tbuckley/cabot-search huggingface dataset:
Abstract PO4-25-05: LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth
Authors: Alexis Elfstrum, Annisa Rumahorbo, Braedan McCluskey, Emma Nelson, Kaylee Schwertfeger
Journal: Cancer Research (2024)

Abstract Macrophages represent a heterogeneous myeloid population with varied functions in normal tissue and tumors. We identify a tissue resident macrophage subpopulation marked by the protein LYVE-1 in both the female mammary gland and mammary tumor. In a genetic LYVE-1+ macrophage deletion model, loss of LYVE-1+ macrophage leads to accumulation of the extracellular matrix glycosaminoglycan hyaluronan. Further, qRT-PCR of tissue lacking LYVE-1+ macrophages yields a gene signature associated with extracellular matrix disorganization. Supporting a tissue remodeling functionality, inducing a LYVE-1 macrophages phenotype in vitro prompts HA internalization and increases hyaluronidase expression. In a murine tumor model, deletion of LYVE-1+ macrophages slows tumor progression and increases HA accumulation, suggesting an anti-tumorigenic, tissue remodeling phenotype. LYVE-1+ macrophages preferentially localize to HA dense regions of tumors, specifically in the tumor stroma, while scRNA-seq of murine tumors demonstrates a LYVE-1+ macrophage phenotype associated with tissue remodeling and immunosuppression. Our data illustrate a LYVE-1+ macrophage population critical for HA homeostasis and tumor progression. Citation Format: Alexis Elfstrum, Annisa Rumahorbo, Braedan McCluskey, Emma Nelson, Kaylee Schwertfeger. LYVE-1 expressing macrophages modulate the extracellular matrix and contribute to mammary tumor growth [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 PO4-25-05.
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: Taher Al-Tweigeri, Noura Alraouji, Asma Tulbah, Syed Akhtar, Meshari Alzahrani, Saleh Najjar, Dahish Ajarim, Kauser Suleman, Adher Al Sayed, Abdelilah Aboussekhra
Journal: Cancer Research (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 PO1-27-09: TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 RESULTS
Authors: Ronald Limon, Mariano Lopez-Pereyra, Mario Gianella, Neysa Espinoza, Denize Ramirez, Carlos Antelo, Claudia Sitic, Wara Cortez, Oscar Niño De Guzman, Silvia Neciosup, Natalia Valdivieso
Journal: Cancer Research (2024)

Abstract Background. Premenopausal women with high risk early stage BC HR+/Her2- present as a complex disease and generally have worse survival outcomes compared to postmenopausal women with the same disease. There are pathological clinical factors and genomic platforms that help us in therapeutic decisions. The use of triptorelin 3.75mg associated with AI promotes favorable results in terms of survival for premenopausal women with high-risk Early stage BC. TEXT/SOFT trial. TRIPTO3 study evaluates the use of Triptorelin 11.25mg vs. Triptorelin 3.75mg in this specific patient population. Methods: We reviewed medical records of premenopausal female patients with high-risk early stage breast cancer who have been treated and received triptorelin 3.75mg and triptorelin 11.25mg as part of their treatment. All patients were treated at a private Oncology Center between 2013 and 2020. The primary objective was disease-free survival. Results: 52 patients were found who met the inclusion criteria. 28(53.8%) patients received triptorelin 11.25mg and 24(46.2%) patients received triptorelin 3.75mg respectively. The median follow-up was 63 months and the disease-free survival for the Triptorelin 11.25mg group was 91.2% and for the Triptorelin 3.75mg group was 86.8% respectively (Hazard Ratio of disease-free survival was 1.2; 95% IC (0.2-7.2). Disease-free survival for both groups regardless of triptorelin dose was 89% at 5 years. The median disease-free survival was not reached in both groups. Conclusions: Our findings show that triptorelin 11.25 mg is similar to the use of triptorelin 3.75 mg in terms of disease-free survival for premenopausal women with high-risk early stage breast cancer. Citation Format: Ronald Limon, Mariano Lopez-Pereyra, Mario Gianella, Neysa Espinoza, Denize Ramirez, Carlos Antelo, Claudia Sitic, Wara Cortez, Oscar Niño De Guzman, Silvia Neciosup, Natalia Valdivieso. TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 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 PO1-27-09.
Abstract ED03-01: Breaking the Obesity-Breast Cancer Link: Comparing Diet, Drug and Surgical Approaches
Authors: S. Hursting
Journal: Cancer Research (2024)

Abstract The prevalence of obesity, an established risk and progression factor for at least 15 types of cancer (including breast cancer), continues to rise in the US and many other countries. Lifestyle approaches to weight loss have proven challenging for most people to maintain, and bariatric surgery, while effective, is expensive and has numerous adverse effects. The recent availability of highly effective incretin therapies for weight loss raises several key questions that we will address, including: i) do these agents drive weight loss in obese female mice?; ii) do they reverse obesity-induced metabolic dysregulation?; iii) can they reverse obesity-driven cancer?; iv) how heterogeneous is the response to these agents? We will report our study of the effects of extended (13 weeks) tirzepatide (TZP, a dual GLP1R/GIPR agonist) treatment in obese female mice on weight loss, metabolic hormones, and mammary tumor growth. We found that—similar to reports in the literature using male mice—obese female mice lost &amp;gt;20% body weight by 4 weeks of TZP treatment. Moreover, TZP-induced weight loss was maintained through 13 weeks of treatment by progressively escalating the dose up to 40 nmol/kg. Congruent with reports in male rodents and humans, we found the majority of weight loss in female mice was attributed to loss of adipose tissue, rather than lean mass. The effects of TZP on body weight and composition were associated with reversal of obesity-induced changes in glycemic control and circulating levels of metabolic hormones, particularly leptin, insulin, and IGF-1. TZP also significantly reversed the protumor effects of obesity in our murine E0771 orthotopic transplant model of TNBC.Furthermore, daily 30% calorie restriction, which we previously reported has strong weight loss-inducing, metabolic reprogramming and anticancer effects in multiple mouse models of breast and other cancers, reversed body weight, adiposity, and TNBC tumor growth and altered metabolic hormones to a greater extent than all groups studied, including the never-obese control mice and TZP-treated mice. Citation Format: S. Hursting. Breaking the Obesity-Breast Cancer Link: Comparing Diet, Drug and Surgical Approaches [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 ED03-01.
Abstract PO3-16-04: Distribution of intrinsic subtypes in endocrine-resistant and endocrine-sensitive breast cancer
Authors: Caroline Schagerholm, Stephanie Robertson, Emelie Karlsson, Emmanouil Sifakis, Johan Hartman
Journal: Cancer Research (2024)

Abstract Background Breast cancer (BC) is a heterogeneous disease that can be divided into intrinsic molecular subtypes. Among the four intrinsic subtypes, Luminal A and Luminal B are the most common and associated with the best outcome, whereas HER2-enriched and basal-like are less frequent. Tumors that are estrogen receptor α (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) are mostly found among the luminal subtypes. Despite that patients with ER+/HER2- tumors are offered adjuvant endocrine therapy, around one-third eventually develop endocrine resistance. The aim of this study was to explore the distribution of intrinsic subtypes in endocrine-resistant primary and relapse tumors, comparing these to endocrine-sensitive controls. Materials and methods Verified endocrine-resistant BC patients diagnosed in 2008-2012 were retrospectively collected at the Karolinska University Hospital, Stockholm, Sweden. Cases (N=70) were identified as patients with ER+/HER2- primary tumors and subsequent ER+/HER2- relapse tumors within 5 years and during endocrine therapy. Patients with primary ER+/HER2- tumors without progression or relapse at 10 years of follow-up were defined as controls (N=78), diagnosed in 2005-2006. Extracted RNA from formalin-fixed paraffin-embedded tumor tissue was analyzed by Affymetrix Clariom D Microarray and assessed by Transcriptome Analysis Console and R software. Results Among the controls, the distribution of Luminal A, Luminal B, and HER2-enriched subtypes was 65.4%, 34.6%, and 0%, respectively. In primary tumors, the distribution was in turn 55.4%, 43.1%, and 1.5%, and among relapse tumors 57.6%, 37.9%, and 4.5%, respectively. A total of 19 cases, accounting for 27.1%, switched intrinsic subtypes between the paired primary and relapse tumors. No tumors exhibited the basal-like subtype. Conclusion In this unique cohort, Luminal B and HER2-enriched subtypes were more common in primary and relapse tumors of verified endocrine-resistant patients than in primary tumors of endocrine-sensitive controls. Further, the HER2-enriched subtype, although sparse, was more frequently found in patients’ relapse tumors than in their corresponding primary tumors, and over one-fourth of cases switched subtypes during progression. These findings support the presence of subtype shifting in endocrine-resistant relapses and that endocrine-resistant tumors are more prone to be of Luminal B or HER2-enriched subtypes than endocrine-sensitive tumors. Citation Format: Caroline Schagerholm, Stephanie Robertson, Emelie Karlsson, Emmanouil Sifakis, Johan Hartman. Distribution of intrinsic subtypes in endocrine-resistant and endocrine-sensitive 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 PO3-16-04.
Abstract PO3-24-08: Establishment of a selective culture method for breast cancer stem cells derived from patient tissue and a subgroup analysis of cancer stem cells
Authors: Satoshi Sueoka, Takayuki Kadoya, Kai Azusa, Shinsuke Sasada, Akiko Emi, Morihito Okada, Yukino Kobayashi, Koh Nakayama
Journal: Cancer Research (2024)

Abstract Purpose Cancer stem cells are considered to cause recurrence and metastasis due to their resistance to drug and radiation therapy. Breast cancer stem cells are therefore the true target for the treatment of breast cancer. In this study, we established a method to selectively culture breast cancer stem cells from patient-derived breast cancer tissue, and we analyzed their characteristics using immunostaining to identify gene expression. Method Breast cancer tissues from ER+, HER2- and drug-naive patients were fragmented and cultured using low-adherent plates (spheroid culture). We investigated the stemness of the breast cancer cells obtained by the spheroid culture by immunostaining the breast cancer stem cell markers and examining their proliferation and differentiation in a mouse transplantation model. The diversity of the cells was further examined by means of the expression of the EMT markers and genetic analysis. Results In 48 cases, the proportion of CD44+/CD24- breast cancer cells increased from 13.8% to 61.6% in the spheroid culture. In addition, even small numbers of cells obtained by the spheroid culture were transplanted into mice, and the transplanted cells subsequently differentiated in the mice, demonstrating their stemness. ER expression was negatively changed in 52.1% of cases, and the expression of EMT markers, Twist, Snail, and Vimentin, was increased from 43.8% to 75.0%, 12.9% to 58.1%, and 7.71% to 37.7%, respectively. A DNA microarray with 14 cases showed that breast cancer stem cells obtained from ER+ and HER2- breast cancer tissue were classified into two groups. Conclusion We demonstrated that breast cancer stem cells were selectively cultured from patient-derived breast cancer tissue in a spheroid culture. Furthermore, breast cancer stem cells have different characteristics from breast cancer cells in primary tumors and are diverse at an EMT level, and in genetic analyses. Table. Expression of primary tumors and spheroids Citation Format: Satoshi Sueoka, Takayuki Kadoya, Kai Azusa, Shinsuke Sasada, Akiko Emi, Morihito Okada, Yukino Kobayashi, Koh Nakayama. Establishment of a selective culture method for breast cancer stem cells derived from patient tissue and a subgroup analysis of cancer stem 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 PO3-24-08.
Abstract PO3-15-09: LobSig4 is a superior and readily implementable ILC-focussed prognostic biomarker set
Authors: 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
Journal: Cancer Research (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 ED05-03: Surgical management of Stage I TN and HER2+ breast cancer
Authors: A. Mamtani
Journal: Cancer Research (2024)

Abstract The management of early-stage triple-negative (TN) and HER2-positive (HER2+) breast cancer has evolved significantly with continually improving systemic therapies. The use of neoadjuvant chemotherapy (NAC) has become standard for stage II disease, for both surgical downstaging and assessment of response to treatment, allowing for tailoring of systemic therapy in the adjuvant setting. However, the optimal treatment approach for stage I TN and HER2+ disease remains controversial, given the limited burden of disease at presentation with most patients considered candidates for limited surgery, and the excellent overall outcomes with de-escalated systemic therapy regimens in the adjuvant setting. This presentation will discuss the evolving landscape and current standards for stage I TN and HER2+ disease. Citation Format: A. Mamtani. Surgical management of Stage I TN and HER2+ 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 ED05-03.
Abstract PO3-15-01: Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative breast cancer
Authors: Wei Wang, Deyue Liu, Shuning Ding, Yan Fang, Jiayi Wu, Li Zhu
Journal: Cancer Research (2024)

Abstract Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with high malignancy and poor outcome. Resistance to chemotherapy leads to treatment failure. How to overcome drug resistance is the key point in TNBC treatment. Previously, we initiated a prospective multicenter single-arm NeoPath clinical study (ClinicalTrial.gov identifier: NCT03907800) to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of triple negative and HER2-positive early breast cancer. A total of 99 TNBC patients were enrolled and the pCR rate in TNBC was 33.78%. Samples before and after treatment were collected. RNA-sequencing results showed that OST4 was of high-expression in drug-resistant TNBC tumor tissues compared with chemo-sensitive samples. To verify the clinical significance of OST4 expression levels in TNBC, we tested the expression of OST4 by immunohistochemical technique on a tissue microarray including 87 TNBC cases treated with chemotherapy. We found that high expression of OST4 was associated with poor tumor differentiation, and patients with high OST4 expression had more relapse after chemotherapy. Ex-vivo proliferation assay and foci formation assay further confirmed that over-expression of OST4 promoted chemo-resistance, whereas down-regulating OST4 could reverse resistance in TNBC cell lines. As an oligosaccharyltransferase, it is reported that OST4 played parts in N-glycosylation. So we try to elucidate the relationship between N-glycosylation and drug resistance. Glycoproteomics results verified the existence of differential N-glycosylation atlas in drug-resistant tumor tissues compared with drug sensitive samples. NGS1 was identified as a potential target of OST4 by co-immunoprecipitation and mass spectrometry. In conclusion, high expression of OST4 could promote chemotherapy resistance in TNBC trough N-glycosylation regulation. Targeting OST4 may help reverse drug-resistance and improve therapeutic effect in TNBC. Citation Format: Wei Wang, Deyue Liu, Shuning Ding, Yan Fang, Jiayi Wu, Li Zhu. Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative 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 PO3-15-01.
Abstract PO1-20-11: Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report”
Authors: Jesus Flores Banda, Kavitha Donthireddy
Journal: Cancer Research (2024)

Abstract A 38-year-old breastfeeding female with no family history of breast or gynecological cancer presented to her PCP with a 4-month history of galactorrhea and enlarged left-sided breast mass. On physical exam, a 4-inch round complex, nonmobile, non-tender mass in the left breast and bloody-to-pink discharge from the nipple was present on the exam. Diagnostic mammogram and US revealed BIRADS 5, microcalcifications consistent with DCIS, 4-cm mass, with a positive lymph node (LN), and needle core biopsy of both breast and LN, showed DCIS and metastatic carcinoma, respectively. Further workup did not show distant or skeletal metastatic disease. Therefore, a diagnosis was made, and the patient was provided a clinical-stage cT3, cN2, cM0, ER+, PR-, and HER2+. The patient completed neoadjuvant therapy with TCHP and underwent a left lumpectomy with sentinel LN biopsy. Additionally, pathology diagnosis showed scant residual DCIS (10mm) and no metastatic disease in the LN. After that, the patient completed adjuvant radiotherapy and was placed on adjuvant therapy with trastuzumab and pertuzumab. In conclusion, any breast abnormality reported by a pregnant or breastfeeding woman should not be neglected and assumed that it is a regular and physiological change until proven otherwise. Future proposals include guidelines for managing abnormal breast findings during pregnancy. Citation Format: Jesus Flores Banda, Kavitha Donthireddy. Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report” [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 PO1-20-11.