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HER2+ metastatic breast cancer

Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Ji-Yeon Kim, Jin-Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Background/Aims: We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. Methods: We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016)...
March 16, 2018: Korean Journal of Internal Medicine
Jeff Sperinde, Weidong Huang, Aki Vehtari, Ahmed Chenna, Pirkko-Liisa Kellokumpu-Lehtinen, John Winslow, Petri Bono, Yolanda Lie, Christos J Petropoulos, Jodi Marie Weidler, Heikki Joensuu
PURPOSE: Expression of p95HER2 (p95), a truncated form of the HER2 receptor, which lacks the trastuzumab binding site but retains kinase activity, has been reported as a prognostic biomarker for poor outcomes in trastuzumab-treated HER2-positive metastatic breast cancer. The impact of p95 expression on trastuzumab treatment efficacy in early HER2-positive breast cancer is less clear. In the current study, p95 was tested as a predictive marker of trastuzumab treatment benefit in the HER2-positive subset of the FinHer adjuvant phase III trial...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Saranya Chumsri, Jeff Sperinde, Heshan Liu, Joseph Gligorov, Jean-Philippe Spano, Martine Antoine, Alvaro Moreno-Aspita, Winston Tan, John Winslow, Christos J Petropoulos, Ahmed Chenna, Michael Bates, Jodi Marie Weidler, Weidong Huang, Amylou C Dueck, Edith A Perez
BACKGROUND: p95HER2 is a truncated form of human epidermal growth factor receptor 2 (HER2) that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials. METHODS: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elena Ongaro, Lorenzo Gerratana, Marika Cinausero, Giacomo Pelizzari, Elena Poletto, Manuela Giangreco, Claudia Andreetta, Stefano Pizzolitto, Carla Di Loreto, Alessandro Marco Minisini, Mauro Mansutti, Stefania Russo, Gianpiero Fasola, Fabio Puglisi
AIM: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. METHODS: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test...
March 12, 2018: Future Oncology
Leticia Varella, Jame Abraham, Megan Kruse
Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF) that interferes with VEGF binding to its receptor on vascular endothelium. Bevacizumab has been approved for the treatment of various malignant tumors, and has been studied in combination with several cytotoxic agents in the treatment of breast cancer. In 2008, the US Food and Drug Administration granted accelerated approval for the use of bevacizumab in combination with weekly paclitaxel for first-line treatment of HER2-negative metastatic breast cancer...
August 2017: Seminars in Oncology
Kimberly Blackwell, Joseph Gligorov, Ira Jacobs, Chris Twelves
Trastuzumab improves survival outcomes for patients with HER2-positive (HER2+ ) breast cancer, yet not all such women receive this important therapy. Trastuzumab was approved by the US Food and Drug Administration in 1998 and the European Medicines Agency in 2000 as treatment for HER2+ metastatic breast cancer (MBC). Observational studies between 2000 and 2015 in patients with HER2+ MBC suggest that nearly 12% in the United States, 27% to 54% in Europe, and 27.1% to 49.2% in China did not receive trastuzumab or any other HER2-targeted agent as first- and/or later-line for treatment of metastatic disease...
February 2, 2018: Clinical Breast Cancer
Misato Okazaki, Yoshiya Horimoto, Masahiko Tanabe, Yuko Ichikawa, Emi Tokuda, Atsushi Arakawa, Toshiyuki Kobayashi, Mitsue Saito
Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer...
March 8, 2018: Medical Oncology
P S Blanchette, D N Desautels, G R Pond, J M S Bartlett, S Nofech-Mozes, M J Yaffe, K I Pritchard
PURPOSE: We have limited capability to predict survival among patients treated for metastatic HER2-positive breast cancer. Further research is warranted to identify significant prognostic and predictive factors. METHODS: We identified all HER2-positive metastatic breast cancer patients receiving trastuzumab at the Sunnybrook Odette Cancer Centre (SOCC) from 1999 to 2013 through the Cancer Care Ontario (CCO) Registry (n = 256) and selected patients with available pathology reports (n = 154)...
March 8, 2018: Breast Cancer Research and Treatment
Chhanda Bose, Sanjay Awasthi, Rajendra Sharma, Helen Beneš, Martin Hauer-Jensen, Marjan Boerma, Sharda P Singh
Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known...
2018: PloS One
Luc Cabel, Alina Fuerea, Ludovic Lacroix, Capucine Baldini, Patricia Martin, Antoine Hollebecque, Sophie Postel-Vinay, Andrea Varga, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Jean Yves Scoazec, Samy Ammari, Fabrice André, Jean-Charles Soria, Christophe Massard, Loic Verlingue
A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2- altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification...
February 9, 2018: Oncotarget
John Syrios, Evelina Pappa, Nikolaos Volakakis, Anastasios Grivas, John Alafis, Sofia Manioudaki, Vasiliki Tzouda, Athanasios Korogiannos, Cleopatra Rapti, Nektarios Koufopoulos, Adamantia Nikolaidou, Eleftheria Kanavou, Athanasios Alexopoulos, Anna Koumarianou
Purpose: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (anti-HER2) antibody delivered intravenously, has revolutionized the treatment of patients with breast cancer overexpressing HER2 protein. Recently, a newer subcutaneous formulation was shown to have comparable efficacy to the initial intravenous trastuzumab. In this study, we aimed to evaluate the impact of subcutaneous trastuzumab on the health-related quality of life (HRQoL) of patients diagnosed with early or metastatic HER2-overexpressing breast cancer...
2018: Breast Cancer: Basic and Clinical Research
Zhenying Chen, Fangmeng Fu, Fang Li, Zhaohui Zhu, Yinghong Yang, Xiangjin Chen, Bing Jia, Shan Zheng, Chao Huang, Weibing Miao
PURPOSE: This study aimed to investigate the value of99m technetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([99m Tc]3PRGD2 ) imaging in diagnosis and staging of breast cancer compared with 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG) imaging, and to explore the expression of integrin αv β3 in tumor vascular endothelial cells. PROCEDURES: Forty-two women with suspected breast cancer underwent both [99m Tc]3PRGD2 imaging and [18 F]FDG imaging...
March 1, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Diaddin Hamdan, François Darrouzain, Theodora Bejan-Angoulvant, Charles Isorni, Laurent Zelek, Gilles Paintaud, Anne Janin, Guilhem Bousquet
PURPOSE: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule...
March 1, 2018: Cancer Chemotherapy and Pharmacology
Silvia Paola Corona, Daniele Generali
Although early breast cancer (BC) is highly curable, advanced or metastatic disease poses numerous challenges in terms of medical management and treatment decisions and is associated with significantly worse prognosis. Among the new targeted agents, anticancer drugs exploiting the cell-cycle machinery have shown great potential in preclinical studies. CDK4/6 inhibitors target the cyclin D/CDK/retinoblastoma signaling pathway, inducing cell-cycle arrest, reduced cell viability and tumor shrinking. As the cyclin D/CDK complex is activated downstream of estrogen signaling, the combination of CDK4/6 inhibitors with standard endocrine therapies represents a rational approach to elicit synergic antitumor activity in hormone receptor-positive BC...
2018: Drug Design, Development and Therapy
Alexandre Perrier, Joseph Gligorov, Guillaume Lefèvre, Mathieu Boissan
Breast cancer is a major health problem worldwide. In ~15% of breast cancers, the epidermal growth factor receptor HER2, a transmembrane protein, is overexpressed. This HER2 overexpression is associated with an aggressive form of the disease and a poor clinical prognosis. The extracellular domain (ECD) of HER2 is released into the blood by a proteolytic mechanism known as "ECD shedding". This proteolytic shedding leaves a constitutively active truncated receptor in the membrane that is 10-100-fold more oncogenic than the full-length receptor and promotes the growth and survival of cancer cells...
February 28, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Amélie Darlix, Gaia Griguolo, Simon Thezenas, Eva Kantelhardt, Christoph Thomssen, Maria Vittoria Dieci, Federica Miglietta, PierFranco Conte, Antoine Laurent Braccini, Jean Marc Ferrero, Caroline Bailleux, William Jacot, Valentina Guarneri
Breast cancer (BC) metastatic behavior varies according to the hormone receptors (HR) and HER2 statuses. Indeed, patients with triple-negative (TN) and HER2+ tumors are at higher risk of brain metastases (BM). The objective of this multinational cohort was to evaluate BM kinetics depending on the BC subtype. We retrospectively analyzed a series of BC patients with BM diagnosed in four European institutions (1996-2016). The delay between BC and BM diagnoses (BM-free survival) according to tumor biology was estimated with the Kaplan-Meier method...
February 27, 2018: Journal of Neuro-oncology
Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmen Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone
BACKGROUND: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. METHODS: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer...
February 23, 2018: Lancet Oncology
Abeer Ismail, Rehab El-Awady, Ghada Mohamed, Marwa Hussein, Shimaa Shwaki Ramadan
Objective: To determine the frequency and prognostic significance of vitamin D deficiency in Egyptian women with breast cancer (BC). Methods: This prospective study included 50 women with primary invasive, non-metastatic BC. The serum level of 25-hydroxy vitamin D [25(OH)D was measured by ELISA at diagnosis, before any cancer treatment. Vitamin D deficiency was defined as 25(OH) D<20 ng/mL. Patients were followed up for a median of 30 months (range: 18-48). Results: The median level of 25(OH)D was 29.0 ng/mL (range: 10...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Jun Yamamura, Shunji Kamigaki, Junya Fujita, Hiroki Osato, Yoshifumi Komoike
BACKGROUND/AIM: Patients with de novo stage IV and recurrent metastatic breast cancer are often treated with the same strategies, although the difference in prognostic outcomes remains unclear. The objective of this retrospective chart review study was to compare the prognostic outcomes between two types of patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. PATIENTS AND METHODS: We estimated overall survival of the two groups and evaluated the progressive course of the disease using disease-free interval (DFI) and interval from the end of adjuvant treatment to the first recurrence (AFI)...
March 2018: In Vivo
Christian Maurer, Arlindo R Ferreira, Samuel Martel, Matteo Lambertini, Noam Pondé, Philippe Aftimos, Evandro de Azambuja, Martine Piccart
This is a single center retrospective analysis of patients with hormone receptor-positive, HER2-negative metastatic breast cancer progressing after ≥ 4 treatment lines treated with palbociclib in combination with endocrine therapy within a compassionate use program. Thirty-four patients were included between 10/2015 and 02/2017, the majority (82.4%) being previously treated with mTOR inhibitors. Disease control rate was 52.9% and 24.4% at week 12 and 24. Overall progression-free survival was 3.1 months with no difference between mTOR inhibitor-pretreated (3...
February 20, 2018: Breast: Official Journal of the European Society of Mastology
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