bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO3-12-03: SAFETY AND TOLERABILITY OF SHOCKWAVE THERAPY FOR TREATMENT OF BREAST CANCER-RELATED LYMPHEDEMA: A SYSTEMATIC REVIEW
Authors: Ventura Patricia Lima , Haddad Cinira , Nazário Afonso , Facina Gil , Sanvido Vanessa , Estevao Amanda , Rizzi Samantha Lopes de Almeida 
Published: May 2024

Abstract
Introduction: Breast cancer is currently the most common malignancy among women, after non-melanoma skin cancer. Upper limb lymphedema is the most feared complication of breast cancer treatment. Currently, the approach described in the literature as the most effective for the treatment of lymphedema is Complex Physical Therapy. In the search for more efficient therapeutic actions, Shockwave Therapy emerges as an alternative in the treatment of upper limb lymphedema secondary to breast cancer. Objective: to systematically review the available literature and verify the safety, tolerance and efficacy of using Shockwave Therapy (ESWT) in the treatment of upper limb lymphedema secondary to breast cancer. Methods: The following databases were used: PubMed; PEDro, The Cochrane Library, EMBASE, Web of science and Scopus and through manual search of articles. The PICO research method was adopted, and the descriptors adjusted according to the respective database. This study was registered in PROSPERO: CRD42020209588. Results: Combined searches, including reference lists, manual searches, and database searches, yielded 64 articles, of which 35 articles were duplicates, 23 studies were excluded by title, abstract, or full reading. Six full-text articles were selected. Of these, only 3 randomized clinical trials and 3 non-randomized clinical trials met all established inclusion criteria and were analyzed in this systematic review. Two more RCTs were added by manual search of references from other articles. None of the studies found had safety and tolerability as their primary objective, and one reported transient redness with the use of the device. Shockwave Therapy, combined with other resources, can significantly improve lymphedema volume and shoulder range of motion, but there is not enough evidence to support the use of ESWT as a substitute for complex physical therapy (CPT). Final considerations: There is evidence that it can improve ROM and upper limb volume when used in association with CPT, which is the gold standard for the treatment of lymphedema.
Keywords: Lymphedema, Breast Cancer, Extracorporeal Shockwave Therapy.
Citation Format: Patricia Lima Ventura, Cinira Haddad, Afonso Nazário, Gil Facina, Vanessa Sanvido, Amanda Estevao, Samantha Lopes de Almeida Rizzi. SAFETY AND TOLERABILITY OF SHOCKWAVE THERAPY FOR TREATMENT OF BREAST CANCER-RELATED LYMPHEDEMA: A SYSTEMATIC REVIEW [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 PO3-12-03.
Abstract PO3-15-09: LobSig4 is a superior and readily implementable ILC-focussed prognostic biomarker set
Authors: Kalinowski Lauren , Kutasovic Jamie , Srihari Sriganesh , Feng Yufan , Lal Samir , Ferguson Kaltin , Chittoory Haarika , Sokolova Anna , Lim Malcolm , De Croft Priyakshi Kalita , Lakhani Sunil , Simpson Peter , Reed Amy McCart 
Published: May 2024

Abstract
Invasive Lobular Carcinoma (ILC) is the most common special histological subtype of breast cancer. ILC typically present as Oestrogen and Progesterone Receptor positive cancers, without over-expression of HER2 and are defined by their invasive pattern of growth. Despite clinical and biological differences, including diverse sites of metastasis, ILC are managed in the same way as the more commonly diagnosed, Invasive Carcinomas of no special type. Previously, we derived the LobSig lobular specific gene signature in an attempt to prognosticate within an otherwise homogeneous tumour category. We showed that this set of genes could stratify Grade 2 and Nottingham Prognostic Index moderate tumours into high and low risk groups. Herein, we use a nanoString nCounter custom codeset and immunohistochemistry to validate the LobSig signature. Using a CoxBoost analysis we further refined the geneset to 14 genes of interest which we examined using Immunohistochemistry on a large panel of ILC with clinical follow up data. Four targets showed a significant association with breast cancer specific survival, with high levels correlating with the poorest outcomes. Considering the expression data for these 4 candidates together, we performed a Cox Proportional Hazard Regression resulting in a combined prognostic power of (P=0.00034, HR=8.07 (CI 2.58-25.30)), which has superior prognostic power over variables including tumor size and patient age. ‘LobSig4’ represents a readily implementable and informative biomarker set for prognostication in Invasive Lobular Carcinoma.
Citation Format: Lauren Kalinowski, Jamie Kutasovic, Sriganesh Srihari, Yufan Feng, Samir Lal, Kaltin Ferguson, Haarika Chittoory, Anna Sokolova, Malcolm Lim, Priyakshi Kalita De Croft, Sunil Lakhani, Peter Simpson, Amy McCart Reed. LobSig4 is a superior and readily implementable ILC-focussed prognostic biomarker set [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 PO3-15-09.
Abstract PO3-15-11: Soluble sFas, sFasL, sPD1, and sPD-L1 analyses in the blood peripheral of locally advanced breast cancer women before and after neoadjuvant chemotherapy
Authors: Vasconcelos Carolina , Salgado Marcelo , Anunciação Carlos Eduardo , Viana Denise , Torres Leuridan , de Moraes Nathália Valois Montarroyos 
Published: May 2024

Abstract
Assess soluble sFAS, sFASL, sPD1, and sPD-L1 levels in patients with HER2 or triple-negative (TN) breast cancer submitted to neoadjuvant chemotherapy. A prospective cohort study was performed with TN and HER2+ breast cancer patients between 2015 and 2018. Soluble levels of sFasL, sFas, sPD-L1, and sPD1 were collected before and after neoadjuvant chemotherapy (NAC). NAC regimens included a dense dose of Adriablastin and cyclophosphamide during four cycles, followed by Paclitaxel for 12 weeks. No clinical evidence of tumor in the breast and axillary lymph nodes was defined as a pathological complete response (pCR). Twenty-one women with TN (56,7%) and 16 (43,3%) HER2+ breast cancer were included. Twenty-one women (56.7%) presented complete pathological response (pCR) after neoadjuvant chemotherapy (NAC), defined as the absence of invasive disease in the breast and lymph nodes. High sPD1 and sFas levels in the TN and HER2+ patients compared to the control group (P&lt; 0.05). In paired analysis, statistical differences of sFas and sFasL levels in TN and HER2+ patients before and after NAC (P&lt; 0.05). Low levels of sPDL1 in HER2+ patients with pCR compared to non-pCR (P&lt; 0.05). High sFasL levels in TN patients with pCR compared to the non-pCR group (P&lt; 0.05). Conclusion: soluble sFas, sFas-L, sPD1, and sPD-L1 levels were apoptosis-related markers with potential predictive value of neoadjuvant chemotherapy response in TN and HER2+ breast cancer.
Keywords: breast cancer; FAS receptor; Programmed death 1, HER2+, Triple negative
Citation Format: Carolina Vasconcelos, Marcelo Salgado, Carlos Eduardo Anunciação, Denise Viana, Leuridan Torres, Nathália Valois Montarroyos de Moraes. Soluble sFas, sFasL, sPD1, and sPD-L1 analyses in the blood peripheral of locally advanced breast cancer women before and after neoadjuvant chemotherapy [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 PO3-15-11.
Abstract PO3-16-05: Mitochondrial DNA mutation detection in tumors and circulating extracellular vesicles of triple negative breast cancer patients for biomarker development
Authors: Vikramdeo Kunwar , Anand Shashi , Sudan Sarabjeet , Pramanik Paramahansa , Singh Seema , Godwin Andrew , Singh Ajay , Dasgupta Santanu 
Published: May 2024

Abstract
Early detection of triple-negative breast cancer (TNBC) patients and their recurrence prediction are daunting tasks. We aim to develop mitochondrial DNA (mtDNA) based biomarkers to improve the management strategies of TNBC patients. We have undertaken mitochondrial genome (MG) enrichment and next-generation sequencing approaches to map the entire MG in 73 samples (64 tissues, 9 extracellular vesicle samples) from 32 highly-aggressive TNBC patients. Measurement of mtDNA and cardiolipin contents, in concert with NDUFB8 and SDHB proteins’ expression, was carried out in tumors and matched extracellular vesicles (EVs) of all the above TNBC patients. Overall, we identified 168 nonsynonymous mtDNA mutations, of which 73% (123/186) were coding and 27% (45/168) were non-coding. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) appears to be the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19-38% TNBCs, each of which was detectable in the matched EV samples with 82% specificity. Overall, 38% of the metastatic tumor-signature mtDNA mutations were detectable in matched EVs of the TNBC patients. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI-specific mtDNA mutational load was recorded to be higher in African American (AA) compared to European American (EA) women with an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p &lt; 0.0001) content was measured in both tumors and matched EV samples along with an abundance of cardiolipin (p=0.0001) content in the EVs of the TNBC patients. Lethal tumor-signature mtDNA mutation detection and measurement of altered mtDNA and cardiolipin contents in the EVs at an early time point bear the potential to formulate noninvasive early detection and recurrence prediction strategies in TNBCs to improve the overall survival of the patients.
Citation Format: Kunwar Vikramdeo, Shashi Anand, Sarabjeet Sudan, Paramahansa Pramanik, Seema Singh, Andrew Godwin, Ajay Singh, Santanu Dasgupta. Mitochondrial DNA mutation detection in tumors and circulating extracellular vesicles of triple negative breast cancer patients for biomarker development [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 PO3-16-05.
Abstract PO3-22-10: 3D-CT mapping with a photo-translucent application using iPad delineates tumor lesions on patient breast skin in breast-conserving surgery: Preliminary results
Authors: Watanabe Gou , Suzuki Akihiko 
Published: May 2024

Abstract
Objective: The aim of this study was to evaluate the feasibility and efficacy of a 3D-CT mapping technique with a photo-translucent application using an iPad for tumor localization on the patient's breast skin in breast-conserving surgery (BCS). We also compared the accuracy of tumor localization between conventional methods and 3D-CT mapping.
Methods: Between February and July 2023, 20 female patients with early-stage (0 to 2) breast cancer scheduled for BCS were enrolled in this study. Preoperative enhanced CT scans were performed, and a 3D-CT image was generated by incorporating the patient's skin and manually marking the contrast-enhanced lesion using SYNAPSE VINCENT software. The 3D-CT images, adjusted to individual rotation angles to match the horizontal skin position above the tumor, were imported into an iPad equipped with a photo-translucent application. Using a securely fixed iPad holder, the translucent image was superimposed on the patient's breast, and the enhanced lesion was marked on the skin using a blue pen. Conventional tumor marking was performed based on ultrasound imaging, CT, and MRI findings using a black pen. Photographs were taken to simulate BCS based on the 3D-CT blue marking. All patients underwent BCS with resection margins of 1.5-2 cm from the black marking, and intraoperative frozen section analysis was performed to assess the resection margins.
Results: The majority of patients had hormone receptor-positive breast cancers, and neoadjuvant chemotherapy was administered in three patients (Table 1). The extent of tumor involvement assessed by pathological assessment and imaging findings showed the least discrepancy with MRI, with an average error of 4.2 mm. MRI also had the lowest rate of missed tumor detection compared to other imaging modalities. The initial positive margin rate was 20%, and the simulation conducted in this study did not alter that value. Furthermore, the simulation demonstrated more effective excision of the tumor's center compared to conventional surgical methods (Table 2).
Conclusion: The use of 3D-CT mapping with a photo-translucent application on an iPad offers a promising approach for accurate tumor localization in BCS. This technique provides a simplified and efficient method, and it can also be applied to cases where lesions have completely disappeared after neoadjuvant chemotherapy.

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Citation Format: Gou Watanabe, Akihiko Suzuki. 3D-CT mapping with a photo-translucent application using iPad delineates tumor lesions on patient breast skin in breast-conserving surgery: Preliminary results [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 PO3-22-10.
Abstract PO3-24-12: CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers
Authors: Freeman David , Spike Benjamin , Gates Brooke 
Published: May 2024

Abstract
Tumor progression involves the dynamic interaction between various cell types within the tumor microenvironment. Fibroblasts, which normally participate in wound healing, exhibit reciprocal communication with breast cancer cells that contributes to tumor cell plasticity and heterogeneity. Gaining insights into the molecular mechanisms underlying cell-to-cell communication, which drive cellular plasticity and play a pivotal role in breast cancer progression and metastasis, has the potential to unlock novel avenues for targeted therapeutic interventions.
The small GPI-adaptor protein CRIPTO is a key player in this context. CRIPTO orchestrates the activity of TGF-β and growth factor-like signaling pathways that activate c-Src/MEK/AKT. CRIPTO is expressed during mammary development, wound healing, and breast cancer but is largely undetectable in homeostatic tissue, making it a promising therapeutic target. Our previous studies have demonstrated that the activity of CRIPTO is contingent upon cellular stress, with pronounced influence within pro-fibrotic, hypoxic domains of tumors. Importantly, we have shown that inhibition of CRIPTO using the soluble recombinant protein antagonist A4Fc effectively impedes the progression of triple negative breast cancer (TNBC) in murine xenograft models. Building upon these findings, we have been dissecting CRIPTO‘s role in coordinating fibroblast activation and cell-state reprogramming in TNBC. Notably, we have found that inhibition of CRIPTO with A4Fc suppresses cancer associated fibroblast (CAF) activation and collagen remodeling in vivo. And, by modeling tumor cell:fibroblast crosstalk using in vitro organoid co-cultures, we have demonstrated CRIPTO expression in tumor cells is necessary for extracellular vesicle (EV) uptake by fibroblasts, their SMAD pathway activation and their priming for reciprocal signaling back to tumor cells to for transcriptional reprogramming and cellular invasion.
The significance of these findings lies in their potential to pave the way for the development of new therapies specifically targeting crucial tumor cell:fibroblast crosstalk mechanisms at primary and metastatic sites. Plasticity targeting therapies are urgently needed in the treatment of TNBC and other malignancies, and hold great promise for improving patient outcomes.
Citation Format: David Freeman, Benjamin Spike, Brooke Gates. CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers [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 PO3-24-12.
Abstract PO3-25-11: Unprecedented responses to neoadjuvant sequential administration of Tocilizumab followed by cisplatin/docetaxel for locally advanced triple negative breast cancer patients
Authors: Al-Tweigeri Taher , Alraouji Noura , Tulbah Asma , Akhtar Syed , Alzahrani Meshari , Najjar Saleh , Ajarim Dahish , Suleman Kauser , Sayed Adher Al , Aboussekhra Abdelilah 
Published: May 2024

Abstract
Background: Triple negative breast cancer (TNBC) remains a challenge for clinicians due to its aggressive behavior and scarcity of effective treatment. Interleukin 6 (IL-6) is well known to contribute to poor therapeutic gain, tumor relapse and aggressive tumor growth. Here we have explored targeting the IL-6 signaling pathway by Tocilizumab (Actemra) as a new potential therapeutic approach for the treatment of TNBC. Methods: The study population includes thirty (30) patients with (T2-T4, N0-3) stage (IIB-III) TNBC treated uniformly with Tocilizumab followed with cisplatin/docetaxel according to a traditional 3+3 design using a sentinel patient at each cohort. Eligible patients received Tocilizumab on day 1 followed by cisplatin/docetaxel on day 2 every 4 weeks for a total of six cycles. The primary end points were pathological complete response in breast and axilla (pCR) (ypT0/ypN0) and assessment for tolerability/toxicities profiles. Additionally, the status of the BRCA1 and BRCA2 genes was determined in all patients. Results: Eligible patients who were enrolled in this phase I/II trial had a median age of 42 years, with 63% premenopausal and 67% had nodal involvement at base line. The median tumor size was 45 mm (range 25-150 mm), stage III A/B 26% and stage IIIC 50%. Germline BRCA1/2 mutations represented 27%. The overall pCR and (RCB class 0+1) were 66% and 69%, respectively. Interestingly, pCR reached 81% in axilla, and 100% in patients with tumors bearing BRCA1/2 mutations. Interestingly, tocilizumab affected the blood level of several pro-carcinogenic cytokines. Conclusions: To our knowledge this novel therapeutic strategy is the first to report the inhibition of a cytokine signaling (a new class of biological therapy) in combination with chemotherapy for the intricate and hard-to-treat TNBC patients with unprecedented responses and acceptable tolerability/toxicities, which merits further investigation. Pending Patents: US Patent Application No. 18/122,839 European Patent Application No. 23 162 694.6
Citation Format: Taher Al-Tweigeri, Noura Alraouji, Asma Tulbah, Syed Akhtar, Meshari Alzahrani, Saleh Najjar, Dahish Ajarim, Kauser Suleman, Adher Al Sayed, Abdelilah Aboussekhra. Unprecedented responses to neoadjuvant sequential administration of Tocilizumab followed by cisplatin/docetaxel for locally advanced triple negative breast cancer patients [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 PO3-25-11.
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: Westergard Emily , Swenson Abigail , Schroeder Zachary , Swenson Wade 
Published: May 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.