Obstetrics and Gynecology Commons^™

Integrative Spatial Omics Reveals Distinct Tumor-Promoting Multicellular Niches And Immunosuppressive Mechanisms In Black American And White American Patients With Tnbc, Qian Zhu, Akhila Balasubramanian, Jaya Ruth Asirvatham, Megha Chatterjee, Badrajee Piyarathna, Jaspreet Kaur, Nada Mohamed, Ling Wu, Stacy Wang, Niloufar Pourfarrokh, Paula Danika Binsol, Mahak Bhargava, Uttam Rasaily, Yitian Xu, Junjun Zheng, Deborah Jebakumar, Arundhati Rao, Carolina Gutierrez, Angela R Omilian, Carl Morrison, Gokul M Das, Christine Ambrosone, Erin H Seeley, Shu-Hsia Chen, Yi Li, Eric Chang, Xiaoxian Li, Elizabeth Baker, Ritu Aneja, Xiang H-F Zhang, Arun Sreekumar

Center on Aging Staff Publications

Racial disparities in the clinical outcomes of triple-negative breast cancer (TNBC) have been well-documented, but the underlying biological mechanisms remain poorly understood. To investigate these disparities, we employed a multi-omic approach integrating imaging mass cytometry and spatial transcriptomics to characterize the tumor microenvironment (TME) in self-identified Black American (BA) and White American (WA) TNBC patients. Our analysis revealed that the TME in BA patients is marked by a network of endothelial cells, macrophages, and mesenchymal-like cells, which correlates with reduced patient survival. In contrast, the WA TNBC microenvironment is enriched in T-cells and neutrophils, indicative of T-cell exhaustion and suppressed …

Use Of Indocyanine Green Angiography To Reduce Postoperative Complications In Post-Mastectomy Breast Reconstruction: An Umbrella Review, William R. Clifton, Phil Moon, Emily V. Clifton, Julia C. Stager, Spencer R. Anderson

South Atlantic Division GME Research Day 2025

No abstract provided.

A Proteome-Wide Association Study Identifies Putative Causal Proteins For Breast Cancer Risk, Tianying Zhao, Shuai Xu, Jie Ping, Guochong Jia, Yongchao Dou, Jill E Henry, Bing Zhang, Xingyi Guo, Michele L Cote, Qiuyin Cai, Xiao-Ou Shu, Wei Zheng, Jirong Long

Faculty, Staff and Students Publications

BACKGROUND: Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk.

METHODS: We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for …

Financial Toxicity In Breast Cancer Patients Receiving Regional Nodal Irradiation: Variation By Cancer Subtype, Grace L Smith, Benjamin D Smith, Chi-Fang Wu, Simona F Shaitelman, Mariana Chavez-Macgregor, Rashmi Murthy, Kelsey Kaiser, Kimberly S Ku, Julia J Shi, Sanjay S Shete, Ying-Shiuan Chen, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Karen E Hoffman

Faculty, Staff and Student Publications

BACKGROUND: We evaluated sociodemographic and clinical predictors of financial toxicity (FT) among patients with breast cancer with higher risk clinical factors warranting regional nodal irradiation (RNI).

METHODS: Among 183 participants in a clinical trial of conventional vs. hypofractionated treatment with RNI, 125 (68 %) completed a pilot survey of FT measured using the validated Economic Strain and Resilience in Cancer (ENRICh) instrument, scored from 0 (minimal) to 10 (severe) FT. Associations with predictors were evaluated using Pearson correlation coefficients and Kruskal Wallis, Mann-Whitney U, and Jonckheere-Terpstra tests. Predictors of severe FT (ENRICh≥5) were tested using multivariable logistic regression with odds …

Survival Outcomes After Omission Of Surgery For Ductal Carcinoma In Situ, Elizabeth C Poli, Wenli Dong, Simona F Shaitelman, Nina Tamirisa, Yu Shen, Isabelle Bedrosian

Faculty, Staff and Student Publications

Clinical trials of active surveillance (AS) for Ductal Carcinoma in Situ (DCIS) are underway. We sought to understand the historical management of biologically favorable DCIS and to determine the outcomes of patients who did not have immediate surgery. Using data from the NCDB from 2004 to 2017, the selected cohort included women >40 years of age, with low or intermediate grade and hormone receptor (HR) positive DCIS. AS was defined as either no surgery or surgery >12 months from diagnosis. Women in the AS group were compared to women who had immediate surgery. A Cochran-Armitage test was used to assess …

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …

Twist1 Drives Cytotoxic Cd8+ T-Cell Exhaustion Through Transcriptional Activation Of Cd274 (Pd-L1) Expression In Breast Cancer Cells, Xiaobin Yu, Jianming Xu

Faculty, Staff and Students Publications

In breast cancer, epithelial-mesenchymal transition (EMT) is positively associated with programmed death ligand 1 (PD-L1) expression and immune escape, and TWIST1 silences ERα expression and induces EMT and cancer metastasis. However, how TWIST1 regulates PD-L1 and immune evasion is unknown. This study analyzed TWIST1 and PD-L1 expression in breast cancers, investigated the mechanism for TWIST1 to regulate PD-L1 transcription, and assessed the effects of TWIST1 and PD-L1 in cancer cells on cytotoxic CD8+ T cells. Interestingly, TWIST1 expression is correlated with high-level PD-L1 expression in ERα-negative breast cancer cells. The overexpression and knockdown of TWIST1 robustly upregulate and downregulate PD-L1 …

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …

Ndrgs In Breast Cancer: A Review And In Silico Analysis, Emilly S Villodre, Anh P N Nguyen, Bisrat G Debeb

Faculty, Staff and Student Publications

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, …

Activation Of Piezo1 Increases The Sensitivity Of Breast Cancer To Hyperthermia Therapy, Shao-Kang Wang, Xiao-Ting Zhang, Xuan-Yao Jiang, Bi-Jiang Geng, Tao-Lin Qing, Lei Li, Yun Chen, Jin-Feng Li, Xiao-Fang Zhang, Shuo-Gui Xu, Jiang-Bo Zhu, Yu-Ping Zhu, Mei-Tang Wang, Ji-Kuai Chen

Faculty, Staff and Student Publications

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress

Engineered Adoptive T-Cell Therapies For Breast Cancer: Current Progress, Challenges, And Potential, Diego F Chamorro, Lauren K Somes, Valentina Hoyos

Faculty, Staff and Students Publications

Breast cancer remains a significant health challenge, and novel treatment approaches are critically needed. This review presents an in-depth analysis of engineered adoptive T-cell therapies (E-ACTs), an innovative frontier in cancer immunotherapy, focusing on their application in breast cancer. We explore the evolving landscape of chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, highlighting their potential and challenges in targeting breast cancer. The review addresses key obstacles such as target antigen selection, the complex breast cancer tumor microenvironment, and the persistence of engineered T-cells. We discuss the advances in overcoming these barriers, including strategies to enhance T-cell efficacy. …

Targeting Eif4a Triggers An Interferon Response To Synergize With Chemotherapy And Suppress Triple-Negative Breast Cancer, Na Zhao, Elena B Kabotyanski, Alexander B Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C Reineke, Nadia Lieu, Yang Gao, Diego A Pedroza, Sebastian J Calderon, Alex J Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M Solis, Susan G Hilsenbeck, Cheng Fan, Charles M Perou, Jeffrey M Rosen

Faculty, Staff and Students Publications

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 …

Sentinel Node Biopsy For Personalized Breast Cancer Management; Advances And Controversies, Rahim Al Moushaly, Daniel Ion, Octavian Andronic, Bogdan Socea, Alexandru Cosmin Palcau, Dan Nicolae Paduraru

Journal of Mind and Medical Sciences

Sentinel lymph node biopsy (SLNB) has become the gold standard for axillary lymph node staging, providing valuable prognostic information while minimizing complications compared to axillary lymph node dissection. However, there are ongoing debates and controversies surrounding SLNB in specific cases. Studies have explored the use of SLNB in neoadjuvant chemotherapy, emphasizing the need for customized therapy decisions. Factors such as age, tumor characteristics, and treatment response influence the selection of SLNB or axillary lymph node dissection. Additionally, the presence of extranodal extension, micrometastases, and isolated tumor cells has been evaluated to determine the need for lymphadenectomy. The importance of accurate …

Cutaneous Dermal Metastasis Of Inflammatory Breast Carcinoma Mimicking Granuloma Annulare, Vikram Shaw, Jay Patel, Hanna Siatecka, Omid Jalali

Faculty, Staff and Students Publications

Breast cancer can present as a wide range of cutaneous lesions at the time of diagnosis or months to years after a known diagnosis of breast cancer. Cutaneous sequela of breast cancer, including metastasis, have a diverse range of clinical appearances. Here, we describe the case of a 59-year-old female with stage IV metastatic inflammatory breast carcinoma presenting with a chronic worsening rash on her anterior chest wall. Biopsy results demonstrated metastatic carcinoma cells within the dermal lymphatics, consistent with primary breast cancer. To our knowledge, based on a thorough review of the literature, no previous case reports detailing cutaneous …

Subsequent Female Breast Cancer Risk Associated With Anthracycline Chemotherapy For Childhood Cancer, Yuehan Wang, Cécile M Ronckers, Flora E Van Leeuwen, Chaya S Moskowitz, Wendy Leisenring, Gregory T Armstrong, Florent De Vathaire, Melissa M Hudson, Claudia E Kuehni, Michael A Arnold, Charlotte Demoor-Goldschmidt, Daniel M Green, Tara O Henderson, Rebecca M Howell, Matthew J Ehrhardt, Joseph P Neglia, Kevin C Oeffinger, Helena J H Van Der Pal, Leslie L Robison, Michael Schaapveld, Lucie M Turcotte, Nicolas Waespe, Leontien C M Kremer, Jop C Teepen

Faculty, Staff and Student Publications

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m

Stimulatory Effects Of Lycium Shawii On Human Melanocyte Proliferation, Migration, And Melanogenesis: In Vitro And In Silico Studies, Karen E Gerlach, Kanchan Ashok Phalak, Ethan O Cohen, Kiran N Chang, Roland Bassett, Gary J Whitman

Faculty, Staff and Student Publications

Rationale and objectives: Information evaluating the efficacy of 2D synthesized mammography (2Ds) reconstructions in microcalcification detection is limited. This study used stereotactic biopsy data for microcalcifications to evaluate the stepwise implementation of 2Ds in screening mammography. The study aim was to identify whether 2Ds + digital breast tomosynthesis (DBT) is non-inferior to 2D digital mammography (2DM) + 2Ds + DBT, 2DM + DBT, and 2DM in identifying microcalcifications undergoing further diagnostic imaging and stereotactic biopsy.

Materials and methods: Retrospective stereotactic biopsy data were extracted following 151,736 screening mammograms of healthy women (average age, 56.3 years; range, 30-89 years), performed between …

Toward Practical Integration Of Omic And Imaging Data In Co-Clinical Trials, Emel Alkim, Heidi Dowst, Julie Dicarlo, Lacey E Dobrolecki, Anadulce Hernández-Herrera, David A Hormuth, Yuxing Liao, Apollo Mcowiti, Robia Pautler, Mothaffar Rimawi, Ashley Roark, Ramakrishnan Rajaram Srinivasan, Jack Virostko, Bing Zhang, Fei Zheng, Daniel L Rubin, Thomas E Yankeelov, Michael T Lewis

Faculty, Staff and Students Publications

Co-clinical trials are the concurrent or sequential evaluation of therapeutics in both patients clinically and patient-derived xenografts (PDX) pre-clinically, in a manner designed to match the pharmacokinetics and pharmacodynamics of the agent(s) used. The primary goal is to determine the degree to which PDX cohort responses recapitulate patient cohort responses at the phenotypic and molecular levels, such that pre-clinical and clinical trials can inform one another. A major issue is how to manage, integrate, and analyze the abundance of data generated across both spatial and temporal scales, as well as across species. To address this issue, we are developing MIRACCL …

The Brief Case: A New Feature In Journal Of Clinical Microbiology, Makayla M Bavis, Allison M Nicholas, Alexandria J Tobin, Sherri L Christian, Robert J Brown

Faculty, Staff and Student Publications

The energy demand of breast cancers is in part met through the β-oxidation of exogenous fatty acids. Fatty acids may also be used to aid in cell signaling and toward the construction of new membranes for rapidly proliferating tumor cells. A significant quantity of fatty acids comes from the hydrolysis of lipoprotein triacylglycerols and phospholipids by lipoprotein lipase (LPL). The lipid obtained via LPL in the breast tumor microenvironment may thus promote breast tumor growth and development. In this hypothesis article, we introduce LPL, provide a meta-analysis of RNAseq data showing that LPL is associated with poor prognosis, and explain …

Crispr/Cas9 Screen Uncovers Functional Translation Of Cryptic Lncrna-Encoded Open Reading Frames In Human Cancer, Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen

Faculty, Staff and Students Publications

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was …

Short-Term Pi3k Inhibition Prevents Breast Cancer In Preclinical Models, Amy T Ku, Adelaide I J Young, Ahmed Atef Ibrahim, Wen Bu, Weiyu Jiang, Meng Lin, Laterrica C Williams, Bryant Lee Mccue, George Miles, Chandandeep Nagi, Fariba Behbod, Yi Li

Faculty, Staff and Students Publications

Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a …

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Faculty, Staff and Student Publications

No abstract provided.

Predictors Of Success In Establishing Orthotopic Patient-Derived Xenograft Models Of Triple Negative Breast Cancer, Gloria V Echeverria, Shirong Cai, Yizheng Tu, Jiansu Shao, Emily Powell, Abena B Redwood, Yan Jiang, Aaron Mccoy, Amanda L Rinkenbaugh, Rosanna Lau, Alexander J Trevarton, Chunxiao Fu, Rebekah Gould, Elizabeth E Ravenberg, Lei Huo, Rosalind Candelaria, Lumarie Santiago, Beatriz E Adrada, Deanna L Lane, Gaiane M Rauch, Wei T Yang, Jason B White, Jeffrey T Chang, Stacy L Moulder, W Fraser Symmans, Susan G Hilsenbeck, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a …

Intervention To Improve Screening Mammograms In Clinical Practice., Saida Khamooshi

DNP Scholarly Projects

Abstract

Breast cancer remains a challenging health issue in the United States, representing the second leading cause of cancer deaths for women. The key approach to tackle this issue is the early detection of breast cancer through annual mammography screening in asymptomatic women. This quality improvement project sought to improve the proportion of breast cancer screening documentation in a private obstetrics and gynecology practice that serves primarily Black women. In addition, the project is thought to improve the current utilization of office mammogram services and its mammogram completion rate. Comprehensive interventions implemented included establishing clear guidelines, staff education, using paper …

The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty

Faculty, Staff and Students Publications

Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Targeting Nuclear Hormone Receptors For The Prevention Of Breast Cancer, Cassandra L Moyer, Powel H Brown

Faculty, Staff and Student Publications

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for …

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel D Kim, Sarah M Desnyder, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

BACKGROUND: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised.

METHODS: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed.

RESULTS: Data from 1764 patients were analysed (882 patients …

Safety And Efficacy Of Hsp90 Inhibitor Ganetespib For Neoadjuvant Treatment Of Stage Ii/Iii Breast Cancer, Julie E Lang, Andres Forero-Torres, Douglas Yee, Christina Yau, Denise Wolf, John Park, Barbara A Parker, A Jo Chien, Anne M Wallace, Rashmi Murthy, Kathy S Albain, Erin D Ellis, Heather Beckwith, Barbara B Haley, Anthony D Elias, Judy C Boughey, Rachel L Yung, Claudine Isaacs, Amy S Clark, Hyo S Han, Rita Nanda, Qamar J Khan, Kristen K Edmiston, Erica Stringer-Reasor, Elissa Price, Bonnie Joe, Minetta C Liu, Lamorna Brown-Swigart, Emanuel F Petricoin, Julia D Wulfkuhle, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Adam L Asare, Jeffrey B Matthews, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van 'T Veer, Nola M Hylton, Angela M Demichele, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to …

Inclusion Of Premenopausal Women In Breast Cancer Clinical Trials, Kelsey L Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R Patel, Rachel M Layman, Sharon H Giordano, Wendy A Woodward, Benjamin D Smith, Simona F Shaitelman, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

RESULTS: Of 170 breast …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Meng Lin, Amy T Ku, Jie Dong, Fei Yue, Weiyu Jiang, Ahmed Atef Ibrahim, Fanglue Peng, Chad J Creighton, Chandandeep Nagi, Carolina Gutierrez, Jeffrey M Rosen, Xiang H-F Zhang, Susan G Hilsenbeck, Xi Chen, Yi-Chieh Nancy Du, Shixia Huang, Aiping Shi, Zhimin Fan, Yi Li

Faculty, Staff and Student Publications

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in …