tbuckley/cabot-search huggingface dataset:
Abstract PO1-22-06: Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes
Authors: Ken Ho, Joseph Ward, Chiugo Ike, Paul Thiruchelvam, Aadil Khan, Daniel Leff
Journal: Cancer Research (2024)

Abstract Background Pre-operative radiotherapy (PRT) followed by mastectomy and autologous breast reconstruction for locally advanced breast cancer has the potential to reduce the deleterious impact of radiotherapy on the reconstructed breast and expedite treatment without impact on oncologic control. The PRADA feasibility study (Lancet Oncol 2022; 23: 682-90) has previously demonstrated the technique is technically feasible and safe in modern breast oncology practice, however, there is a clear necessity for longer term outcome data to precisely determine clinical efficacy. In order to understand and appraise this evidence gap, we performed a systematic review focused on oncologic and reconstructive outcomes of PRT followed by mastectomy and breast reconstruction. Methods A prospectively registered search (PROSPERO ID: CRD42023349524) of Medline (Ovid), EMBASE (Ovid), EMCARE (Ovid) and CINAHL (EBSCO) databases was performed in August 2022 for studies reporting NART prior to mastectomy and breast reconstruction. Oncological and aesthetic outcomes were extracted with risk of bias (ROBINS-I) and methodological quality assessed (STROBE checklist) for each study. Results Twenty one published articles (18 papers and 3 abstracts) were identified reporting the outcomes of 1,126 patients with median follow-up between 19.0-212.4 months. Seventeen studies were non randomised single-centre cohort studies (12 retrospective and 5 prospective). Patients received neoadjuvant chemotherapy in 18 studies. The majority of studies were of low methodological quality and at serious risk of bias. Rates of locoregional recurrence and overall survival ranged between 0-21.7% and 79.8%-98.3% respectively. Rates of flap loss or necrosis ranged from 0-12.0%. Rates of revisional procedures ranged between 0-35.3%. Patient-reported outcomes were reported in 8 studies and were mostly ‘good’ or ‘excellent’. Conclusion The published literature described a heterogeneity of outcome for patients undergoing NART prior to mastectomy and breast reconstruction. This reflects a large number of small retrospective single-centre cohort studies of low methodological quality at risk of bias. There is a clear need for a prospective randomised controlled trial appraising the outcomes of PRT in the context of autologous breast reconstruction. Citation Format: Ken Ho, Joseph Ward, Chiugo Ike, Paul Thiruchelvam, Aadil Khan, Daniel Leff. Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes [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 PO1-22-06.
Abstract PO2-04-02: Trends in Disparities and Transitions of target therapy in Patients With ERBB2 Positive Early Breast Cancer in China and the US, 2011 to 2021
Authors: Jianbin Li, Jifang Zhou, Haibo Wang, Zhenzhen liu, Zhimin Fan, Yinhua Liu, Cuizhi Geng, Zefei Jiang
Journal: Cancer Research (2024)

Abstract Background. Diagnosis and treatment of breast cancer have been profoundly improved in China recently. However, trends in disparities and transitions of target treatment in early stage with ERBB2 positive between China and United States are not well known. Methods. This cross-sectional study used Chinese Society of clinical oncology breast cancer (CSCO BC) database from hospitals in 13 provinces of China and Flatiron database from more than 280 US community oncology clinics. Patients with ERBB2 positive and diagnosed as stage I to III breast cancer from 2011 to 2021 were collected. The distribution of target therapy was examined overall and by years. Results. A total of 10245 early-stage breast cancer with ERBB2 positive diagnosed from 2011 to 2021 were screened from the CSCO BC database(n=8446) and the Flatiron Database(n=1799). The median age at diagnosis for Chinese and US was 47 years old and 63 years old. For neoadjuvant therapy, the annual rate of trastuzumab-therapy increased from 0.4% in 2011 to 33% in 2021 in CSCO BC database, while rate of trastuzumab and pertuzumab therapy increased from 0.6% in 2016 to 42% in 2021. The proportion of trastuzumab therapy in Flatiron database decreased from 50% in 2011 to 23% in 2021, while the proportion of dual target therapy increased from 11% in 2013 to 67% in 2021. In adjuvant setting, the trastuzumab therapy increased from 6.8% in 2011 to 37% in 2021 in CSCO BC database, with highest proportion of 65% in 2018. Only 0.1% of patients received dual target therapy in 2018, the proportion increased to 32% in 2021. In Flatiron database, the trastuzumab therapy decreased from 60% in 2011 to 50% in 2021, while rate of trastuzumab and pertuzumab therapy increased from 5% in 2015 to 10% in 2021. Further follow-up is needed for survival data from two databases. Conclusions. Although significant differences were found between the China and US in target therapy, the disparities have been gradually narrowed. Use of trastuzumab in China has overtaken that in US since 2017 attributed to the effort of China's health reform in medical insurance and the promotion of guidelines. Citation Format: Jianbin Li, Jifang Zhou, Haibo Wang, Zhenzhen liu, Zhimin Fan, Yinhua Liu, Cuizhi Geng, Zefei Jiang. Trends in Disparities and Transitions of target therapy in Patients With ERBB2 Positive Early Breast Cancer in China and the US, 2011 to 2021 [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 PO2-04-02.
Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk
Authors: Raquel Granell, Sadia Haider, Matea Deliu, Anhar Ullah, Osama Mahmoud, Sara Fontanella, Lesley Lowe, Angela Simpson, James William Dodd, Seyed Hasan Arshad, Clare S Murray, Graham Roberts, Alun Hughes, Chloe Park, John W Holloway, Adnan Custovic
Journal: Thorax (2024)

Rationale Lung function in early adulthood is associated with subsequent adverse health outcomes. Objectives To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function. Methods Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV 1 /FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts. Results We identified four FEV 1 /FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV 1 /FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p&lt;0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models. Conclusions Childhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.
Abstract PO1-12-07: Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis
Authors: Megan Bradley, Mabry Nichols, Brittany Miles
Journal: Cancer Research (2024)

Abstract Breast cancer is one of the most common cancers in women and is associated with poor outcomes due to the metastatic potential of high-grade tumors. One common site of breast cancer metastasis is to the bone, leading to serious adverse effects such as bone pain, bone fracture, and spinal cord compression. Denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b (RANK) ligand (RANKL), and Pamidronate, a bisphosphonate, are two pharmacologic agents offered for the treatment of these adverse complications. The goal of this study was to conduct a retrospective cohort analysis across multiple institutions to compare the efficacy of Denosumab vs. Pamidronate in the management of osteolytic bone metastases secondary to breast cancer by evaluating the risk of adverse events. TriNetX, an online network that provides access to anonymized medical records for more than 108 million patients in 72 large healthcare organizations, was used in this study. Two cohorts, consisting of 847 patients with a diagnosis of bone metastases and breast cancer, were created and subsequently matched for age, race, gender, and ethnicity. One cohort was given Denosumab while the other was given Pamidronate, and each cohort was excluded from receiving the other medication. The occurrence of pathologic fracture in each arm, spinal cord compression, and overall five-year survival rate was measured and analyzed. The results of this study showed that Denosumab had a statistically insignificant risk reduction in both pathological fracture (2.7% vs. 2.8%, p = 0.88) and spinal cord compression (2.6% vs. 2.7%, p = 0.88) and a statistically insignificant difference in the overall five-year survival rate (45.5% vs. 52.4%, p = 0.78) when compared to Pamidronate. As a result, additional factors such as financial cost, route of administration, dosing schedule, and potential adverse side effects should be discussed with each individual who requires pharmacological therapy for bone metastases secondary to breast cancer. Citation Format: Megan Bradley, Mabry Nichols, Brittany Miles. Denosumab vs. Pamidronate in the Management of Osteolytic Bone Metastases Secondary to Breast Cancer, a Multi-Institutional Analysis [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 PO1-12-07.
Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer
Authors: Jonathan Sussman, Nathalia Y. Kim, Samantha B. Kemp, Daniel Traum, Takeshi Katsuda, Benjamin M. Kahn, Jason Xu, Il-Kyu Kim, Cody Eskandarian, Devora Delman, Gregory L. Beatty, Klaus H. Kaestner, Amber L. Simpson, Ben Z. Stanger
Journal: Cancer Research (2024)

Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component and the tumor microenvironment, which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intratumoral heterogeneity in PDAC. In this study, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest across 9 patients, capturing more than 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a proangiogenic gene signature. Taken together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche. Significance: Imaging mass cytometry revealed that pancreatic ductal cancers are composed of 10 distinct cellular neighborhoods, including a vascular niche enriched for macrophages expressing high levels of CD44 and a proangiogenic gene signature.
Abstract Wrk1-01: Agnostic trials in the field of targeted therapies
Authors: V. Subbiah
Journal: Cancer Research (2024)

Abstract Tumor-agnostic cancer therapy represents a significant shift in the field of precision oncology. It differs from conventional cancer treatments, which typically focus on specific tumor types, such as breast cancer, lung cancer, renal cell cancer, and others. This innovative approach brings hope to cancer patients by recognizing that identical genetic abnormalities can drive cancer in various parts of the body. The approvals of these therapies have introduced alternative treatment options, particularly for patients with advanced cancers and rare malignancies. Currently, six medicines have received US FDA approval for use in patients with solid tumors harboring one of five specific biomarkers. In this presentation, I will delve into the current landscape of these tissue-agnostic cancer therapies, providing a comprehensive exploration of the relevant clinical data that can enhance our understanding of these groundbreaking treatments. Citation Format: V. Subbiah. Agnostic trials in the field of targeted therapies [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 Wrk1-01.
Abstract PO1-22-10: Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases
Authors: Akiko Ogiya, Naomi Nagura, Ayaka Shimo, Hiroko Nogi, Kazutaka Narui, Hirohito Seki, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Kohei Akazawa, Tadahiko Shien
Journal: Cancer Research (2024)

Abstract Background: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of and factors associated with local recurrence (LR) after IBR. Methods: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. Results: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p &amp;lt; 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p=0.002). Conclusions: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR. Citation Format: Akiko Ogiya, Naomi Nagura, Ayaka Shimo, Hiroko Nogi, Kazutaka Narui, Hirohito Seki, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Kohei Akazawa, Tadahiko Shien. Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases [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 PO1-22-10.
Water‐Responsive Self‐Contractive Silk‐Based Skin Anti‐Aging Tensioners with Customizable Biofunctions
Authors: Yating Xie, Lele Geng, Siyuan Ni, Wei Ni, Ruizhe He, Tiantian Liu, Gai Zhang, Tiger H. Tao, Keyin Liu, Yinbo Peng
Journal: Advanced Healthcare Materials (2024)

Skin anti-aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water-responsive self-contraction capabilities, leading to the development of innovative self-contracting silk-based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self-contraction, near-infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self-contraction properties, drug-loading and sustained-release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near-infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti-aging.
Abstract PO5-06-12: Genetic screen identifies epigenetic drivers of breast cancer brain metastasis
Authors: Jocelyn Chen, Wesley Cai, Peng Xu, Don Nguyen, Qin Yan
Journal: Cancer Research (2024)

Abstract Metastatic breast cancer remains a major cause of cancer-related deaths in women, and there are few effective therapies against this advanced disease. Brain metastases, found in 15~35% of patients with breast cancer, are often incurable. Accumulating evidence suggests that key steps of tumor progression and metastasis are controlled by reversible epigenetic mechanisms. To systematically identify the druggable epigenetic regulators essential for breast cancer brain metastasis, we conducted an in vivo shRNA screen and identified multiple epigenetic regulators, including RNA acetyltransferase NAT10 as drivers of breast cancer brain metastasis. Knockdown of NAT10 significantly restrains breast cancer cell proliferation and migration in vitro and brain metastases in vivo. NAT10 promotes breast cancer cell growth through its RNA helicase activity but not its acetyltransferase activity. Integrative analyses of transcriptomics, proteomics, and NAT10 eCLIP-Seq data identify NAT10 downstream targets critical for breast cancer progression and metastasis. Thus, these results reveal novel therapeutic strategies to treat metastatic breast cancer. Citation Format: Jocelyn Chen, Wesley Cai, Peng Xu, Don Nguyen, Qin Yan. Genetic screen identifies epigenetic drivers of breast cancer brain metastasis [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 PO5-06-12.
Abstract PO1-08-09: Drynaria fortunie, a nutritional herb for prevention in triple negative breast cancer
Authors: Nitin TELANG, Hareesh Nair, George Wong
Journal: Cancer Research (2024)

Abstract Study Rationale: The triple negative breast cancer (TNBC) lacks the expression of hormone and growth factor receptors and responds only to anthracycline/taxol-based conventional chemotherapy. Major therapeutic limitations include systemic toxicity and acquired resistance to chemo-therapeutics. Relatively non-toxic nutritional herbs from traditional Chinese medicine (TCM) may represent testable alternatives against TNBC. These herbs effectively target multiple signaling pathways (Yang et al: J. Ethno-pharmacology 264: 113249, 2021). Growth inhibitory efficacy of nutritional herbs in a cellular model for TNBC is associated with downregulation of RB, RAS, PI3K and AKT signaling pathways (Telang et al: Pharmaceuticals 14: 1318, 2021). Drynaria fortunie (DF) is a nutritional herb that is used in many TCM herbal formulations. The present study is designed to examine the effects of DF in a cellular model for TNBC and to identify mechanistic leads for its efficacy. Experimental Model, herbal extract and biomarkers: Estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor-2 negative MDA-MB-231 human breast cancer cell line represented a cellular model for TNBC. Non-fractionated aqueous extract from the bark of DF represented the test agent. Cell cycle progression, RB signaling and caspase 3/7 activity represented quantitative end point biomarkers. Study Outcome: Treatment with DF at cytostatic concentrations induced S phase arrest and inhibited RB signaling via downregulated expression of cyclin E, CDK2, pRB and E2F1. DF treatment also induced caspase 3/7 activity, a marker for cellular apoptosis. Collectively, these data provide potential mechanistic leads for anti-proliferative and pro-apoptotic effects of DF in the present model. Conclusion: Present data validate a mechanism-driven experimental approach to prioritize efficacious nutritional herbs as testable alternatives for prevention/therapy of TNBC. Citation Format: Nitin TELANG, Hareesh Nair, George Wong. Drynaria fortunie, a nutritional herb for prevention 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 PO1-08-09.