Scholars@Duke
Amanda Van Swearingen

Amanda Van Swearingen

Research Program Leader, Sr
Medicine
amanda.vanswearingen@duke.edu
232 Baker House, Trent Drive, Box #3381, Durham, NC 27710
20 Sydenham Road, Durham, NC 27713

Selected Publications

Unique genomic alterations in the circulating tumor DNA of patients with solid tumors brain metastases.

Journal Article Neurooncol Adv · 2024 BACKGROUND: Although serum circulating tumor DNA (ctDNA) is routine, data from patients with brain metastases (BrMs) is limited. We assessed genomic alterations in ctDNA from patients with solid tumor BrMs in 3 groups: Isolated BrMs with stable extracrania ... Full text Link to item Cite

Triple Negative Breast Cancer and Brain Metastases.

Journal Article Clin Breast Cancer · December 2023 The treatment of metastatic breast cancer (MBC) has improved over the past decade, however prognosis continues to be mitigated by the fact that about 1 in 5 patients with MBC will develop brain metastases (BrM) during their metastatic disease course. 1 Thi ... Full text Link to item Cite

The Enduring Effects of COVID for Cancer Care: Learning from Real-Life Clinical Practice.

Journal Article Clin Cancer Res · May 1, 2023 For three years, COVID-19 has circulated among our communities and around the world, fundamentally changing social interactions, health care systems, and service delivery. For people living with (and receiving treatment for) cancer, pandemic conditions pre ... Full text Link to item Cite

Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan.

Journal Article NPJ Breast Cancer · March 30, 2023 Leptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinic ... Full text Link to item Cite

Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.

Journal Article Clin Cancer Res · January 4, 2023 PURPOSE: Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the an ... Full text Link to item Cite

Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2 + breast cancer.

Conference Breast cancer research and treatment · January 2023 PurposeCurrent systemic therapy guidelines for patients with HER2 + breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2 + BCBrM has ne ... Full text Cite

Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases.

Journal Article Curr Treat Options Oncol · October 2022 Brain metastasis arising from breast cancer is associated with a poor prognosis. Various systemic chemotherapy and targeted therapies which are effective against breast cancer often fail to provide benefits against brain metastasis. This is mainly due to l ... Full text Link to item Cite

Comprehensive Analysis of the Immunogenomics of Triple-Negative Breast Cancer Brain Metastases From LCCC1419

Journal Article Frontiers in Oncology · July 27, 2022 Background: Triple negative breast cancer (TNBC) is an aggressive variant of breast cancer that lacks the expression of estrogen and progesterone receptors (ER and PR) and HER2. Nearly 50% of patients with advanced TNBC will develop brain metastases (BrM), ... Full text Cite

Systemic management of brain metastases in HER2+ breast cancer in 2022.

Journal Article Clin Adv Hematol Oncol · May 2022 Up to half of all patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will eventually acquire brain metastases (BrMs), which are associated with reduced overall survival and decreased quality of life. Although t ... Link to item Cite

HER2-positive breast cancer brain metastasis: A new and exciting landscape.

Journal Article Cancer reports (Hoboken, N.J.) · April 2022 BackgroundBrain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous sys ... Full text Cite

Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer.

Journal Article Journal for immunotherapy of cancer · February 2022 PurposeTriple negative breast cancer (TNBC) is characterized by the presence of immune cells in the tumor microenvironment, however, the response to single-agent immune checkpoint inhibitor (ICI) therapy is modest. Preclinical models have demonstr ... Full text Cite

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma

Journal Article Science Advances · January 21, 2022 About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major ... Full text Cite

Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated With Stereotactic Radiosurgery.

Journal Article Front Oncol · 2022 BACKGROUND: There is a concern that HER2-directed systemic therapies, when administered concurrently with stereotactic radiosurgery (SRS), may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic thera ... Full text Link to item Cite

Advances in the management of breast cancer brain metastases.

Journal Article Neurooncol Adv · November 2021 The development of breast cancer (BC) brain metastases (BrM) is a common complication of advanced disease, occurring in up to half of the patients with advanced disease depending on the subtype. The management of BCBrM requires complex multidisciplinary ca ... Full text Link to item Cite

Silencing of Oncogenic KRAS by Mutant-Selective Small Interfering RNA

Journal Article ACS Pharmacology and Translational Science · April 9, 2021 Oncogenic mutations in the KRAS gene are well-established drivers of cancer. While the recently developed KRASG12C inhibitors offer a targeted KRAS therapy and have shown success in the clinic, KRASG12C represents only 11% of all KRAS mutations. Current th ... Full text Cite

Preparation and characterization of poly(2-oxazoline) micelles for the solubilization and delivery of water insoluble drugs

Journal Article Bio-protocol · March 20, 2021 Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such compounds for cancer therapy, where high doses and intravenous injections are needed (Di et al., 201 ... Full text Cite

Preparation of an orthotopic, syngeneic model of lung adenocarcinoma and the testing of the antitumor efficacy of poly(2-oxazoline) formulation of chemo-and immunotherapeutic agents

Journal Article Bio-protocol · March 20, 2021 Tumor xenograft models developed by transplanting human tissues or cells into immunedeficient mice are widely used to study human cancer response to drug candidates. However, immunedeficient mice are unfit for investigating the effect of immunotherapeutic ... Full text Cite

A Need for More Molecular Profiling in Brain Metastases.

Journal Article Front Oncol · 2021 As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective ... Full text Link to item Cite

A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking.

Journal Article Cancer research · November 2020 Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of ... Full text Cite

Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines.

Journal Article Cancer research · October 2020 Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer, and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due ... Full text Cite

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma.

Journal Article Science advances · June 2020 About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major ... Full text Cite

The Promise of Immunotherapy for Breast Cancer Brain Metastases

Journal Article Current Breast Cancer Reports · December 1, 2019 Purpose of Review: The goal of our review is to describe the rationale for immunotherapy in the treatment of breast cancer brain metastases (BCBM), the current landscape of clinical trials for this disease process, and possible future directions based on a ... Full text Cite

Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes.

Journal Article Nature communications · September 2019 Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, w ... Full text Cite

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

Journal Article Breast cancer research and treatment · October 2018 PurposeHER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated ... Full text Cite

Abstract 2813: Efficacy and pharmacokinetics of niraparib in BRCA-mutant and wild-type intracranial triple negative breast cancer murine models

Conference Cancer Research · July 1, 2018 AbstractIntroduction: Brain metastases arising from triple negative breast cancer (TNBC BM) are common and typically occur in the setting of progressive extracranial metastases. No targeted systemic therapy ... Full text Cite

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer.

Journal Article The Journal of clinical investigation · April 2018 Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate ... Full text Cite

Experimentally Dissecting the Origins of Peroxiredoxin Catalysis.

Journal Article Antioxidants & redox signaling · March 2018 AimsPeroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases involved in oxidant defense and signal transduction. Despite much study, the precise roles of conserved residues remain poorly defined. In this study, we carried out extensive fun ... Full text Cite

Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer.

Journal Article Neuro-oncology · October 2017 BackgroundTriple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Pr ... Full text Cite

Combination therapy with potent PI3K and MAPK inhibitors overcomes adaptive kinome resistance to single agents in preclinical models of glioblastoma.

Journal Article Neuro-oncology · October 2017 BackgroundGlioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI ... Full text Cite

Abstract A03: Several rational combination kinase inhibitor treatments identified by synthetic lethality screens are efficacious in intracranial triple negative breast cancer models

Conference Molecular Cancer Therapeutics · October 1, 2017 AbstractIntroduction: Nearly half of metastatic triple negative breast cancer (TNBC) patients develop brain metastases (BMs) and face a poor prognosis. There are no FDA-approved systemic therapies to treat T ... Full text Cite

LCCC 1025: Phase II study of everolimus, trastuzumab, and vinorelbine for HER2+ breast cancer brain metastases (BCBM).

Conference Journal of Clinical Oncology · May 20, 2017 1011 Background: HER2+ BC is an aggressive subset of BC with high rates of BM and poor survival. Two-thirds of BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy (Rx). This phase II study ... Full text Cite

Multidisciplinary Management of Breast Cancer Brain Metastases.

Journal Article Oncology (Williston Park, N.Y.) · October 2016 This review summarizes the most up-to-date approach to the multidisciplinary management of patients with breast cancer brain metastases. A brief overview of the epidemiology and biology of breast cancer brain metastasis is provided. The perspectives of rad ... Cite

Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT(®) nanoparticle formulation against non-small-cell lung cancer brain metastases.

Journal Article Nanomedicine (London, England) · August 2016 AimParticle Replication in Nonwetting Templates (PRINT(®)) PLGA nanoparticles of docetaxel and acid-labile C2-dimethyl-Si-Docetaxel were evaluated with small molecule docetaxel as treatments for non-small-cell lung cancer brain metastases.Mate ... Full text Cite

Abstract 3867: Combined PI3K and AURKA inhibition are efficacious in triple-negative breast cancer models

Conference Cancer Research · July 15, 2016 AbstractIntroduction: Nearly half of metastatic triple negative breast cancer (TNBC) patients develop brain metastases (BMs) and face a poor prognosis. There are no FDA-approved systemic therapies to treat T ... Full text Cite

Abstract 2579: Combination therapy with MEK inhibition is efficacious in intracranial triple negative breast cancer models

Conference Cancer Research · August 1, 2015 AbstractIntroduction: Nearly half of metastatic triple negative breast cancer (TNBC) patients develop brain metastases (BM) and face a poor prognosis. The blood-brain barrier (BBB) prevents many treatments f ... Full text Cite

Efficacy of Carboplatin Alone and in Combination with ABT888 in Intracranial Murine Models of BRCA-Mutated and BRCA-Wild-Type Triple-Negative Breast Cancer.

Journal Article Molecular cancer therapeutics · April 2015 Patients with breast cancer brain metastases have extremely limited survival and no approved systemic therapeutics. Triple-negative breast cancer (TNBC) commonly metastasizes to the brain and predicts poor prognosis. TNBC frequently harbors BRCA mutations ... Full text Cite

Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice.

Journal Article Food Nutr Res · 2015 BACKGROUND: Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT) or dopamine (DA) in the ce ... Full text Link to item Cite

Abstract 5449A: PI3K and MEK inhibition in intracranial triple negative breast cancer: Efficacy of BKM120 and AZD6244 in preclinical mouse models

Conference Cancer Research · October 1, 2014 AbstractIntroduction: Triple-negative breast cancer (TNBC) is an aggressive subtype which lacks the classical clinical biomarkers for hormone receptors (HR) and HER2. Nearly half of metastatic TNBC patients ... Full text Cite

Breast cancer brain metastases: evidence for neuronal-like adaptation in a 'breast-to-brain' transition?

Journal Article Breast cancer research : BCR · May 2014 Brain metastases remain a significant challenge in the treatment of breast cancer patients due to the unique environment posed by the central nervous system. A better understanding of the biology of breast cancer cells that have metastasized to the brain i ... Full text Cite

Dietary manipulation of serotonergic and dopaminergic function in C57BL/6J mice with amino acid depletion mixtures.

Journal Article J Neural Transm (Vienna) · February 2014 Amino acid (AA) depletion techniques have been used to decrease serotonin (5-HT) and/or dopamine (DA) synthesis after administration of a tryptophan (acute tryptophan depletion, ATD) or phenylalanine/tyrosine-free (phenylalanine-tyrosine depletion, PTD) AA ... Full text Link to item Cite

Estradiol replacement enhances cocaine-stimulated locomotion in female C57BL/6 mice through estrogen receptor alpha.

Journal Article Neuropharmacology · September 2013 Psychostimulant effects are enhanced by ovarian hormones in women and female rodents. Estradiol increases behavioral responses to psychostimulants in women and female rats, although the underlying mechanism is unknown. This study utilized mice to investiga ... Full text Link to item Cite

Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice.

Journal Article Psychopharmacology (Berl) · February 2013 RATIONALE: Women are more sensitive than men to psychostimulants and progress from initial use to drug addiction more quickly. The mouse has been an under-utilized model to study sex differences in psychostimulant action. Mice could serve as an ideal genet ... Full text Link to item Cite

Individual differences in psychostimulant responses of female rats are associated with ovarian hormones and dopamine neuroanatomy.

Journal Article Neuropharmacology · June 2012 Ovarian hormones modulate the pharmacological effects of psychostimulants and may enhance vulnerability to drug addiction. Female rats have more midbrain dopamine neurons than males and greater dopamine uptake and release rates. Cocaine stimulates motor be ... Full text Link to item Cite

Effects of acute tryptophan depletion on brain serotonin function and concentrations of dopamine and norepinephrine in C57BL/6J and BALB/cJ mice.

Journal Article PLoS One · 2012 Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subse ... Full text Link to item Cite

Androgen decreases dopamine neurone survival in rat midbrain.

Journal Article J Neuroendocrinol · April 2010 Clinical studies show that men are more likely to develop disorders affecting midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease (PD). Although a great deal of focus has been given to the role of oestrogen in the maintenance of ... Full text Link to item Cite

Oestrogen receptors enhance dopamine neurone survival in rat midbrain.

Journal Article J Neuroendocrinol · April 2010 Previous findings in our laboratory and elsewhere have shown that ovariectomy of rats in adulthood attenuates cocaine-stimulated locomotor behaviour. Ovarian hormones enhance both cocaine-stimulated behaviour and increase dopamine overflow after psychomoto ... Full text Link to item Cite

Autophagy provides nutrients but can lead to Chop-dependent induction of Bim to sensitize growth factor-deprived cells to apoptosis.

Journal Article Mol Biol Cell · February 2009 Tissue homeostasis is controlled by the availability of growth factors, which sustain exogenous nutrient uptake and prevent apoptosis. Although autophagy can provide an alternate intracellular nutrient source to support essential basal metabolism of apopto ... Full text Link to item Cite