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HER2+ metastatic breast cancer

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https://www.readbyqxmd.com/read/28324269/metformin-sensitizes-triple-negative-breast-cancer-to-proapoptotic-trail-receptor-agonists-by-suppressing-xiap-expression
#1
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
PURPOSE: Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. METHODS: Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28324265/cardiac-safety-efficacy-and-correlation-of-serial-serum-her2-extracellular-domain-shed-antigen-measurement-with-the-outcome-of-the-combined-trastuzumab-plus-cmf-in-women-with-her2-positive-metastatic-breast-cancer-results-from-the-eortc-10995-phase-ii-study
#2
Konstantinos Tryfonidis, S Marreaud, H Khaled, B De Valk, J Vermorken, M Welnicka-Jaskiewicz, K Aalders, J M S Bartlett, L Biganzoli, J Bogaerts, David Cameron
PURPOSE: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC). METHODS: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.0) were enrolled. Initially, patients were randomized between 8 CMF cycles alone or combined with trastuzumab during chemotherapy, followed by 3-weekly trastuzumab maintenance till progression...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28316212/-evaluation-and-classification-of-drug-therapy-for-breast-cancer-with-bone-only-metastasis
#3
X Y Meng, S T Song
Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28315066/failure-patterns-according-to-molecular-subtype-in-patients-with-invasive-breast-cancer-following-postoperative-adjuvant-radiotherapy-long-term-outcomes-in-contemporary-clinical-practice
#4
Yu Jin Lim, Sea-Won Lee, Noorie Choi, Jeanny Kwon, Keun-Yong Eom, Eunyoung Kang, Eun-Kyu Kim, Sung-Won Kim, Jee Hyun Kim, Yu Jung Kim, Se Hyun Kim, So Yeon Park, Jae-Sung Kim, In Ah Kim
PURPOSE: Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. METHODS: We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St...
March 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28314836/safe-heart-rationale-and-design-of-a-pilot-study-investigating-cardiac-safety-of-her2-targeted-therapy-in-patients-with-her2-positive-breast-cancer-and-reduced-left-ventricular-function
#5
Filipa Lynce, Ana Barac, Ming T Tan, Federico M Asch, Karen L Smith, Chau Dang, Claudine Isaacs, Sandra M Swain
BACKGROUND: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function. METHODS: The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314691/prevention-of-everolimus-related-stomatitis-in-women-with-hormone-receptor-positive-her2-negative-metastatic-breast-cancer-using-dexamethasone-mouthwash-swish-a-single-arm-phase-2-trial
#6
Hope S Rugo, Lasika Seneviratne, J Thaddeus Beck, John A Glaspy, Julio A Peguero, Timothy J Pluard, Navneet Dhillon, Leon Christopher Hwang, Chaitali Nangia, Ingrid A Mayer, Timothy F Meiller, Mark S Chambers, Robert W Sweetman, J Randy Sabo, Jennifer K Litton
BACKGROUND: Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. METHODS: This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer...
March 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28314310/first-line-bevacizumab-and-paclitaxel-for-her2-negative-metastatic-breast-cancer-a-french-retrospective-observational-study
#7
Veronique Dieras, Simona Pop, Frederique Berger, Marie-Eglantine Dujaric, Philippe Beuzeboc, Laurence Escalup, François Clement Bidard, Paul Henri Cottu, Christophe LE Tourneau, Sophie Piperno-Neumann, Valerie Laurence, Mathieu Robain, Bernard Asselain, Jean-Yves Pierga
AIM: To assess outcomes in patients treated with first-line bevacizumab-containing therapy for human epidermal growth factor receptor (HER)2-negative metastatic breast cancer (mBC) at a single centre with a homogenous standard-of-care. PATIENTS AND METHODS: Information on patient and disease characteristics, efficacy, and safety was extracted from computer-based records of all patients receiving first-line bevacizumab-paclitaxel at the Curie Institute, Paris, France, between 2008 and 2011...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314283/stable-shrna-silencing-of-lactate-dehydrogenase-a-ldha-in-human-mda-mb-231-breast-cancer-cells-fails-to-alter-lactic-acid-production-glycolytic-activity-atp-or-survival
#8
Nzinga Mack, Elizabeth A Mazzio, David Bauer, Hernan Flores-Rozas, Karam F A Soliman
BACKGROUND: In the US, African Americans have a high death rate from triple-negative breast cancer (TNBC), characterized by lack of hormone receptors (ER, PR, HER2/ERRB2) which are otherwise valuable targets of chemotherapy. There is a need to identify novel targets that negatively impact TNBC tumorigenesis. TNBCs release an abundance of lactic acid, under normoxic, hypoxic and hyperoxic conditions; this referred to as the Warburg effect. Accumulated lactic acid sustains peri-cellular acidity which propels metastatic invasion and malignant aggressive transformation...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28301662/brain-metastases-in-newly-diagnosed-breast-cancer-a-population-based-study
#9
Allison M Martin, Daniel N Cagney, Paul J Catalano, Laura E Warren, Jennifer R Bellon, Rinaa S Punglia, Elizabeth B Claus, Eudocia Q Lee, Patrick Y Wen, Daphne A Haas-Kogan, Brian M Alexander, Nancy U Lin, Ayal A Aizer
Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Design, Setting, and Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute...
March 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28298546/64cu-mm-302-positron-emission-tomography-quantifies-variability-of-enhanced-permeability-and-retention-of-nanoparticles-in-relation-to-treatment-response-in-patients-with-metastatic-breast-cancer
#10
Helen Lee, Anthony F Shields, Barry A Siegel, Kathy D Miller, Ian Krop, Cynthia X Ma, Patricia M LoRusso, Pamela N Munster, Karen Campbell, Daniel F Gaddy, Shannon C Leonard, Elena Geretti, Stephanie J Blocker, Dmitri B Kirpotin, Victor Moyo, Thomas J Wickham, Bart S Hendriks
PURPOSE: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies. EXPERIMENTAL DESIGN: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by Positron Emission Tomography/Computed Tomography (PET/CT)...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28288388/increased-life-expectancy-as-a-result-of-non-hormonal-targeted-therapies-for-her2-or-hormone-receptor-positive-metastatic-breast-cancer-a-systematic-review-and-meta-analysis
#11
REVIEW
Rositsa G Koleva-Kolarova, Monika P Oktora, Annelies L Robijn, Marcel J W Greuter, Anna K L Reyners, Erik Buskens, Geertruida H de Bock
This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI)...
February 20, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28259011/clinical-use-of-biomarkers-in-breast-cancer-updated-guidelines-from-the-european-group-on-tumor-markers-egtm
#12
REVIEW
M J Duffy, N Harbeck, M Nap, R Molina, A Nicolini, E Senkus, F Cardoso
Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour...
February 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28256066/a-randomized-phase-ii-study-of-nab-paclitaxel-as-first-line-chemotherapy-in-patients-with-her2-negative-metastatic-breast-cancer
#13
Kenji Tamura, Kenichi Inoue, Norikazu Masuda, Shintaro Takao, Masahiro Kashiwaba, Yutaka Tokuda, Hiroji Iwata, Naohito Yamamoto, Kenjiro Aogi, Toshiaki Saeki, Takahiro Nakayama, Nobuaki Sato, Tatsuya Toyama, Takanori Ishida, Hitoshi Arioka, Mitsue Saito, Shinji Ohno, Hideko Yamauchi, Kimito Yamada, Junichiro Watanabe, Hiroshi Ishiguro, Yasuhiro Fujiwara
Weekly administration of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has been shown to be a safe and effective treatment for metastatic breast cancer (MBC) in clinical studies. We conducted a multicenter, randomized, open-label phase II study to compare the efficacy and safety of weekly nab-paclitaxel and docetaxel in Japanese patients with human epidermal growth factor receptor 2-negative MBC. The primary endpoint was progression-free survival (PFS). Patients were randomized to receive nab-paclitaxel (150 mg/m(2) nab-paclitaxel once per week for 3 of 4 weeks; n = 100) or docetaxel (75 mg/m(2) docetaxel every 3 weeks; n = 100)...
March 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28253566/bilateral-salpingo-oophorectomy-compared-to-gonadotropin-releasing-hormone-agonists-in-premenopausal-hormone-receptor-positive-metastatic-breast-cancer-patients-treated-with-aromatase-inhibitors
#14
Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim
Purpose: Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO). Materials and Methods: We retrospectively analyzed data of 66 premenopausal patients with HR-positive, HER2-negative recurrent and metastatic breast cancer (MBC) who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015...
February 27, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28249905/intrinsic-subtypes-and-gene-expression-profiles-in-primary-and-metastatic-breast-cancer
#15
Juan Miguel Cejalvo, Eduardo Martínez de Dueñas, Patricia Galvan, Susana García-Recio, Octavio Burgués Gasión, Laia Paré, Silvia Antolin, Rossella Martinello, Isabel Blancas, Barbara Adamo, Angel Guerrero-Zotano, Montserrat Muñoz, Paolo Nuciforo, María Vidal, Ramón M Pérez, José Ignacio Chacón López-Muñiz, Rosalía Caballero, Vicente Peg, Eva Carrasco, Federico Rojo, Charles M Perou, Javier Cortes, Vincenzo Adamo, Joan Albanell, Roger R Gomis, Ana Lluch, Aleix Prat
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and Chi-square tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors and 55...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28247034/genomic-characteristics-of-trastuzumab-resistant-her2-positive-metastatic-breast-cancer
#16
Mateus de Oliveira Taveira, Sheida Nabavi, Yuker Wang, Peter Tonellato, Francisco J Esteva, Lewis C Cantley, Gerburg M Wulf
PURPOSE: Resistance to trastuzumab therapy is linked to phosphoinositol 3-kinase (PI3K) pathway activation. One key downstream effector and regulator of this pathway is the mechanistic target of rapamycin (mTOR). In 2011, a phase I/II study evaluated the combination of trastuzumab and everolimus (a mTOR inhibitor) for treatment of Her2-positive metastatic breast cancer (MBC) for patients who had progressed on trastuzumab-based therapy. METHODS: We retrospectively analyzed GeneChip microarray data from 22 of 47 patients included in the study...
February 28, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28245951/real-world-and-trial-based-cost-effectiveness-analysis-of-bevacizumab-in-her2-negative-metastatic-breast-cancer-patients-a-study-of-the-southeast-netherlands-breast-cancer-consortium
#17
R J W van Kampen, B L T Ramaekers, D J A Lobbezoo, M de Boer, M W Dercksen, F van den Berkmortel, T J Smilde, A J van de Wouw, F P J Peters, J M G van Riel, N A J B Peters, V C G Tjan-Heijnen, M A Joore
INTRODUCTION: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial. METHODS: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively...
February 25, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28243895/effects-of-hormone-receptor-status-on-the-durable-response-of-trastuzumab-based-therapy-in-metastatic-breast-cancer
#18
Hyung Soon Park, Joohyuk Sohn, Seung Il Kim, Seho Park, Hyung Seok Park, Seul Ghi Gho, Hyun Cheol Chung, Soonmyung Paik, Gun Min Kim
PURPOSE: Trastuzumab-based treatment is the standard care for patients with HER2+ metastatic breast cancer (MBC). About 10% of HER2+ MBC showed a long-term durable response (progression-free survival, PFS > 3 years) to trastuzumab-based therapy. The aim of this study is to identify clinico-pathologic factors for a durable response to trastuzumab-based therapy in HER2-positive MBC. METHODS: In the Yonsei Breast Cancer MBC Database, we identified 1218 MBC patients who were diagnosed from 2006 to 2015...
February 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28241804/expression-of-enhancer-of-zeste-homolog-2-correlates-with-survival-outcome-in-patients-with-metastatic-breast-cancer-exploratory-study-using-primary-and-paired-metastatic-lesions
#19
Hitoshi Inari, Nobuyasu Suganuma, Kae Kawachi, Tatsuya Yoshida, Takashi Yamanaka, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Hirotaka Nakayama, Ayumi Yamanaka, Katsuhiko Masudo, Takashi Oshima, Tomoyuki Yokose, Yasushi Rino, Satoru Shimizu, Yohei Miyagi, Munetaka Masuda
BACKGROUND: In metastatic breast cancer, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as the Ki-67 index sometimes change between primary and metastatic lesions. However, the change in expression levels of enhancer of zeste homolog 2 (EZH2) between primary and metastatic lesions has not been determined in metastatic breast cancer. METHODS: Ninety-six metastatic breast cancer patients had biopsies or resections of metastatic lesions between September 1990 and February 2014 at the Kanagawa Cancer Center...
February 27, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28241044/medico-economic-impact-of-mskcc-non-sentinel-node-prediction-nomogram-for-er-positive-her2-negative-breast-cancers
#20
Hélène Bonsang-Kitzis, Delphine Mouttet-Boizat, Eugénie Guillot, Jean-Guillaume Feron, Virginie Fourchotte, Séverine Alran, Jean-Yves Pierga, Paul Cottu, Florence Lerebours, Denise Stevens, Anne Vincent-Salomon, Brigitte Sigal-Zafrani, François Campana, Roman Rouzier, Fabien Reyal
BACKGROUND: Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. PURPOSE: The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. METHODS: We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB...
2017: PloS One
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