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HER2+ metastatic breast cancer

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https://www.readbyqxmd.com/read/29784737/nccn-guidelines-updates-breast-cancer
#1
Sharon H Giordano, Anthony D Elias, William J Gradishar
The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor-positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29781326/progression-free-survival-with-endocrine-based-therapies-following-progression-on-non-steroidal-aromatase-inhibitor-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-a-network-meta-analysis
#2
Rajeev Ayyagari, Derek Tang, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, David Chandiwana, Anand A Dalal, Polly Ann Niravath
OBJECTIVE: To quantify the comparative efficacy of currently available endocrine-based therapies (ETs) for postmenopausal women with HR+/HER2- mBC after NSAI progression. DESIGN: network meta-analysis (NMA) Methods: Randomized clinical trials of ETs for HR+/HER2- mBC were identified via a systematic literature review using Medline, EMBASE, Cochrane Library, and key conference proceedings. All trials met the following inclusion criteria: 1) included women with HR+/HER2- mBC, 2) previous treatment with ETs or chemotherapy as first-line therapy, 3) treatment with ET as monotherapy or in combination with targeted therapy, 4) PFS was reported, and 5) published in 2007 (when HER2 testing became standardized) or later...
May 21, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29781317/combination-therapies-for-the-treatment-of-her2-positive-breast-cancer-current-and-future-prospects
#3
Mariana Brandão, Noam F Pondé, Francesca Poggio, Nuria Kotecki, Mauren Salis, Matteo Lambertini, Evandro de Azambuja
HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1 and neratinib, alone or combined in "dual HER2-blockade" regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity and cost-effectiveness...
May 21, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29779938/expression-of-truncated-her2-and-its-prognostic-value-in-her2-positive-breast-cancer-patients
#4
Alaa Mohamed Maria, Mohamed El-Shebiney, Ayman Mohamed El-Saka, Yomna Zamzam
PURPOSE: The purpose of this work was to assess the truncated form of human epidermal growth factor receptor 2 (HER2) such as p95-HER2 expression in HER2-positive breast cancer (BC) patients who developed metastatic disease after adjuvant treatment with a trastuzumab-containing regimen. PATIENTS AND METHODS: Thirty-two histologically diagnosed HER2-positive BC patients who developed distant failure after treatment with trastuzumab-based chemotherapy (CT) regimen as an adjuvant therapy were included in the study...
May 17, 2018: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/29778787/efficacy-of-palbociclib-combinations-in-hormone-receptor-positive-metastatic-breast-cancer-patients-after-prior-everolimus-treatment
#5
Ajay Dhakal, Christina M Matthews, Ellis Glenn Levine, Kilian Elizabeth Salerno, Fan Zhang, Kazuaki Takabe, Amy P Early, Stephen B Edge, Tracy O'Connor, Thaer Khoury, Jessica S Young, Mateusz Opyrchal
PURPOSE: Outcome data on hormone receptor positive (HR+ ), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2- ) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+ HER2- MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+ HER2- MBC with prior exposure to everolimus while receiving palbociclib-based therapy...
April 28, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29777404/randomized-trial-comparing-resection-of-primary-tumor-with-no-surgery-in-stage-iv-breast-cancer-at-presentation-protocol-mf07-01
#6
Atilla Soran, Vahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Muslumanoglu, Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel, Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Betül Bozkurt, Ali Uzunkoy, Neset Koksal, Bahadir M Gulluoglu, Bulent Unal, Can Atalay, Emin Yıldırım, Ergun Erdem, Semra Salimoglu, Atakan Sezer, Ayhan Koyuncu, Gunay Gurleyik, Haluk Alagol, Nalan Ulufi, Uğur Berberoglu, Mustafa Dulger, Omer Cengiz, Efe Sezgin, Ronald Johnson
BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group...
May 17, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29777007/development-of-64-cu-nota-trastuzumab-for-her2-targeting-radiopharmaceutical-with-improved-pharmacokinetics-for-human-study
#7
Sang-Keun Woo, Su Jin Jang, Min-Jung Seo, Ju Hui Park, Byoung Soo Kim, Eun Jung Kim, Yong Jin Lee, Tae Sup Lee, Gwang Il An, In Ho Song, Youngho Seo, Kwang Il Kim, Joo Hyun Kang
Purpose The purpose of this study was to develop 64 Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2. Methods Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64 Cu. Serum stability and immunoreactivity of 64 Cu-NOTA-trastuzumab were tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer xenograft model (BT-474). Internal dosimetry of experimental animals was performed using the image-based approach with the Monte Carlo N-Particle Code...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29774130/targeting-invadopodia-mediated-breast-cancer-metastasis-by-using-abl-kinase-inhibitors
#8
Tomer Meirson, Alessandro Genna, Nikola Lukic, Tetiana Makhnii, Joel Alter, Ved P Sharma, Yarong Wang, Abraham O Samson, John S Condeelis, Hava Gil-Henn
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769179/rna-profiles-of-circulating-tumor-cells-and-extracellular-vesicles-for-therapy-stratification-of-metastatic-breast-cancer-patients
#9
Corinna Keup, Pawel Mach, Bahriye Aktas, Mitra Tewes, Hans-Christian Kolberg, Siegfried Hauch, Markus Sprenger-Haussels, Rainer Kimmig, Sabine Kasimir-Bauer
BACKGROUND: Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS: Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points...
May 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29766409/where-youth-matters-clinicopathologic-characteristics-and-emerging-trends-in-treatment-and-outcomes-in-young-irish-women-with-breast-cancer
#10
Megan Greally, Jennifer Kielty, Geoffrey A Watson, Geoffrey Das, Christina Malouf, Lynda McSorley, Niamh Coleman, Cecily Quinn, Enda W McDermott, Giuseppe Gullo, John Crown, Ruth S Prichard, Catherine M Kelly, Janice M Walshe
BACKGROUND: Young women with breast cancer (YWBC) represent 7-12% of breast cancer diagnoses and ostensibly have more biologically aggressive subtypes with higher relapse and mortality rates. We studied the clinical and pathological characteristics in YWBC and examined how outcomes and treatment have evolved. METHODS: YWBC were identified from pathology databases at two tertiary centers. Patients were divided into two cohorts: those diagnosed from 2000 to 2005 (C1) and from 2006 to 2015 (C2)...
May 15, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29766363/palbociclib-in-highly-pretreated-metastatic-er-positive-her2-negative-breast-cancer
#11
G Hoste, K Punie, H Wildiers, B Beuselinck, I Lefever, E Van Nieuwenhuysen, S N Han, P Berteloot, N Concin, R Salihi, I Vergote, P Neven
PURPOSE: We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). METHODS: Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment...
May 16, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29765249/is-progression-free-survival-a-more-relevant-endpoint-than-overall-survival-in-first-line-hr-her2-metastatic-breast-cancer
#12
Anna Forsythe, David Chandiwana, Janina Barth, Marroon Thabane, Johan Baeck, Anastasiya Shor, Gabriel Tremblay
Background: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2- MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29765247/progression-free-survival-time-to-progression-as-a-potential-surrogate-for-overall-survival-in-hr-her2-metastatic-breast-cancer
#13
Anna Forsythe, David Chandiwana, Janina Barth, Marroon Thabane, Johan Baeck, Gabriel Tremblay
Background: Several recent randomized controlled trials (RCTs) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) have demonstrated significant improvements in progression-free survival (PFS); however, few have reported improvement in overall survival (OS). The surrogacy of PFS or time to progression (TTP) for OS has not been formally investigated in HR+, HER2- MBC. Methods: A systematic literature review of RCTs in HR+, HER2- MBC was conducted to identify studies that reported both median PFS/TTP and OS...
2018: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29763896/evaluation-of-the-her2-and-hormone-receptor-status-in-metastatic-breast-cancer-using-cell-blocks-a-multi-institutional-study
#14
Rieko Nishimura, Yuya Murata, Kiyoshi Mori, Katsushige Yamashiro, Kazuya Kuraoka, Shu Ichihara, Kenichi Taguchi, Hiroyoshi Suzuki, Masahiro Ito, Natsumi Yamashita
OBJECTIVE: We explore the problems associated with the cell block (CB) method for receptor analysis in breast cancer metastases and propose a method for reporting the results. STUDY DESIGN: Nine institutions used the CB method for the analysis of hormone receptors (HRs) and HER2 (human epidermal growth factor receptor 2) protein in cytological specimens of breast cancer metastases in routine practice. The stained slides were independently evaluated by 8 pathologists...
May 15, 2018: Acta Cytologica
https://www.readbyqxmd.com/read/29763779/clinical-implications-of-the-non-luminal-intrinsic-subtypes-in-hormone-receptor-positive-breast-cancer
#15
REVIEW
Juan Miguel Cejalvo, Tomás Pascual, Aranzazu Fernández-Martínez, Fara Brasó-Maristany, Roger R Gomis, Charles M Perou, Montserrat Muñoz, Aleix Prat
Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched [HER2-E] and Basal-like) have been identified and intensively studied. In this article, we review and discuss the clinical implications of the 2 non-luminal subtypes (i.e. HER2-E and Basal-like) identified within hormone receptor (HR)-positive disease. After reviewing 32 studies for a total of 13,091 samples, ∼8% and ∼ 15% of early and metastatic HR+/HER2-negative breast cancer, respectively, were found to be non-luminal...
May 7, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29755676/genetic-heterogeneity-and-actionable-mutations-in-her2-positive-primary-breast-cancers-and-their-brain-metastases
#16
Leticia De Mattos-Arruda, Charlotte K Y Ng, Salvatore Piscuoglio, Maria Gonzalez-Cao, Raymond S Lim, Maria R De Filippo, Nicola Fusco, Anne M Schultheis, Carolina Ortiz, Santiago Viteri, Alexandra Arias, Gabriel S Macedo, Mafalda Oliveira, Patricia Gomez, Cristina Teixidó, Paolo Nuciforo, Vicente Peg, Cristina Saura, Santiago Ramon Y Cajal, Francesc Tresserra Casas, Britta Weigelt, Javier Cortes, Joan Seoane, Jorge S Reis-Filho
Brain metastases constitute a challenge in the management of patients with HER2-positive breast cancer treated with anti-HER2 systemic therapies. Here we sought to define the repertoire of mutations private to or enriched for in HER2-positive brain metastases. Massively parallel sequencing targeting all exons of 254 genes frequently mutated in breast cancers and/or related to DNA repair was used to characterize the spatial and temporal heterogeneity of HER2-positive breast cancers and their brain metastases in six patients...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753961/the-role-of-parp-inhibition-in-triple-negative-breast-cancer-unraveling-the-wide-spectrum-of-synthetic-lethality
#17
REVIEW
Marios Papadimitriou, Giannis Mountzios, Christos A Papadimitriou
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3 years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12 months...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29751334/treatment-of-advanced-her2-positive-breast-cancer-2018-and-beyond
#18
REVIEW
Noam Pondé, Mariana Brandão, Georges El-Hachem, Emilie Werbrouck, Martine Piccart
In the 1980s the importance of HER2 signalling to the aberrant behaviour of a subset of breast cancer cells was recognized for the first time and, consequently, a hitherto unknown subtype of breast cancer - HER2-positive (HER2+) breast cancer was identified. The development of the anti-HER2 class of drugs, first with trastuzumab, followed closely by lapatinib, pertuzumab, and T-DM1, has improved outcomes dramatically. Nevertheless, metastatic HER2+ breast cancer remains an incurable disease and new therapeutic options are needed...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29744813/assessment-of-the-methods-used-to-detect-her2-positive-advanced-extramammary-paget-s-disease
#19
Ikuko Hirai, Keiji Tanese, Yoshio Nakamura, Atsushi Otsuka, Yasuhiro Fujisawa, Yuki Yamamoto, Hiroo Hata, Taku Fujimura, Shigeto Matsushita, Koji Yoshino, Kaori Kameyama, Masayuki Amagai, Takeru Funakoshi
The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget's disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH...
May 9, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29743141/chemotherapy-patient-with-stevens-johnson-syndrome-presents-to-the-emergency-department-a-case-report
#20
Stephanie Widmer, Michele Grossman
BACKGROUND: Stevens-Johnson syndrome (SJS) is part of a continuum of severe mucocutaneous reactions, commonly thought to be triggered by certain medications. The syndrome itself is characterized by diffuse necrosis and detachment of the epidermis. CASE REPORT: This case report discusses a patient who presented to the Emergency Department with signs and symptoms of Stevens-Johnson syndrome four days after chemotherapy administration of ribociclib (Kisqali®). Ribociclib is a newly approved, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor indicated for the treatment of hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer...
April 11, 2018: American Journal of Emergency Medicine
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