mika Yanagaki, Satoko Tsunokake, Tokiwa Motonari, Tomomi Kon, Asumi Yamazaki, Takanori Ishida. Comprehensive genomic profiling results in patients with metastatic breast cancer due to germline BRCA1/2 status and their HER2-low status [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 PO4-14-04.
Abstract PO4-20-12: Case Report: Should core needle biopsy showing primary leiomyosarcoma of the breast warrant a second look for accurate diagnosis and management?
Authors: Ritter Amanda , Shimunov Sergey 
Published: May 2024

Abstract
A 68-year-old female with unknown medical history presented to the emergency department with an exceptionally large necrotic mass of the right breast. Initial core needle biopsy showed morphology consistent with the exceedingly rare leiomyosarcoma of the breast. This patient’s necrotic, fungating tumor with abscess warranted urgent surgical excision. The pathology report that followed revealed malignant phyllodes tumor as her final diagnosis. The patient did well after surgery with no sign of metastasis and continued to follow-up with oncology. Lack of clinical guidance for breast leiomyosarcoma begs the question as to when further workup is indicated since it is known to imitate the histological and radiological features of other breast lesions. We discuss the need for updated guidance from prospective future studies to change national guidelines.
Citation Format: Amanda Ritter, Sergey Shimunov. Case Report: Should core needle biopsy showing primary leiomyosarcoma of the breast warrant a second look for accurate diagnosis and management? [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 PO4-20-12.
Abstract PO4-24-12: Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate
Authors: Nimbalkar Vidya P , VP Snijesh , Rajarajan Savitha , Alexander Annie , Ramesh Rakesh , Srinath B S , Prabhu Jyothi S 
Published: May 2024

Abstract
Background
Breast cancers (BC) in the young women tend to have poor outcomes and higher proportion of aggressive subtypes. Immunotherapy has shown promising results lately, especially for aggressive categories like triple negative breast cancers (TNBC). Success of the immunotherapy is shown to be dependent on the tumor immune microenvironment (TIME) which plays important role in disease progression and response to therapy. Though numerous studies have demonstrated immune hot tumors are associated with better prognosis, mechanism of immunologically hot TIME is not yet deciphered.
Material and methods
Gene expression data derived from RNA sequencing (n=40) of primary BC was used to divide them into immune hot and cold tumors by using 15 gene signature (Wang et al., Sci. Adv. 2021). Average expression of the hot and cold (hot=12 and cold=3) genes was derived for each tumor and median value of their ratio was used to categorize them into immunologically hot and cold tumors. Association of the hot and cold tumors with clinical characteristics was examined. CIBERSORT algorithm was used to identify immune cell subtypes and Kaplan Meier survival analysis was performed to assess the prognostic significance. Similar analysis was replicated in TCGA (n=1083) dataset.
Results
Equal proportion of immune hot and cold tumor was observed in the cohort. Higher proportion of cold tumors were observed in younger and premenopausal (p=0.002) patients. Subtype analysis showed higher proportion of cold tumors in TNBC compared to hormone receptor positive tumors (p&lt; 0.0001). No significant difference was observed in other clinicopathological characteristics between the groups. Further analysis of cold tumors for immune cell subtypes, categorized by the menopausal status showed higher proportion of plasma cells and CD4 memory resting cells and lower proportion of M2 macrophages and B memory cell in premenopausal (n=129, TCGA) compared postmenopausal (n=322, TCGA) tumors. In addition, premenopausal cold tumors were associated with better overall survival compared to postmenopausal group (p=0.001).
Conclusion
Younger premenopausal women with BC are likely to have more immunologically cold tumors. Though circulating levels of sex steroid hormones is the predominant difference between the pre and postmenopausal women, its influence on TIME and therapeutic significance must be explored.
Citation Format: Vidya P Nimbalkar, Snijesh VP, Savitha Rajarajan, Annie Alexander, Rakesh Ramesh, B S Srinath, Jyothi S Prabhu. Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate [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 PO4-24-12.
Abstract PO5-04-06: Enhancing Antitumor Activity of Her2 CAR T cells through TR2BB Co-Expression and Cytokine Signal 3 Incorporation
Authors: Chamorro Diego , Somes Lauren , Madaras Emily , Nalawade Saisha , Shafer Paul , Mosquera Andres , McKenna Mary Kathryn , Hoyos Valentina 
Published: May 2024

Abstract
Chimeric antigen receptor T cells (CARTs) targeting Her2 represent a promising approach for the treatment of patients with Her2 expressing breast cancers (BC). Her2 CARTs confront major challenges within the immune-suppressive tumor microenvironment (TME) of breast cancer, which inhibits sustained T cell proliferation and persistent antitumor activity. To bolster Her2 CARTs' expansion and persistence, we engineered a TNF-related apoptosis-inducing ligand receptor 2 (TR2) specific scFv connected to the endodomain of 4-1BB (TR2BB). TR2BB co-expressing Her2 CARTs exhibited enhanced antitumor potential against BC tumors by triggering myelod derived suppressor cell (MDSC) apoptosis, thereby remodeling the TME and promoting T cell proliferation. Despite better tumor control in mice receiving CAR.TR2BB T cells, recent trials have demonstrated the importance of incorporating a cytokine signal for optimal tumor control in patients with solid tumors. Thus, we hypothesized that we could further augment anti-tumor activity of Her2 CAR.TR2BB T cells against BC by incorporating a cytokine signal 3 through IL-15 or C7R. We engineered the CARTs to (1) ectopically produce IL-15, a crucial T-cell homeostasis and survival cytokine, and (2) express a constitutively active IL-7 receptor (C7R) that triggers IL-7 receptor signaling independently of ligand or the common receptor gamma chain (γc).
Our repeat weekly tumor challenge assay revealed that CAR.TR2BB.IL15 T cells outperformed CAR.TR2BB.C7R and CAR.TR2BB in T cell proliferation. Both CAR.TR2BB.IL15 and CAR.TR2BB.C7R exhibited improved cytotoxic potential after three weeks of antigen stimulation compared to CAR.TR2BB alone in comparison with CAR.TR2BB alone. Furthermore, in our in vivo xenograft NSG mouse models implanted with Her2 expressing breast cancer cell line and MDSCs, CAR.TR2BB.IL15 T cells showed superior tumor control and improved survival rates.
In summary, the addition of IL15 transgene to our TME targeting Her2 CARTs provides an advantage in terms of T cell persistence, proliferation, and tumor control in in vitro and in vivo models. These promising preclinical results propel us to apply this optimized Her2 targeting CART therapy in a phase I clinical trial for patients with metastatic Her2-expressing breast cancers.
Citation Format: Diego Chamorro, Lauren Somes, Emily Madaras, Saisha Nalawade, Paul Shafer, Andres Mosquera, Mary Kathryn McKenna, Valentina Hoyos. Enhancing Antitumor Activity of Her2 CAR T cells through TR2BB Co-Expression and Cytokine Signal 3 Incorporation [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 PO5-04-06.
Abstract PO5-10-02: Neighborhood deprivation index and time to initiation in patients with metastatic breast cancer
Authors: Rajendran Sneha , Ren Dianxu , Petruzzi Marina , Rosenzweig Margaret 
Published: May 2024

Abstract
Background Cyclin-dependent kinase 4 and 6 inhibitors (CDKi) are first-line therapy for patients with estrogen-positive (ER+) metastatic breast cancer (MBC). The accessibility, usability, and outcomes according to demographic factors have not been well studied in real world practice. Methods Retrospective review of patients with ER+ MBC prescribed first line CDKi therapy at a large NCI-designated cancer center from January 2015 through December 2022. Patient records were abstracted for outcomes including 1) time from CDKi prescription to drug initiation (TTI), 3) time from CDKi initiation to progression, and 3) time from CDKi initiation to death/or 6/30/2022. Patient variables collected were: patient age (continuous), race (patient self-report – Black, White, Other), partner status (Married, Not married), Insurance type (Medicare, Medicaid, Private); Mean BMI; Number of comorbidities (5 categories). Neighborhood deprivation index (NDI) was determined from the patient’s address with higher scores indicating more deprivation. Descriptive, comparative, and correlational statistics were used. Results A total of 173 patients were included in the analysis. Mean age – 63.1, (SD 12.7, range 24-94); race – White n=157, Black n=16; marital status – Married n=102, Not married n=71; mean NDI – 61.0 (SD 23.7, range 6-100); mean BMI – 28.9 (SD 6.9, range 16-48); number of comorbidities – 0 n=35, 1-2 n= 35, 3-4 n = 55, 5-6 n = 20, 7+ n = 28; insurance type – Medicare n = 115, Medicaid n = 21, Private n = 37. TTI: the median TTI was 14 days. There were no statistically significant differences in TTI based on age, race, NDI, or other demographic variables. Time to progression: in the multivariate model, younger age at diagnosis and Medicaid insurance were associated with shorter time to progression. Overall survival: not married, younger age at diagnosis, and Medicaid insurance were associated with shorter overall survival. Discussion Demographic factors are associated with diverse outcomes of MBC therapy, not attributed to delay in CDKi treatment initiation. Personalization of support during MBC illness according to risk factors for worse outcomes may help to equalize incomes.
Citation Format: Sneha Rajendran, Dianxu Ren, Marina Petruzzi, Margaret Rosenzweig. Neighborhood deprivation index and time to initiation in patients with metastatic 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 PO5-10-02.
Abstract PO5-13-02: BRCA mutational profiles of endocrine-resistant breast cancer
Authors: Karlsson Emelie , Schagerholm Caroline , Robertson Stephanie , Toosi Hosein , Sifakis Emmanouil , Hartman Johan 
Published: May 2024

Abstract
Background
Around 75% of breast cancer (BC) patients have tumors expressing the treatment-predictive biomarker estrogen receptor α (ER) and are consequently offered endocrine therapy. One-third of these patients develop endocrine resistance, a majority with tumors that retain ER expression. For most cases, the resistance mechanism is still unknown, but mutational activity is a suggested mechanism. Germline BRCA mutations are well-known in BC and are found in approximately 23% of patients with triple-negative BC and in 5% of patients with ER+ BC. However, less is certain about the somatic variants, though studies have shown prevalences of around 3% in BC. This study aimed to examine the somatic BRCA mutational profiles of endocrine-resistant paired primary and relapse tumors.
Methods
A retrospective cohort of verified endocrine-resistant BC patients was collected at Karolinska University Hospital in Stockholm, Sweden. Patients diagnosed in 2008-2012 with an ER+ and human epidermal growth factor receptor 2 (HER2) negative primary tumor and a following ER+ and HER2- relapse tumor within five years of ongoing endocrine therapy were included (N=63). DNA was extracted from archived formalin-fixed paraffin-embedded relapse and primary tumor tissue and analyzed by panel sequencing. Tumor-free lymph nodes were used as germline normal samples.
Results
The analysis showed somatic BRCA mutational activity in 38.1% of the patients. Variants were present in 20.3% of primary tumors and 30.4% of relapse tumors. BRCA1 mutations were present in 11.9% of primary tumors and 21.4% of relapse tumors. BRCA2 variations were, in turn, seen in 11.9% of primary tumors and 14.3% of relapse tumors. The frequency of patients that had alterations in both the primary and relapse tumors was 3.2% for BRCA1 and BRCA2 respectively.
Conclusion
This study of a unique endocrine-resistant BC cohort shows a high presence and varying distribution of somatic BRCA mutations in both primary and even higher in relapse tumors. These results suggest that mutational testing for possible further treatment decisions may be relevant for patients exhibiting endocrine resistance, especially in the advanced setting.
Citation Format: Emelie Karlsson, Caroline Schagerholm, Stephanie Robertson, Hosein Toosi, Emmanouil Sifakis, Johan Hartman. BRCA mutational profiles of endocrine-resistant 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 PO5-13-02.
Abstract PO5-13-11: Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast
Authors: Chan Nay Nwe Nyein , Zhan Haiying , Khaimova Revekka , Aung Thazin , Robbins Charles , Gaule Patricia , Rimm David 
Published: May 2024

Abstract
HER2 (ERBB2) is an established prognostic and predictive marker for patients with invasive breast cancer and used in HER2-targeted therapy. The clinical and biological significance of expression of HER2 protein in patients with intraductal neoplasms of the breast is not well characterized. In this study, we used our HS-HER2 (High Sensitivity-HER2) which is a CAP/CLIA certified laboratory derived test (LDT) using quantitative immunofluorescence (QIF). We evaluated HER2 expression in DCIS (ductal carcinoma in situ), LCIS (lobular carcinoma in situ) and benign lesions to correlate with their clinicopathologic characteristics. Thirty- eight cases of DCIS, and fourteen cases of LCIS and thirty benign cases were selected from the Yale Pathology department archives and 252 ROIs (regions of interest) were annotated by a board-certified pathologist. DCIS is classified according to the three-tier nuclear grading system: low, intermediate, and high-nuclear grade. LCIS is classified as PLCIS (pleomorphic variant) and CLCIS (classic LCIS) according to the WHO classification of breast tumors. Serial sections of FFPE tumor specimens were used to accurately quantify the HER2 expression by the HS-HER2 assay and the acquisition by QuPath v.04 with Qymia extension. According to the LOD (limit of detection,3 amol/mm2), LOQ (limit of quantification, 9 amol/mm2) and LOL (limit of linearity, 23 amol/mm2) of the optimized HS-HER2 assay as performed in our CLIA lab shows a broad range of HER2 expression in both DCIS and LCIS lesions, ranging from 0.7 amol/mm2 to 111.4 amol/mm2 in DCIS and 3.6 amol/mm2 to 49.9 amol/mm2 in LCIS. High grade DCIS lesions express higher average HER2 levels (111.4 + 0.7 amol/mm2) than combined low and intermediate grade DCIS (77.9 +1.9 amol/mm2) with no significant difference between low/intermediate and high-grade DCIS. CLCIS lesions express higher average HER2 level (49.9 + 3.6 amol/mm2) than PLCIS (35.1 + 5.4amol/mm2) but again this is not statistically significant. HER protein expression is relatively low in benign lesions ranging from 0.8 to 8.4 amol/mm2. Using the HS-HER2 assay, our results show quantitative level HER2 levels in DCIS and LCIS breast lesions. These findings may be important as HER2 targeted therapies that work in gene-unamplified cancer (HER2 conjugated ADCs) gain broader usage in the clinic.
Citation Format: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm. Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast [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 PO5-13-11.