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HER2+ Breast Cancer

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https://www.readbyqxmd.com/read/29452759/feasibility-study-of-weekly-nanoparticle-albumin-bound-paclitaxel-150-mg-m-2-followed-by-fluorouracil-epirubicin-and-cyclophosphamide-therapy-as-neoadjuvant-chemotherapy-for-her2-negative-breast-cancer
#1
Yasuyuki Kojima, Hisanori Kawamoto, Toru Nishikawa, Ryosuke Hayami, Arata Shimo, Ei Haku, Kyoko Akiyama, Koichiro Tsugawa
BACKGROUND: Although several studies have shown efficacy of nanoparticle albumin-bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-three patients with no previous chemotherapy were enrolled to receive nab-paclitaxel 150 mg/m 2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment...
January 11, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29452382/simulated-ablation-for-detection-of-cells-impacting-paracrine-signalling-in-histology-analysis
#2
Jake P Taylor-King, Etienne Baratchart, Andrew Dhawan, Elizabeth A Coker, Inga Hansine Rye, Hege Russnes, S Jon Chapman, David Basanta, Andriy Marusyk
Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and hampers the efficiency of anti-cancer therapies. Dealing with this cellular heterogeneity requires adequate understanding of its sources, which is extremely difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational differences with the dynamic responses to microenvironmental cues. The later comes in form of both direct physical interactions, as well as inputs from gradients of secreted signalling molecules. Furthermore, tumour cells can not only receive microenvironmental cues, but also produce them...
February 14, 2018: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/29450494/comparison-of-the-performance-of-6-prognostic-signatures-for-estrogen-receptor-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#3
Ivana Sestak, Richard Buus, Jack Cuzick, Peter Dubsky, Ralf Kronenwett, Carsten Denkert, Sean Ferree, Dennis Sgroi, Catherine Schnabel, Frederick L Baehner, Elizabeth Mallon, Mitch Dowsett
Importance: Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. Objective: To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years. Design, Setting, and Participants: This retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)-negative breast cancer...
February 15, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29449694/interaction-between-stat3-and-gli1-tgli1-oncogenic-transcription-factors-promotes-the-aggressiveness-of-triple-negative-breast-cancers-and-her2-enriched-breast-cancer
#4
Sherona R Sirkisoon, Richard L Carpenter, Tadas Rimkus, Ashley Anderson, Alexandria Harrison, Allison M Lange, Guangxu Jin, Kounosuke Watabe, Hui-Wen Lo
Signal transducer and activator of transcription 3 (STAT3), glioma oncogene homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1 isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1 has not been explored. To address this knowledge gap, we analyzed 47 node-positive breast cancer specimens using immunohistochemical staining and found that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%) breast carcinomas, and in lymph node metastases (65%)...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29448628/functionalized-magnetic-plga-nanospheres-for-targeting-and-bioimaging-of-breast-cancer
#5
Seung-Jun Lee, Hee-Jin Kim, Yong-Min Huh, Il Won Kim, Jae Hyun Jeong, Jin-Chul Kim, Jong-Duk Kim
Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers...
March 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29448311/enhancing-decision-making-about-adjuvant-chemotherapy-in-early-breast-cancer-following-endopredict-testing
#6
Lesley Fallowfield, Lucy Matthews, Shirley May, Valerie Jenkins, David Bloomfield
Chemotherapy side-effects can be substantial. There is increasing recognition that some oestrogen receptor positive (ER+ve), human epidermal growth factor receptor 2 negative (HER2-ve) patients with breast cancer derive no benefit from chemotherapy and experience only iatrogenic harm. Gene expression profiling tests help refine recurrence risk and likely chemotherapy benefit. EndoPredict® is one such test, which classifies risks of distant recurrence as low or high in patients treated with surgery and adjuvant endocrine therapy alone...
February 15, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29448072/a-phase-iii-study-comparing-sb3-a-proposed-trastuzumab-biosimilar-and-trastuzumab-reference-product-in-her2-positive-early-breast-cancer-treated-with-neoadjuvant-adjuvant-treatment-final-safety-immunogenicity-and-survival-results
#7
X Pivot, I Bondarenko, Z Nowecki, M Dvorkin, E Trishkina, J-H Ahn, S-A Im, T Sarosiek, S Chatterjee, M Z Wojtukiewicz, Y Shparyk, V Moiseyenko, M Bello, V Semiglazov, Y Lee, J Lim
BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide)...
February 12, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29445928/efficacy-and-safety-of-trastuzumab-lapatinib-and-paclitaxel-neoadjuvant-treatment-with-or-without-prolonged-exposure-to-anti-her2-therapy-and-with-or-without-hormone-therapy-for-her2-positive-primary-breast-cancer-a-randomised-five-arm-multicentre-open-label
#8
N Masuda, M Toi, N Yamamoto, H Iwata, K Kuroi, H Bando, S Ohtani, T Takano, K Inoue, Y Yanagita, H Kasai, S Morita, T Sakurai, S Ohno
BACKGROUND: Dual blockade of HER2 promises increased pathological complete response (pCR) rate compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. Many questions remain regarding optimal duration of treatment and combination impact of endocrine therapy for luminal HER2 disease. METHODS: We designed a randomised phase II, five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs...
February 14, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29445299/choosing-wisely-after-publication-of-level-i-evidence-in-breast-cancer-radiotherapy
#9
Joshua R Niska, Sameer R Keole, Barbara A Pockaj, Michele Y Halyard, Samir H Patel, Donald W Northfelt, Richard J Gray, Nabil Wasif, Carlos E Vargas, William W Wong
Background: Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT...
2018: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29445216/evaluation-of-her2-specific-peptide-ligand-for-its-employment-as-radiolabeled-imaging-probe
#10
Hadis Honarvar, Enrica Calce, Nunzianna Doti, Emma Langella, Anna Orlova, Jos Buijs, Valentina D'Amato, Roberto Bianco, Michele Saviano, Vladimir Tolmachev, Stefania De Luca
HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444670/breast-cancer-in-ethiopia-evidence-for-geographic-difference-in-the-distribution-of-molecular-subtypes-in-africa
#11
Endale Hadgu, Daniel Seifu, Wondemagegnhu Tigneh, Yonas Bokretsion, Abebe Bekele, Markos Abebe, Thomas Sollie, Sofia D Merajver, Christina Karlsson, Mats G Karlsson
BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2)...
February 14, 2018: BMC Women's Health
https://www.readbyqxmd.com/read/29441705/injectable-tough-alginate-cryogels-as-cancer-vaccines
#12
Ting-Yu Shih, Serena O Blacklow, Aileen W Li, Benjamin R Freedman, Sidi Bencherif, Sandeep T Koshy, Max C Darnell, David J Mooney
A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection...
February 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29440915/effects-of-core-needle-biopsy-and-subsequent-neoadjuvant-chemotherapy-on-molecular-alterations-and-outcome-in-breast-cancer
#13
Lingmin Xie, Xiaolei Li, Qinchuan Wang, Jichun Zhou, Jun Shen, Lixi Luo, Yi Lu, Linbo Wang
Objectives: The aim of our study is to evaluate the effect of core needle biopsy (CNB) and subsequent neoadjuvant chemotherapy (NAC) on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth hormone receptor 2 (HER2) and Ki67 in breast cancer, and the associated influencing factors. Materials and methods: In this retrospective cohort study, 143 patients with primary operable breast cancer who received NAC were included. ER, PR, HER2 and Ki67 statuses were compared between pretreatment and posttreatment residual samples...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29440297/mi130004-a-novel-antibody-drug-conjugate-combining-trastuzumab-with-a-molecule-of-marine-origin-shows-outstanding-in-vivo-activity-against-her2-expressing-tumors
#14
Pablo M Aviles, Juan Manuel Dominguez, María José Guillén-Navarro, Maria Jose Muñoz-Alonso, Cristina Mateo, Raquel Rodriguez-Acebes, Jose Manuel Molina-Guijarro, Andrés Francesch, Juan Fernando Martínez-Leal, Simon Munt, Carlos M Galmarini, Carmen Cuevas
In the search for novel payloads to design new antibody-drug conjugates (ADCs), marine compounds represent an interesting opportunity given their unique chemical features. PM050489 is a marine compound that binds β-tubulin at a new site and disrupts the microtubule network hence leading to mitotic aberrations and cell death. PM050489 has been conjugated to trastuzumab via Cys residues through a non-cleavable linker and the resulting ADC, named MI130004, has been studied. Analysis of MI130004 delivered data consistent with the presence of two molecules of PM050489 per antibody molecule, likely bound to both sides of the intermolecular disulfide bond connecting the antibody light and heavy chains...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29440181/a-first-in-human-study-of-the-new-oral-selective-estrogen-receptor-degrader-azd9496-for-hr-her2-advanced-breast-cancer
#15
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P O Lindemann, Shethah Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
PURPOSE: AZD9496 is an oral non-steroidal, small-molecule inhibitor of estrogen receptor alpha (ERα), and a potent and selective antagonist and degrader of ERα. This first in human Phase 1 study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity. EXPERIMENTAL DESIGN: Forty-five patients received AZD9496 (20 mg once daily to 600 mg twice daily) in a dose-escalation, dose- expansion 'rolling 6' design...
February 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439457/immune-landscape-of-breast-cancers
#16
REVIEW
Divya Nagarajan, Stephanie E B McArdle
Breast cancer is a very heterogeneous disease, both at a molecular and a histological level. Five intrinsic subtypes were initially identified-Luminal-A, Luminal-B, HER2⁺, Triple negative/basal like (TNBC) and normal like-subsequently expanded to seven (Basal-like-1 and 2, mesenchymal, mesenchymal stem-like, luminal androgen receptor, immuno-modulatory and unstable). Although genetic and epigenetic changes are key pathogenic events, the immune system plays a substantial role in promoting progression and metastasis...
February 11, 2018: Biomedicines
https://www.readbyqxmd.com/read/29438745/an-automated-epifluorescence-microscopy-imaging-assay-for-the-identification-of-phospho-akt-level-modulators-in-breast-cancer-cells
#17
Elke Kaemmerer, Dane Turner, Amelia A Peters, Sarah J Roberts-Thomson, Gregory R Monteith
AKT is an enzyme of the PI3K/pAKT pathway, regulating proliferation and cell survival. High basal levels of active, phosphorylated AKT (pAKT) are associated with tumor progression and therapeutic resistance in some breast cancer subtypes, including HER2 positive breast cancers. Various stimuli can increase pAKT levels and elevated basal pAKT levels are a feature of PTEN-deficient breast cancer cell lines. The aim of this study was to develop an assay able to identify modulators of pAKT levels using an automated epifluorescence microscope and high content analysis...
February 10, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29437899/prognostic-value-and-clinicopathological-significance-of-serum-and-tissue-based-cytokeratin-18-express-level-in-breast-cancer-a-meta-analysis
#18
Jiangling Yang, Sicheng Gao, Jian Xu, Junfeng Zhu
Cytokeratin 18 (CK18), a type Ⅰ cytokeratin of the intermediate filament family, has been associated with the prognosis of cancer patients for decades. However, its exact role in predicting the clinical outcome of breast cancer remains controversial. To comprehensively investigated the prognostic value of CK18 in breast cancer, a systematically meta-analysis was conducted to explore the association between CK18 expression and overall survival. Literature collection was conducted by retrieving electronic databases Pubmed, Cochrane Library, Web of Science, EMBASE and OVID completely (up to January 1, 2017)...
February 5, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29437794/drug-resistance-in-her2-positive-breast-cancer-brain-metastases-blame-the-barrier-or-the-brain
#19
Sheheryar Kabraji, Jing Ni, Nancy Lin, Shaozhen Xie, Eric P Winer, Jean J Zhao
The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBMs) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and in vivo models suggest that inadequate drug penetration across the 'blood-tumor' barrier is not the whole story. Using HER2-positive breast cancer brain metastases as a case study, we highlight recent data from orthotopic brain metastasis models that implicates brain-specific drug resistance mechanisms in BCBMs and suggests a translational research paradigm to guide drug development for treatment of BCBMs...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29437768/fda-approval-ribociclib-for-the-treatment-of-postmenopausal-women-with-hormone-receptor-positive-her2-negative-advanced-or-metastatic-breast-cancer
#20
Anand Shah, Erik Bloomquist, Shenghui Tang, Wentao Fu, Youwei Bi, Qi Liu, Jingyu Yu, Ping Zhao, Todd R Palmby, Kirsten B Goldberg, C J George Chang, Paresma Patel, Elleni Alebachew, Amy Tilley, William F Pierce, Amna Ibrahim, Gideon M Blumenthal, Rajeshwari Sridhara, Julia A Beaver, Richard Pazdur
On March 13, 2017, the U.S. Food and Drug Administration approved ribociclib (KISQALI, Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2)...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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