tbuckley/cabot-search huggingface dataset:
Abstract PO3-27-08: Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities
Authors: Emily Westergard, Abigail Swenson, Zachary Schroeder, Wade Swenson
Journal: Cancer Research (2024)

Abstract Background: Our research examines the geographical distribution and accessibility of clinical trials for metastatic breast cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic breast cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, estimated the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed ethnicity, and other socio-economic parameters. Using GIS software, we also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic breast cancer have clinical trials within their reach. A significant 81.8% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, there is significant variation among ethnic groups, especially among American Indians, where 56.5% live within 30 miles of a clinical trial site. Conclusions: While a commendable 81.8% of the U.S. population resides within 30 miles of a metastatic breast cancer clinical trial site, our data underscores the uneven geographical spread of these trials. Our findings underscore the need for strategic initiatives to ensure clinical trials are within reach for every individual, irrespective of their location or background. Reference: 1. Galsky MD, Stensland KD, McBride RB, Latif A, Moshier E, Oh WK, Wisnivesky J. Geographic accessibility to clinical trials for advanced cancer in the United States. JAMA Intern Med. 2015 Feb;175(2):293-5. PMID: 25437434. Map of 30-, 60-, and 120-mile buffers from clinical trial sites open to patients with metastatic breast cancer. The U.S. Population living withing 30-, 60-, and 120-miles of an open clinical trial site for patients with metastatic breast cancer. Citation Format: Emily Westergard, Abigail Swenson, Zachary Schroeder, Wade Swenson. Geographic Distribution and Accessibility of Clinical Trials for Advanced-Stage Breast Cancer in the United States: A Focus on Rural and Minority Health Disparities [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 PO3-27-08.
Abstract PO1-04-06: Exposure-response analyses of sacituzumab govitecan efficacy and safety in patients with metastatic breast cancer
Authors: Indrajeet Singh, Abhishek Sathe, Paul Diderichsen, Han Witjes, Arne Van Schanke, John Maringwa, Wendy Verret, Sandhya Girish, Ahmed Othman
Journal: Cancer Research (2024)

Abstract Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate that is composed of an anti Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolysable CL2A linker. SG (10 mg/kg on D1 and D8 of every 21D cycle) is approved for patients (pts) with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in the metastatic setting). The relationship between exposure of SG, free SN-38, and total antibody (tAB) following SG administration and its efficacy and safety were evaluated in pts with HR+/HER2‒ metastatic breast cancer (mBC) and all pts with mBC (mTNBC or HR+/HER2‒ mBC), respectively. Methods: Available exposure and efficacy outcomes from HR+/HER2‒ mBC pts from phase 3 study TROPiCS-02 (n=260) and safety outcomes from mBC pts in phase 1/2 study IMMU-132-01, phase 3 study ASCENT and TROPiCS-02 (total n=569) were analyzed. Exposure-response (ER) models were developed to characterize the relationship between exposure and efficacy (complete response [CR], overall response rate [ORR], clinical benefit rate [CBR], overall survival [OS] and progression-free survival [PFS]) and safety (adverse events [AEs] of vomiting, diarrhea, hypersensitivity reactions, nausea, neutropenia, febrile neutropenia, time to first dose reduction and first dose delay) endpoints. Exposure metrics of SG, free SN-38, and tAB were evaluated as predictors and effect of clinically relevant covariates was characterized within the modeling framework. Results: Average SG-related serum exposures over the duration of treatment (until the event) were associated with significantly increased efficacy (probability of CR, ORR, CBR and longer OS and PFS) and safety events (probability of any grade AE). Neutropenia was the only AE where the increase in exposure was significantly associated with the increased probability of Grade ≥3 and Grade 4 events. Baseline Trop-2 expression level was not correlated with assessed efficacy and safety endpoints. Conclusions: Within the exposure range achieved with the 10 mg/kg regimen, higher exposure values were associated with a higher probability of achieving better efficacy. The 10 mg/kg SG dose achieved an acceptable balance between efficacy and safety which supports the appropriateness of this regimen in pts with HR+/HER2‒ mBC. Citation Format: Indrajeet Singh, Abhishek Sathe, Paul Diderichsen, Han Witjes, Arne Van Schanke, John Maringwa, Wendy Verret, Sandhya Girish, Ahmed Othman. Exposure-response analyses of sacituzumab govitecan efficacy and safety 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 PO1-04-06.
Abstract ED02-01: Biological peculiarities of ILC
Authors: C. Desmedt
Journal: Cancer Research (2024)

Abstract One in 8 women will be diagnosed with breast cancer in her lifetime and approximately 15% of them have invasive lobular breast cancer (ILC). ILC differs in many ways from the most common BC subtype, called non-special type (NST) (Van Baelen et al. Ann Oncol 2022). The microscopic hallmark of ILC is the presence of single files of relatively small discohesive tumor cells, which stems from a dysfunctional E-cadherin-catenins complex at the intercellular junctions, a feature that is uncommon in NST. More than 90% of ILC express the estrogen (ER) and/or progesterone receptor (PR) and lack HER2 amplification, while this is only the case in ~65% of NST. Patients with ILC also show a distinct clinical behavior as compared to NST: generally, a poor response to chemotherapy, more late recurrences, and a peculiar metastatic pattern. The first part of the presentation will focus on presenting the biological knowledge we have accumulated over the years about primary ILC. We will review the studies which compared ILC and NST at the genomic, transcriptomic and immune level. The second part of the presentation will be focused on metastatic breast cancer. Here we will review the published evidence regarding the metastatic dissemination of ILC, its genomic landscape and the contribution of the local tumor microenvironment. We will also dedicate attention to the important biological and clinical knowledge which can be gained by studying samples collected from patients with metastatic ILC who consented to post-mortem tissue donation. Finally, the last part of the presentation will be dedicated to mixed NST/ILC tumors. These tumors account for up to 18% of all invasive breast cancers and represent an even more under investigated area of research as pure ILC. Citation Format: C. Desmedt. Biological peculiarities of ILC [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 ED02-01.
Abstract PO4-07-07: The construction and clinical research value of the prediction model of sentinel lymph node metastasis based on indocyanine green fluorescence quantification in breast cancer
Authors: Yang Wu, Wei Zhang, Jinhai Tang
Journal: Cancer Research (2024)

Abstract Objective: To establish a prediction model of sentinel lymph node metastasis by quantitative indocyanine green fluorescence analysis in breast cancer. Methods: From May 2023 to June 2023, 20 patients with breast cancer underwent modified radical mastectomy in the General Surgery Department of Jiangsu Provincial People's Hospital were chosen for research and analysis. Sentinel lymph node were taken from all the patients. The sentinel lymph nodes were located by using the double staining method of subcutaneous injection of Methylene blue and intravenous injection of indocyanine green. The postoperative pathology is used as the standard for evaluating the presence or absence of metastatic cancer in lymph nodes. At the same time, the transcutaneous fluorescence of sentinel lymph node was recorded and the peak time of fluorescence intensity curve was plotted. To establish a logistic diagnostic prediction model and fluorescence threshold, the sentinel lymph node was incised during operation and the fluorescence of sentinel lymph node was recorded again. The criteria for ICG positive determination are determined by the Youden index, which was used to judge the lymph nodes above the threshold in the Logistic diagnostic prediction model. Lymph nodes below the threshold determined in the Logistic diagnostic prediction model are the criteria for ICG negative determination. Cases with less than 3 sentinel lymph node were excluded. Results: 19 cases were ultimately selected. Methylene blue staining data was taking as the judgment standard of sentinel lymph node. Fluorescence imaging was 100% in 14 patients, 66.7% (2/3) in 1 patient, and 125%-150% (5/4-6/4) in 4 patients. Fluorescence quantification values below 2.91 are negative lymph nodes, and values above 4.69 are positive lymph nodes. Moreover, caution is required between 2.91 and 4.69. Combining with the fluorescence dynamic attenuation curve, the positive group has a plateau curve, while the negative group mostly has a decline curve. Combining fluorescence quantification with fluorescence dynamic attenuation curve, the diagnostic rate of positive lymph nodes has a lower false negative rate compared to simple fluorescence quantification and fluorescence dynamic attenuation curve. Conclusion: The quantitative difference value of indocyanine green fluorescence angiography can be used to predict the positive metastasis of sentinel lymph node in breast cancer, making it an attempt to exempt sentinel lymph node biopsy. Citation Format: Yang Wu, Wei Zhang, Jinhai Tang. The construction and clinical research value of the prediction model of sentinel lymph node metastasis based on indocyanine green fluorescence quantification 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 PO4-07-07.
Abstract PO4-27-03: Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin
Authors: Maximilian Heinz Beck, Karoline Weiler, Sophia Ossmann, Verena Kiver, Jens-Uwe Blohmer
Journal: Cancer Research (2024)

Abstract Introduction: Limited data is available regarding the impact of margin involvement following surgery for early-stage breast cancer on distant recurrence and overall survival (OS). We therefore conducted a retrospective single-center analysis to provide further real-world evidence of margin status on OS. Methods: We systematically evaluated patients who underwent surgical intervention for early breast cancer or carcinoma in situ at Charité University Medical Center Berlin between 2006 and 2022. Our study cohort included individuals with a minimum follow-up period of 6 months and documented margin status. Patients with secondary tumors were excluded from this comprehensive analysis. Results: In our analysis, we included a total of 3767 patients, with a median follow-up duration of 72.2 months. Among these, 3443 patients underwent surgery for invasive breast cancer, while 324 patients underwent surgery for carcinoma in situ. The median overall survival (OS) for the entire cohort was 63.7 months. Specifically, patients who achieved clear margins after primary surgery exhibited a median OS of 63.5 months (n=3068), and those with free margins after secondary surgery had a median OS of 65.2 months (n=610). Conversely, patients with definitively involved margins experienced a shorter median OS of 58.6 months (n=89). The multivariate analysis revealed a statistical trend toward adverse survival outcomes for patients with definitive involved margins (Hazard Ratio 1.55; 95% CI: 0.93-2.56; p=0.090), with no statistically significant difference observed between clear margins following primary or secondary surgery. Notably, patients who underwent breast-conserving surgery demonstrated a significantly improved OS (HR 0.45; 95% CI 0.37-0.45; p&amp;lt; 0.001). Higher rates of margin involvement were observed in patients with hormone receptor-positive tumors and carcinoma in situ, while lower rates were noted in triple-negative breast cancer and after neoadjuvant chemotherapy. Implication: Our findings suggest that involved margins may be associated with a limited overall survival. Notably, patients who underwent breast-conserving therapy exhibited more favorable outcomes in our analysis, underscoring the oncologic safety of this procedure. Citation Format: Maximilian Heinz Beck, Karoline Weiler, Sophia Ossmann, Verena Kiver, Jens-Uwe Blohmer. Real-World Evidence: Impact of Margin Involvement on Overall Survival Following Breast Cancer Surgery – A Single-Center Analysis at Charité University Medical Center Berlin [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 PO4-27-03.
Abstract PO2-05-13: HER2 status presented an unstable switching from primary to recurrent breast cancer
Authors: Anjie Zhu, Hui-Ping Li
Journal: Cancer Research (2024)

Abstract Background: Breast cancer patients with HER2-2+ expression had heterogeneous characteristic. Treatment decision is of great importance after progression. Objective: We explored patients with HER2-2+ in matched primary or recurrent/metastatic tumor samples from January 2010 to June 2022 in our institute were included to evaluate the evolution from or to HER2-2+ expression. Meanwhile, with an emerging of novel entity as HER2-low expression breast cancer, we included this category when analysis as well. Results: In the cohort of a total of 159 breast cancer patients with HER2-2+ expression in either primary tumor or locoregional/distant metastases samples, HER2-2+ breast cancer accounted for 44.0% in primary tumor and 88.8% in recurrent diseases. There were 18.5% and 15.2% patients with HER2 gene amplification on ISH assay among primary and recurrent/metastatic HER2-2+ breast cancers, respectively. The overall rate of HER2 IHC discordance was 67.1%. Among primary HER2-2+ cases, 74.6% maintained in HER2-2+ when disease relapsed. Discordance was mostly driven by cases switching from HER2-2+ to HER2-1+ (64.7%). In HER2-2+ recurrent/metastatic cases, discordance was mostly driven by cases switching from HER2-0 to HER2-2+ (47.1%). The proportion of HER2 discordant cases got a higher statistically trend among HR-positive patients in compared with HR-negative patients (44.1% vs. 21.7%, p = 0.062). There were 35.0% in primary HR-positive/HER2-negative patients and 11.8% in primary triple-negative patients switching from HER2-0 to HER2-low when disease progressed, respectively. Meanwhile, HER2 discordance rate had a significant difference across different metastatic sites (p = 0.026). All contralateral breast and skin metastasis presented with discordant HER2 results. While, all central nervous system metastasis maintained the same HER2-low expression. HER2-positive phenotype in primary breast cancer samples loss their positivity in 42.1% cases. There was a total of 6.6% cases gained HER2 positivity in recurrent breast cancer samples. Conclusion: HER2 expression from primary to relapse breast cancer samples were highly unstable. Biopsy of recurrent sites was necessary to find novel treatment. Citation Format: Anjie Zhu, Hui-Ping Li. HER2 status presented an unstable switching from primary to recurrent 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 PO2-05-13.
Abstract PO1-23-11: Differential m6A modification identified by direct RNA sequencing in endocrine- resistant and sensitive breast cancer cells
Authors: Belinda Petri, Bailey Valdes, Kellianne Piell, Eric Rouchka, Carolyn Klinge
Journal: Cancer Research (2024)

Abstract A major limitation of current adjuvant treatments for the ~ 70% of breast cancer patients with estrogen receptor α–expressing (ER+) primary breast tumors is the development of acquired and adaptive endocrine therapy (ET) resistance and metastatic spread. Chemical modifications of transcribed RNAs alters their cellular location, stability, and, for mRNAs, translation into proteins. N-6 methyladenosine (m6A) is the most common modification of mRNA. We tested the hypothesis that m6A epitranscriptomic changes alters the transcriptome resulting in changes in targets in pathways contributing to the metastatic cascade in ET-resistant breast cancer cells. We used an unbiased approach of direct mRNA sequencing using the Oxford Nanopore MinION platform on polyA-selected mRNA from MCF-7 luminal A breast cancer cells and ER+, ET-resistant LCC9 breast cancer cells treated with vehicle control or 100 nM 4-hydroxytamoxifen (4-OHT) for 24 h. In addition, MCF-7 cells were treated with the METTL3 (the catalytic methyltransferase that adds the methyl group from S-adenosylmethionine (SAM) to the adenosine on the N6 position) inhibitor STM2457 to identify m6A positions and transcripts directly regulated by METTL3 activity. Computational analysis directly identified m6A locations in transcripts. We examined the differential modification rate (DMR) between MCF-7 cells +/STM2457 treatment, between MCF-7 and LCC9 cells with vehicle control treatment or with 4-OHT treatment and within each cell line with 4-OHT treatment. We identified 183 and 3,097 genes with m6A DMRs between vehicle-treated and 4-OHT-treated MCF-7 and LCC9 cells, respectively. For 4-OHT-treated cells, we identified 2,401 and 2,638 genes with m6A DMRs in MCF-7 and LCC9 cells respectively with 1,760 genes in common. We identified many genes with multiple m6A modifications, e.g., AMIGO2 appeared to have 14 m6A sites at DRACH motifs in MCF-7 cells, but none were m6A modified in LCC9 cells. Enrichment by Pathway Maps, Process Networks, and GO Processes were performed. Overall, our data suggest a role for altered m6A positions in transcripts and pathways involved in ET-resistance in breast cancer. Citation Format: Belinda Petri, Bailey Valdes, Kellianne Piell, Eric Rouchka, Carolyn Klinge. Differential m6A modification identified by direct RNA sequencing in endocrine- resistant and sensitive breast cancer 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 PO1-23-11.
Abstract PO3-26-02: Identification of a novel, brain penetrant, EGFR sparing, ErbB2 inhibitor with activity against oncogenic ErbB2 mutations
Authors: Mark J. Chicarelli, Ben Arwood-Levine, Tanna Bettendorf, Karyn Bouhana, Richard Brizendine, LouAnn Cable, Michelle Crow, Brad Fell, John Fischer, Jennifer Fulton, Anna Guarnieri, Madison Hillman, Ravi Jalluri, Daniel Krischlunas, Keith Koch, Vijay Kumar, Cori Malinky, Rob Rieger, John Robinson, Lee Stunkard, Francis Sullivan, Roy Turton, Logan Vine, Shannon Winski, Yeyun Zhou
Journal: Cancer Research (2024)

Abstract Alterations in ErbB2 have an established role as oncogenic drivers in many solid tumors, including gastric and breast cancer. While ErbB2 amplification is well recognized, activating ErbB2 mutations including exon 20 YVMA insertions, S310F/Y, L755S, V777L, and V842I, have emerged as mutually exclusive oncogenic drivers. ErbB2 mutations are present in ~3-4% of breast cancers and are now recognized as known mechanisms of acquired resistance to ErbB2 targeted therapies. These alterations can also be found in metastastic breast cancer that has advanced to the brain, a major clinical challenge with few therapeutic options. Unfortunately, many approved ErbB2 inhibitors are limited in their utility due to the inhibition of wild type EGFR resulting in severe rash and diarrhea. Herein, we describe preclinical data on a brain penetrant, wild type EGFR sparing, ErbB2 inhibitor with activity against prevalent mutations including exon 20 YVMA insertions. Citation Format: Mark J. Chicarelli, Ben Arwood-Levine, Tanna Bettendorf, Karyn Bouhana, Richard Brizendine, LouAnn Cable, Michelle Crow, Brad Fell, John Fischer, Jennifer Fulton, Anna Guarnieri, Madison Hillman, Ravi Jalluri, Daniel Krischlunas, Keith Koch, Vijay Kumar, Cori Malinky, Rob Rieger, John Robinson, Lee Stunkard, Francis Sullivan, Roy Turton, Logan Vine, Shannon Winski, Yeyun Zhou. Identification of a novel, brain penetrant, EGFR sparing, ErbB2 inhibitor with activity against oncogenic ErbB2 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 PO3-26-02.