Medicine and Health Sciences Commons^™

Stay On Track: A Pilot Randomized Control Trial On The Feasibility Of A Diet And Exercise Intervention In Patients With Breast Cancer Receiving Radiotherapy, Gopika Senthilkumar, Aronne M Schottstaedt, Lindsay L Peterson, Lauren N Pedersen, Christopher R Chitambar, Alexis Vistocky, Anjishnu Banerjee, John M Longo, Tracy Kelly, Adam Currey, Melinda R Stolley, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy.

EXPERIMENTAL DESIGN: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations. The control group (n = 22) was administered a diet/exercise information binder. All patients received a Fitbit, and at …

Preexisting Diabetes And Breast Cancer Treatment Among Low-Income Women, Bayu Begashaw Bekele, Min Lian, Chester Schmaltz, Tracy Greever-Rice, Pratibha Shrestha, Ying Liu

2020-Current year OA Pubs

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain.

OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023.

EXPOSURE: Preexisting …

Cellular Geometry And Epithelial-Mesenchymal Plasticity Intersect With Piezo1 In Breast Cancer Cells, Choon Leng So, Mélanie Robitaille, Francisco Sadras, Michael H Mccullough, Michael J G Milevskiy, Geoffrey J Goodhill, Sarah J Roberts-Thomson, Gregory R Monteith

2020-Current year OA Pubs

Differences in shape can be a distinguishing feature between different cell types, but the shape of a cell can also be dynamic. Changes in cell shape are critical when cancer cells escape from the primary tumor and undergo major morphological changes that allow them to squeeze between endothelial cells, enter the vasculature, and metastasize to other areas of the body. A shift from rounded to spindly cellular geometry is a consequence of epithelial-mesenchymal plasticity, which is also associated with changes in gene expression, increased invasiveness, and therapeutic resistance. However, the consequences and functional impacts of cell shape changes and the …

Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng

2020-Current year OA Pubs

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence …

Induction Of Viral Mimicry Upon Loss Of Dhx9 And Adar1 In Breast Cancer Cells, Kyle A Cottrell, Sua Ryu, Jackson R Pierce, Luisangely Soto Torres, Holly E Bohlin, Angela M Schab, Jason D Weber

2020-Current year OA Pubs

UNLABELLED: Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The IFN-inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for adenosine deaminase acting on RNA 1 (ADAR1) in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110-interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in …

Neighborhood Disadvantage And Breast Cancer-Specific Survival In The Us, Neha Goel, Alexandra E Hernandez, Angela Mazul

2020-Current year OA Pubs

IMPORTANCE: Despite improvements in breast cancer screening, treatment, and survival, disparate breast cancer-specific survival outcomes persist, particularly in disadvantaged neighborhoods. Most of these disparities are attributed to disparities in individual, tumor, and treatment characteristics. However, a critical knowledge gap exists as to whether disparities in breast cancer-specific survival remain after accounting for individual, tumor, and treatment characteristics.

OBJECTIVE: To evaluate if neighborhood disadvantage is associated with shorter breast cancer-specific survival after controlling for individual, tumor, and treatment characteristics in a national population.

DESIGN, SETTING, AND PARTICIPANTS: This national retrospective cohort study included patients with breast cancer diagnosed from 2013 to …

Hepsin Promotes Breast Tumor Growth Signaling Via The Tgfβ-Egfr Axis, Denis Belitškin, Pauliina Munne, Shishir M Pant, Johanna M Anttila, Ilida Suleymanova, Kati Belitškina, Daniel Kirchhofer, James Janetka, Taivo Käsper, Sami Jalil, Jeroen Pouwels, Topi A Tervonen, Juha Klefström

2020-Current year OA Pubs

Hepsin, a type II transmembrane serine protease, is commonly overexpressed in prostate and breast cancer. The hepsin protein is stabilized by the Ras-MAPK pathway, and, downstream, this protease regulates the degradation of extracellular matrix components and activates growth factor pathways, such as the hepatocyte growth factor (HGF) and transforming growth factor beta (TGFβ) pathway. However, how exactly active hepsin promotes cell proliferation machinery to sustain tumor growth is not fully understood. Here, we show that genetic deletion of the gene encoding hepsin (Hpn) in a WAP-Myc model of aggressive MYC-driven breast cancer inhibits tumor growth in the primary syngrafted sites …

Low Rna Disruption During Neoadjuvant Chemotherapy Predicts Pathologic Complete Response Absence In Patients With Breast Cancer, Marina Elena Cazzaniga, Foluso Ademuyiwa, Et Al.

2020-Current year OA Pubs

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in …

Breast Cancer Incidence Among Us Women Aged 20 To 49 Years By Race, Stage, And Hormone Receptor Status, Shuai Xu, Sara Murtagh, Yunan Han, Fei Wan, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Breast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known.

OBJECTIVE: To evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from Surveillance, Epidemiology, and End Results …

Pectoral Muscle Removal In Mammogram Images: A Novel Approach For Improved Accuracy And Efficiency, Simin Chen, Debbie L Bennett, Graham A Colditz, Shu Jiang

2020-Current year OA Pubs

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra).

METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast …

Lasofoxifene Versus Fulvestrant For Er+/Her2- Metastatic Breast Cancer With An Esr1 Mutation: Results From The Randomized, Phase Ii Elaine 1 Trial, M P Goetz, N A Bagegni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts.

PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, …

Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz

2020-Current year OA Pubs

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk.

METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the …

Lipidome Of Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.

METHODS: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon …

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.

2020-Current year OA Pubs

UNLABELLED: Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF …

Interplay Between Esr1/Pik3ca Codon Variants, Oncogenic Pathway Alterations And Clinical Phenotype In Patients With Metastatic Breast Cancer (Mbc): Comprehensive Circulating Tumor Dna (Ctdna) Analysis, Lorenzo Gerratana, Andrew A Davis, Katherine Clifton, Whitney L Hensing, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.

METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among …

Neratinib + Fulvestrant + Trastuzumab For Hr-Positive, Her2-Negative, Her2-Mutant Metastatic Breast Cancer: Outcomes And Biomarker Analysis From The Summit Trial, K Jhaveri, H Park, C Ma, R Bose, L Peterson, Et Al.

2020-Current year OA Pubs

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.

PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + …

Association And Prediction Utilizing Craniocaudal And Mediolateral Oblique View Digital Mammography And Long-Term Breast Cancer Risk, Simin Chen, Rulla M Tamimi, Graham A Colditz, Shu Jiang

2020-Current year OA Pubs

UNLABELLED: Mammographic percentage of volumetric density is an important risk factor for breast cancer. Epidemiology studies historically used film images often limited to craniocaudal (CC) views to estimate area-based breast density. More recent studies using digital mammography images typically use the averaged density between craniocaudal (CC) and mediolateral oblique (MLO) view mammography for 5- and 10-year risk prediction. The performance in using either and both mammogram views has not been well-investigated. We use 3,804 full-field digital mammograms from the Joanne Knight Breast Health Cohort (294 incident cases and 657 controls), to quantity the association between volumetric percentage of density extracted …

Examination Of Fully Automated Mammographic Density Measures Using Libra And Breast Cancer Risk In A Cohort Of 21,000 Non-Hispanic White Women, Laurel A Habel, Aimilia Gastounioti, Et Al.

2020-Current year OA Pubs

BACKGROUND: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding.

METHODS: We conducted a cohort study among 21,150 non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were 40-74 years at enrollment, followed for up to 10 years, and had archived …

Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan

2020-Current year OA Pubs

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition …

Upregulation Of The Oct3/4 Network In Basal Breast Cancer Is Associated With Its Metastatic Potential And Shows Tissue Dependent Variability, Robin G Rajan, Raisa I Krutilina, Tatyana N Ignatova, Zoran S Pavicevich, Galina M Dulatova, Maria A Lane, Arindam R Chatterjee, Robert J Rooney, Mymoon Antony, Vivian R Hagerty, Nickolay V Kukekov, Khalid A Hanafy, Frank D Vrionis

2020-Current year OA Pubs

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the

Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.

EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome …

Identifying Regions Of Interest In Mammogram Images, Shu Jiang, Jiguo Cao, Graham A. Colditz

2020-Current year OA Pubs

Screening mammography is the primary preventive strategy for early detection of breast cancer and an essential input to breast cancer risk prediction and application of prevention/risk management guidelines. Identifying regions of interest within mammogram images that are associated with 5- or 10-year breast cancer risk is therefore clinically meaningful. The problem is complicated by the irregular boundary issue posed by the semi-circular domain of the breast area within mammograms. Accommodating the irregular domain is especially crucial when identifying regions of interest, as the true signal comes only from the semi-circular domain of the breast region, and noise elsewhere. We address …

Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased …

Circadian Rhythm Disrupting Behaviours And Cancer Outcomes In Breast Cancer Survivors: A Systematic Review, Kelly D'Cunha, Yikyung Park, Melinda M Protani, Marina M Reeves

2020-Current year OA Pubs

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer.

METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast …

Design Of Serena-6, A Phase Iii Switching Trial Of Camizestrant In Esr1-Mutant Breast Cancer During First-Line Treatment, Nicholas Turner, Cynthia Huang-Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, Cynthia X Ma, Erica L Mayer, Yeon Hee Park, Steven Fox, Xiaochun Liu, Sasha Mcclain, Francois-Clement Bidard

2020-Current year OA Pubs

No abstract provided.

Impact Of The Covid-19 Pandemic On Breast, Colorectal, Lung, And Prostate Cancer Stage At Diagnosis According To Race, Jennifer Berrian, Ying Liu, Nkiruka Ezenwajiaku, Alvaro Moreno-Aspitia, Sara J Holton, Adetunji T Toriola, Graham A Colditz, Ashley J Housten, Lannis Hall, Mark A Fiala, Foluso O Ademuyiwa

2020-Current year OA Pubs

PURPOSE: To determine if the COVID-19 pandemic has further exacerbated racial disparities in late-stage presentation of breast, colorectal, lung, and prostate cancers.

METHODS: We conducted a registry-based retrospective study of patients with newly reported diagnoses of breast, colorectal, lung, and prostate cancers between March 2019-June 2019 (pre-COVID-19) and March 2020-June 2020 (early-COVID-19). We compared the volume of new diagnoses and stage at presentation according to race between both periods.

RESULTS: During the study period, a total of 3528 patients had newly diagnosed cancer; 3304 of which had known disease stages and were included in the formal analyses. 467 (14.1%) were …

Antitumour Activity Of Neratinib In Patients With Her2-Mutant Advanced Biliary Tract Cancers, James J Harding, Haeseong Park, Et Al.

2020-Current year OA Pubs

HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has activity in HER2-mutant tumours. SUMMIT is an open-label, single-arm, multi-cohort, phase 2, 'basket' trial of neratinib in patients with solid tumours harbouring oncogenic HER2 somatic mutations (ClinicalTrials.gov: NCT01953926). The primary objective of the BTC cohort, which is now complete, is first objective response rate (ORR) to neratinib 240 mg orally daily. Secondary objectives include confirmed ORR, clinical benefit rate, progression-free survival, duration of response, overall survival, safety and tolerability. Genomic analyses were exploratory. …

Final Findings From The Control Trial: Strategies To Reduce The Incidence And Severity Of Neratinib-Associated Diarrhea In Patients With Her2-Positive Early-Stage Breast Cancer, Arlene Chan, Ron Bose, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies.

METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks …

A Cdh3-Β-Catenin-Laminin Signaling Axis In A Subset Of Breast Tumor Leader Cells Control Leader Cell Polarization And Directional Collective Migration, Priscilla Y Hwang, Jairaj Mathur, Yanyang Cao, Jose Almeida, Jiayu Ye, Vasilios Morikis, Daphne Cornish, Maria Clarke, Sheila A Stewart, Amit Pathak, Gregory D Longmore

2020-Current year OA Pubs

Carcinoma dissemination can occur when heterogeneous tumor and tumor-stromal cell clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system mimicking native breast tumor microenvironment, we developed 3D computational models, which hypothesize that leader cells need to generate high protrusive forces and overcome extracellular matrix (ECM) resistance at the leading edge. From single-cell sequencing analyses, we find that leader cells are heterogeneous and identify and isolate …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …