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HER2+ metastatic breast cancer

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https://www.readbyqxmd.com/read/27904779/generation-characterization-and-maintenance-of-trastuzumab-resistant-her2-breast-cancer-cell-lines
#1
Sandra Zazo, Paula González-Alonso, Ester Martín-Aparicio, Cristina Chamizo, Ion Cristóbal, Oriol Arpí, Ana Rovira, Joan Albanell, Pilar Eroles, Ana Lluch, Juan Madoz-Gúrpide, Federico Rojo
Trastuzumab became the therapy of choice for patients with HER2-positive breast cancer in 1998, and it has provided clinical benefit ever since. However, a significant percentage of patients show primary resistance to trastuzumab at diagnosis, and most patients with metastatic disease that initially respond to trastuzumab eventually progress (acquired resistance). Consequently, there is an urgent need to improve our knowledge of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27900589/intrinsic-her2-v777l-mutation-mediates-resistance-to-trastuzumab-in-a-breast-cancer-patient
#2
Yosuke Hirotsu, Hiroshi Nakagomi, Kenji Amemiya, Toshio Oyama, Masayuki Inoue, Hitoshi Mochizuki, Masao Omata
HER2 (ERBB2) is an oncogene and 20% of breast cancers display HER2 amplification. The HER2 monoclonal antibody, trastuzumab, is used to treat breast cancers that display HER2 amplification, with good responses in 80-90% of cases; however, 10% of tumours develop resistance to trastuzumab. In this study, we collected data of primary breast cancer patients who treated at hospital during 2004-2014. In our cohort, 205 of 1497 primary breast cancer patients showed HER2-amplification, and 20 experienced recurrence after trastuzumab therapy...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27895501/a-fish-based-method-for-assessment-of-her-2-amplification-status-in-breast-cancer-circulating-tumor-cells-following-cellsearch-isolation
#3
Henrik Frithiof, Kristina Aaltonen, Lisa Rydén
INTRODUCTION: Amplification of the HER-2/neu (HER-2) proto-oncogene occurs in 10%-15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting growth of cancer cells. Tumor classification is determined in primary tumor tissue and metastatic biopsies. However, malignant cells tend to alter their phenotype during disease progression. Circulating tumor cell (CTC) analysis may serve as an alternative to repeated biopsies. The Food and Drug Administration-approved CellSearch system allows determination of the HER-2 protein, but not of the HER-2 gene...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27889595/is-there-a-role-for-salvage-radiotherapy-in-locally-advanced-breast-cancer-refractory-to-neoadjuvant-chemotherapy
#4
R C Coelho, F M L Da Silva, I M L Do Carmo, B V Bonaccorsi, S M Hahn, L D Faroni
INTRODUCTION: Locally advanced breast cancer (LABC) is a major problem, especially in developing countries. The standard treatment for LABC is neoadjuvant chemotherapy, with or without anti-Her2 therapy, followed by surgery, radiotherapy, and adjuvant systemic treatment if appropriate. However, there are few data in the literature addressing alternatives when neoadjuvant chemotherapy fails to reduce the tumour for surgery. MATERIALS AND METHODS: We conducted a retrospective study including all patients who had non-metastatic LABC treated with neoadjuvant chemotherapy and who were not eligible for surgical resection; these patients were submitted to salvage radiotherapy (RTX) between January 2000 and December 2012 at the Brazilian National Cancer Institute...
November 24, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27885435/comparison-of-immunophenotypes-of-primary-breast-carcinomas-and-multiple-corresponding-distant-metastases-an-autopsy-study-of-25-patients
#5
B Szekely, Zs I Nagy, Zs Farago, O Kiss, G Lotz, K A Kovacs, L Madaras, N Udvarhelyi, M Dank, Gy Szentmartoni, Zs Baranyai, L Harsanyi, A M Tőkés, Jozsef Timar, A M Szasz, J Kulka
Phenotypical change in metastatic breast carcinoma has widely been accepted as an inherent biological feature rather than technical fault. We analyzed the immunohistochemical phenotype and histopathological features of 25 primary breast carcinomas and 90 corresponding distant metastases in 23 organs retrospectively. Histological slides were reviewed for prognostic and predictive factors. Overall, metastases were more similar to each other and often differed from the primary tumor. We created a 3-step grouping system based on the localization of metastases...
November 24, 2016: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#6
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/27876131/chemosensitization-role-of-fulvestrant-in-combination-with-chemotherapy-in-postmenopausal-hormone-receptor-positive-and-human-epidermal-growth-factor-negative-metastatic-breast-cancer
#7
Qing-Qing Luo, Vishnu Prasad Adhikari, Chun-Xia Zhao, He Wu, Wei Dai, Xin Li, Yu-Tuan Wu, Kai-Nan Wu, Ling-Quan Kong
In metastatic breast cancer (MBC), hormone receptor positive (HR+), human epidermal growth factor negative (HER2-) subtype accounts for the majority. With various new modalities available to prolong life span in this group of patients, the effect is distant from optimum. Prevalent strategy of treating postmenopausal HR+ HER2- MBC is application of chemotherapy (CT) after progression of disease on endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients and CT works better with HR- tumor cells...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27865536/breast-cancer
#8
REVIEW
Nadia Harbeck, Michael Gnant
Breast cancer is one of the three most common cancers worldwide. Early breast cancer is considered potentially curable. Therapy has progressed substantially over the past years with a reduction in therapy intensity, both for locoregional and systemic therapy; avoiding overtreatment but also undertreatment has become a major focus. Therapy concepts follow a curative intent and need to be decided in a multidisciplinary setting, taking molecular subtype and locoregional tumour load into account. Primary conventional surgery is not the optimal choice for all patients any more...
November 16, 2016: Lancet
https://www.readbyqxmd.com/read/27861874/a-real-world-multicentre-retrospective-study-of-paclitaxel-bevacizumab-and-maintenance-therapy-as-first-line-for-her2-negative-metastatic-breast-cancer
#9
Teresa Gamucci, Lucia Mentuccia, Clara Natoli, Isabella Sperduti, Alessandra Cassano, Andrea Michelotti, Luigi Di Lauro, Domenico Sergi, Alessandra Fabi, Maria G Sarobba, Paolo Marchetti, Maddalena Barba, Emanuela Magnolfi, Marcello Maugeri-Saccà, Ernesto Rossi, Valentina Sini, Antonino Grassadonia, Domenica Pellegrini, Antonino Astone, Cecilia Nisticò, Franco Angelini, Angela Vaccaro, Arianna Pellegrino, Claudia De Angelis, Michela Palleschi, Luca Moscetti, Ilaria Bertolini, Simonetta Buglioni, Antonio Giordano, Laura Pizzuti, Patrizia Vici
Bevacizumab in combination with taxanes in HER2-negative metastatic breast cancer (MBC) patients has shown improved progression-free survival (PFS), despite the lack of clear overall survival (OS) benefit. We performed a retrospective analysis to evaluate the impact of paclitaxel-bevacizumab and of maintenance therapy with bevacizumab (BM) and endocrine therapy (ET) in the real-world practice. We identified 314 HER2-negative MBC patients treated in 12 cancer centers. Overall, the median PFS and OS were 14 and 40 months, respectively...
November 11, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27853985/a-definition-for-aggressive-disease-in-patients-with-her-2-negative-metastatic-breast-cancer-an-expert-consensus-of-the-spanish-society-of-medical-oncology-seom
#10
REVIEW
A González, A Lluch, E Aba, J Albanell, A Antón, I Álvarez, F Ayala, A Barnadas, L Calvo, E Ciruelos, J Cortés, J de la Haba, J M López-Vega, E Martínez, M Muñoz, I Peláez, A Redondo, Á Rodríguez, C A Rodríguez, A Ruíz, A Llombart
PURPOSE: To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. METHODS: A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement...
November 16, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27851873/mri-surveillance-of-cancer-cell-fate-in-a-brain-metastasis-model-after-early-radiotherapy
#11
Donna H Murrell, Niloufar Zarghami, Michael D Jensen, Fiona Dickson, Ann F Chambers, Eugene Wong, Paula J Foster
PURPOSE: Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy...
November 14, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27847222/use-of-maintenance-endocrine-therapy-after-chemotherapy-in-metastatic-breast-cancer
#12
REVIEW
S Sutherland, D Miles, A Makris
BACKGROUND: For women with oestrogen receptor+ metastatic breast cancer (MBC), the options for systemic treatment include endocrine therapy (ET) and chemotherapy. For women whose disease is also HER2+, anti-HER2 therapies are also routinely used either with chemotherapy or less commonly with ET. Where chemotherapy is used as initial therapy, treatment is often discontinued due to cumulative toxicity in the absence of disease progression. In this setting, there is the option of introducing ET with the aim of prolonging response and delaying relapse...
November 12, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27843957/whether-her2-positive-non-breast-cancers-are-candidates-for-treatment-with-ado-trastuzumab-emtansine
#13
REVIEW
Azadeh Moghaddas, Ali Borhani
The National Comprehensive Cancer Network (NCCN) has recommended Ado-trastuzumab emtansine (T-DM1) as a preferred agent for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer and prior trastuzumab therapy. Overexpression of HER2 was reported in other cancer types such as bladder, gastric and urogenital carcinosarcomas similar to what is discovered in breast cancer. Some preclinical studies demonstrated the potential anti-tumor effects of T-DM1 in HER2-positive non-breast cancers...
October 2016: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/27831505/research-needs-in-breast-cancer
#14
REVIEW
F Cardoso, N Harbeck, C H Barrios, J Bergh, J Cortés, N El Saghir, P A Francis, C A Hudis, S Ohno, A H Partridge, G W Sledge, I E Smith, K A Gelmon
New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: 1) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; 2) explore optimal adjuvant treatment durations; 3) develop better tools and strategies to identify patients with genetic predisposition; 4) improve care in young patients with breast cancer; 5) develop tools to speed up drug development in biomarker-defined populations; 6) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; 7) evaluate the efficacy of local-regional treatments for metastatic disease; 8) better define the optimal sequence of treatments in the metastatic setting; 9) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); 10) better understand the biology and identify new targets in triple-negative breast cancer; 11) better understand immune surveillance in breast cancer and further develop immunotherapies; and 12) increase survivorship research efforts including supportive care and quality of life...
November 9, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27829202/more-than-just-the-median-calculating-survival-times-for-patients-with-her2-positive-metastatic-breast-cancer-using-data-from-recent-randomised-trials
#15
A Vasista, M R Stockler, T West, N Wilcken, B E Kiely
OBJECTIVES: To estimate worst-case, typical and best-case scenarios for survival as a communication aid for managing patients with HER2-positive metastatic breast cancer (MBC) starting HER2-targeted therapies. METHODS: We sought randomised trials of HER2-targeted therapies and recorded the following percentiles (representative scenarios) from each OS curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We then tested whether we could estimate these percentiles for each OS curve by multiplying its median by four simple multiples: 0...
November 6, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27817944/bevacizumab-plus-paclitaxel-versus-placebo-plus-paclitaxel-as-first-line-therapy-for-her2-negative-metastatic-breast-cancer-meridian-a-double-blind-placebo-controlled-randomised-phase-iii-trial-with-prospective-biomarker-evaluation
#16
David Miles, David Cameron, Igor Bondarenko, Lyudmila Manzyuk, Juan Carlos Alcedo, Roberto Ivan Lopez, Seock-Ah Im, Jean-Luc Canon, Yaroslav Shparyk, Denise A Yardley, Norikazu Masuda, Jungsil Ro, Neelima Denduluri, Stanislas Hubeaux, Cheng Quah, Carlos Bais, Joyce O'Shaughnessy
AIM: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). METHODS: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m(2) on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal...
November 4, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27813128/preparation-and-preclinical-evaluation-of-131-i-trastuzumab-for-breast-cancer
#17
Mythili Kameswaran, Vikram Gota, Rajwardhan Ambade, Sudeep Gupta, Ashutosh Dash
Trastuzumab that targets the human epidermal growth factor receptor type 2 (HER2) is known to benefit patients with HER2+ metastatic breast cancer. The objective was to explore the potential of (131) I-trastuzumab for treatment of breast cancers. Radioiodination of trastuzumab was carried out by chloramine-T method, purified by using PD-10 column, and characterized by size exclusion high-performance liquid chromatography on a gel column. In vitro studies were carried out in HER2+ cells to determine the specificity of the radioimmunoconjugate...
November 4, 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27813061/development-of-lu-177-trastuzumab-for-radioimmunotherapy-of-her2-expressing-breast-cancer-and-its-feasibility-assessment-in-breast-cancer-patients
#18
Priya Bhusari, Rakhee Vatsa, Gurpreet Singh, Madan Parmar, Amanjit Bal, Devinder K Dhawan, Bhagwant R Mittal, Jaya Shukla
HER2/neu is over expressed in 20-25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed...
November 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27812689/association-of-polymorphisms-in-fcgr2a-and-fcgr3a-with-degree-of-trastuzumab-benefit-in-the-adjuvant-treatment-of-erbb2-her2-positive-breast-cancer-analysis-of-the-nsabp-b-31-trial
#19
Patrick G Gavin, Nan Song, S Rim Kim, Corey Lipchik, Nicole L Johnson, Hanna Bandos, Melanie Finnigan, Priya Rastogi, Louis Fehrenbacher, Eleftherios P Mamounas, Sandra M Swain, D Lawrence Wickerham, Charles E Geyer, Jong-Hyeon Jeong, Joseph P Costantino, Norman Wolmark, Soonmyung Paik, Kay L Pogue-Geile
Importance: Preclinical models and studies in the metastatic and neoadjuvant settings suggest that single nucleotide polymorphisms in FCGR3A and FCGR2A may be associated with differential response to trastuzumab in the treatment of ERBB2/HER2-positive breast cancer, by modulating antibody-dependent cell-mediated cytotoxic effects. Objective: To evaluate the effect of FCGR2A and FCGR3A polymorphisms on trastuzumab efficacy in the adjuvant treatment of ERBB2/HER2-positive breast cancer...
November 3, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27810861/ribociclib-lengthens-breast-cancer-survival
#20
(no author information available yet)
The combination of antiestrogen therapy and ribociclib, an investigational CDK4/6 inhibitor, led to improved outcomes in women with metastatic HR-positive, HER2-negative breast cancer, according to findings presented at a meeting of the European Society for Medical Oncology. The combination significantly increased progression-free survival compared with letrozole alone in a large phase III trial-data that could lead to FDA approval.
November 3, 2016: Cancer Discovery
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