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https://www.readbyqxmd.com/read/27920624/neoadjuvant-chemotherapy-with-docetaxel-carboplatin-and-weekly-trastuzumab-is-active-in-her2-positive-early-breast-cancer-results-after-a-median-follow-up-of-over-4-years
#1
Hans-Christian Kolberg, Leyla Akpolat-Basci, Miltiades Stephanou, Bahriye Aktas, Carla Verena Hannig, Cornelia Liedtke
INTRODUCTION: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#2
REVIEW
Guowei Gu, Derek Dustin, Suzanne Aw Fuqua
In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting...
November 21, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27866067/escalating-and-de-escalating-treatment-in-her2-positive-early-breast-cancer
#3
REVIEW
Heikki Joensuu
The current standard adjuvant systemic treatment of early HER2-positive breast cancer consists of chemotherapy plus 12months of trastuzumab, with or without endocrine therapy. Several trials have investigated modifications of the standard treatment that are shorter and less resource-demanding (de-escalation) or regimens that aim at dual HER2 inhibition or include longer than 12months of HER2-targeted treatment (escalation). Seven randomized trials investigate shorter than 12months of trastuzumab treatment duration...
November 10, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27861156/an-nk-cell-line-hank-expressing-high-levels-of-granzyme-and-engineered-to-express-the-high-affinity-cd16-allele
#4
Caroline Jochems, James W Hodge, Massimo Fantini, Rika Fujii, Y Maurice Morillon Ii, John W Greiner, Michelle R Padget, Sarah R Tritsch, Kwong Yok Tsang, Kerry S Campbell, Hans Klingemann, Laurent Boissel, Shahrooz Rabizadeh, Patrick Soon-Shiong, Jeffrey Schlom
Natural killer (NK) cells are known to play a role in mediating innate immunity, in enhancing adaptive immune responses, and have been implicated in mediating anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by reactivity of CD16 with the Fc region of human IgG1 antibodies. The NK-92 cell line, derived from a lymphoma patient, has previously been well characterized and adoptive transfer of irradiated NK-92 cells has demonstrated safety and shown preliminary evidence of clinical benefit in cancer patients...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831502/dual-her2-blockade-with-pertuzumab-and-trastuzumab-in-her2-positive-early-breast-cancer-a-subanalysis-of-data-from-the-randomized-phase-iii-geparsepto-trial
#5
S Loibl, C Jackisch, A Schneeweiss, S Schmatloch, B Aktas, C Denkert, H Wiebringhaus, S Kümmel, M Warm, S Paepke, M Just, C Hanusch, J Hackmann, J-U Blohmer, M Clemens, S Dan Costa, B Gerber, K Engels, V Nekljudova, G von Minckwitz, M Untch
BACKGROUND: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n=396) in comparison to the HER2- cohort...
November 9, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27813707/development-and-preclinical-studies-of-64-cu-nota-pertuzumab-f-ab-2-for-imaging-changes-in-tumor-her2-expression-associated-with-response-to-trastuzumab-by-pet-ct
#6
Karen Lam, Conrad Chan, Raymond M Reilly
We previously reported that microSPECT/CT imaging with (111)In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')2 of pertuzumab modified with NOTA chelators for complexing (64)Cu. The effect of the administered mass (5-200 µg) of (64)Cu-NOTA-pertuzumab F(ab')2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts...
November 4, 2016: MAbs
https://www.readbyqxmd.com/read/27781258/-research-status-quo-and-progression-in-targeted-therapy-for-advanced-gastric-cancer
#7
Rui Feng, Xiaotian Zhang, Sheng Yang
With the deeper research of the proliferation, invasion and metastasis mechanisms of the gastric cancer, targeted therapy has become a hot spot in this field. The exploration of targeted agents for gastric cancer is mainly concentrated upon the drugs that target human epidermal growth factor receptor (HER) family, the vascular endothelial growth factor (VEGF), the phosphatidylinositol 3-kinase-protein kinase/mammalian target of rapamycin (PI3K/mTOR) and the NF-κB signaling pathways. The targeted drugs relevant to HER family include the Cetuximab, Nimotuzumab, Matuzumab, Panitumumab and Erlotinib which are aimed at HER-1, the Trastuzumab, Pertuzumab and T-DM1 (trastuzumab emtansine) which are aimed at HER-2, and the Lapatinib and Afatinib which are the multi-target agents of HER...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27766079/restoring-lost-anti-her-2-th1-immunity-in-breast-cancer-a-crucial-role-for-th1-cytokines-in-therapy-and-prevention
#8
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27760931/-the-role-of-preoperative-chemotherapy-depending-on-breast-cancer-subtype
#9
Naoki Hayashi, Madoka Iwase, Tomohiro Ochi, Akina Seki, Naoko Matsuda, Hideko Yamauchi
Following the discovery that the prognostic impact of preoperative chemotherapy depends on the primary breast cancer subtype, the treatment strategy for primary breast cancer changed. Pathologic complete response(pCR)with preoperative chemotherapy is predictive of a favorable prognosis in patients with HER2 type or triple-negative type breast cancer, but not in patients with ER-positive/HER2-negative, the so-called Luminal type, breast cancer. However, the role of preoperative chemotherapy in patients with Luminal-B type breast cancer who may need chemotherapy should be further assessed...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27713176/a-functional-signal-profiling-test-for-identifying-a-subset-of-her2-negative-breast-cancers-with-abnormally-amplified-her2-signaling-activity
#10
Yao Huang, David J Burns, Benjamin E Rich, Ian A MacNeil, Abhijit Dandapat, Sajjad M Soltani, Samantha Myhre, Brian F Sullivan, Leo T Furcht, Carol A Lange, Sara A Hurvitz, Lance G Laing
The results of clinical trials evaluating the efficacy of HER2 inhibitors in patients with breast cancer indicate that the correlation between HER2 receptor levels and patient outcomes is as low as 50%. The relatively weak correlation between HER2 status and response to HER2-targeting drugs suggests that measurement of HER2 signaling activity, rather than absolute HER2 levels, may more accurately diagnose HER2-driven breast cancer. A new diagnostic test, the CELx HER2 Signaling Profile (CELx HSP) test, is demonstrated to measure real-time HER2 signaling function in live primary cells...
October 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713148/a-novel-mechanism-of-action-of-her2-targeted-immunotherapy-is-explained-by-inhibition-of-nrf2-function-in-ovarian-cancer-cells
#11
Hilal S Khalil, Simon P Langdon, Alexey Goltsov, Tero Soininen, David J Harrison, James Bown, Yusuf Y Deeni
Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27692565/halt-d-a-phase-ii-evaluation-of-crofelemer-for-the-prevention-and-prophylaxis-of-diarrhea-in-patients-with-breast-cancer-on-pertuzumab-based-regimens
#12
Jennifer J Gao, Ming Tan, Paula R Pohlmann, Sandra M Swain
Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer will develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are frequently used to treat CID after diarrhea occurs, but neither is used prophylactically or targets the underlying mechanism. Previous studies suggest blocking epidermal growth factor receptor may cause excess chloride secretion, resulting in diarrhea. Crofelemer is derived from the red latex of the Croton lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator and calcium-activated chloride channels, and is U...
August 27, 2016: Clinical Breast Cancer
https://www.readbyqxmd.com/read/27683008/appendicitis-caused-by-the-metastasis-of-her2-positive-breast-cancer
#13
Ryutaro Mori, Manabu Futamura, Kasumi Morimitsu, Kazuhiro Yoshida
The appropriate therapy for metastatic breast cancer must be selected based on the immunohistochemical phenotype of the cancer. However, biopsy for metastatic lesions is difficult. We herein report a patient with incidental appendicitis caused by a metastatic breast cancer which was successfully treated with effective therapy chosen based on the pathological diagnosis obtained on resection. The patient was a 56-year-old female with right breast cancer and an immunohistochemical status of estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2 (HER2) (3+), and Ki67 40 %...
December 2016: Surgical Case Reports
https://www.readbyqxmd.com/read/27675495/acute-toxicity-in-patients-with-her2-positive-breast-cancer-treated-with-adjuvant-radiation-therapy-and-concurrent-trastuzumab-and-pertuzumab
#14
D Spiegel, P K Marcom, B Peterson, J Force, L Howie, M Palta, R C Blitzblau, J K Horton
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27675061/her-family-blockade-in-head-and-neck-squamous-cell-carcinoma-couple-therapy-efficacy-of-cetuximab-and-pertuzumab-combined-with-photon-irradiation
#15
J B Guy, B Méry, C Rancoule, A Vallard, S Espenel, A S Wozny, S Simonet, D Bernard, D Ardail, M Beuve, G Alphonse, C Rodriguez-Lafrasse, N Magné
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27632289/use-of-a-multiplexed-immunoassay-pro-onc-assay-to-detect-her2-abnormalities-in-circulating-tumor-cells-of-women-with-her2-negative-metastatic-breast-cancer-lack-of-response-to-her2-targeted-therapy
#16
John D Hainsworth, Patrick B Murphy, Jose R Alemar, Brooke R Daniel, Robyn R Young, Denise A Yardley
PURPOSE: Determination of HER2 status by testing circulating tumor cells (CTCs), compared to sampling tumor biopsies, may improve patient management by allowing ongoing assessment of HER2 status during the disease course. The PRO Onc assay (Prometheus Laboratories; San Diego, CA) is a multiplexed immunoassay that measures the expression and activation of HER2 in CTCs. In this study, we screened patients with metastatic HER2-negative breast cancer with the PRO Onc assay; patients with HER2 overexpression or activation received a trial of HER2-targeted therapy...
November 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27628552/-a-case-of-her2-positive-inflammatory-breast-cancer-for-which-preoperative-chemotherapy-with-pertuzumab-resulted-in-a-pathological-complete-response
#17
Naomi Konishi, Takao Iwanaga, Yoshito Ishino, Aya Sugisawa, Shozo Ide, Hiroko Kimura, Takashi Iwata, Hideki Watanabe, Takeshi Yokoe, Eiki Ojima, Hideki Ito, Tetsuya Ikeda, Hitoshi Tonouchi, Chika Shigemori
A 52-year-old woman presented with redness and swelling with a peau d'orange appearance in the whole right breast. Ultrasound revealed elevated subcutaneus fat density and a diffuse hypoechoic area. She was diagnosed with inflammatory breast cancer(T4dN2M0, Stage III B of the HER2 subtype). After 4 courses of EC treatment as primary systemic therapy, the hypoechoic area was still present. Subsequent chemotherapy with pertuzumab, trastuzumab, and docetaxel was effective, as hypoechoic area was not observed on ultrasound...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27628551/-a-case-of-luminal-her2-advanced-breast-cancer-with-liver-metastasis-showed-pathological-complete-response-to-the-therapy-with-pertuzumab-plus-trastuzumab-plus-docetaxel
#18
Asako Hamaoka, Takayuki Matsuda, Eiichi Konishi, Tetsuya Taguchi
A 56-year-old woman noticed a mass on her left breast and visited our hospital. An irregular mass of 3 cm with associated axillary lymphadenopathy was detected under the nipple of the left breast. After further evaluations, the diagnosis was an invasive ductal carcinoma(scirrhous carcinoma)ofLuminal -HER2 type with liver metastases(cT4bN1M1, Stage IV). Treatment was initiated with a combination ofpertuzumab, trastuzumab, and docetaxel(PTD). The primary tumor showed a clinical complete response, and the liver metastases and the axillary lymph node metastases showed a partial response...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27618787/her2-her3-dimer-quantification-by-flim-fret-predicts-breast-cancer-metastatic-relapse-independently-of-her2-ihc-status
#19
Gregory Weitsman, Paul R Barber, Lan K Nguyen, Katherine Lawler, Gargi Patel, Natalie Woodman, Muireann T Kelleher, Sarah E Pinder, Mark Rowley, Paul A Ellis, Anand D Purushotham, Anthonius C Coolen, Boris N Kholodenko, Borivoj Vojnovic, Cheryl Gillett, Tony Ng
Overexpression of HER2 is an important prognostic marker, and the only predictive biomarker of response to HER2-targeted therapies in invasive breast cancer. HER2-HER3 dimer has been shown to drive proliferation and tumor progression, and targeting of this dimer with pertuzumab alongside chemotherapy and trastuzumab, has shown significant clinical utility. The purpose of this study was to accurately quantify HER2-HER3 dimerisation in formalin fixed paraffin embedded (FFPE) breast cancer tissue as a novel prognostic biomarker...
July 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27564098/an-anti-erbb2-fully-human-antibody-circumvents-trastuzumab-resistance
#20
Qiong Lu, Lingfei Wang, Yajun Zhang, Xiaojie Yu, Chao Wang, Huajing Wang, Yang Yang, Xiaodan Chong, Tian Xia, Yanchun Meng, Yuxiao Wang, Cuihua Lu, Lijun Zhou, Bohua Li
Trastuzumab, an anti-HER2/ErbB2 humanized antibody, has shown great clinical benefits in ErbB2-positive breast cancer treatment. Despite of its effectiveness, response rate to trastuzumab is limited and resistance is common. Here, we developed a new anti-ErbB2 antibody, denoted as H2-18, which was isolated from a phage display human antibody library. Previous studies have demonstrated that trastuzumab recognizes the juxtamembrane region of domain IV, and pertuzumab, another humanized ErbB2-specific antibody, binds to ErbB2 near the center of domain II...
August 24, 2016: Oncotarget
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