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Metastatic her2+ breast cancer

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https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#1
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445153/increased-risk-of-brain-metastases-in-women-with-breast-cancer-and-p16-expression-in-metastatic-lymph-nodes
#2
Elise Furet, Morad El Bouchtaoui, Jean-Paul Feugeas, Catherine Miquel, Christophe Leboeuf, Clémentine Beytout, Philippe Bertheau, Emilie Le Rhun, Jacques Bonneterre, Anne Janin, Guilhem Bousquet
PURPOSE: Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. RESULTS: Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443700/role-of-everolimus-in-the-treatment-of-metastatic-her2-negative-hr-positive-breast-cancer
#3
Pronzato Paolo
Metastatic breast cancer (mBC) is a leading cause of mortality for women around the world. The response to hormonotherapy of the patients with HER2-negative/HR-positive mBC is usually limited, and many strategies are in place to contrast the hormonotherapy resistance. Since efficacy and effectiveness of everolimus have been established by many trials, this review is aimed to give a structured synthesis to define the everolimus clinical role among the treatment options for mBC. Key aspects of everolimus dosing and safety profile, drawn up by relevant findings, are included, as well as the role of biomarkers to identify subgroups of mBC patients who may best benefit from everolimus treatment...
April 26, 2017: Future Oncology
https://www.readbyqxmd.com/read/28442763/impact-of-hormone-receptor-status-and-distant-recurrence-free-interval-on-survival-benefits-from-trastuzumab-in-her2-positive-metastatic-breast-cancer
#4
Hai-Yuan Yang, Ding Ma, Yi-Rong Liu, Xin Hu, Jian Zhang, Zhong-Hua Wang, Gen-Hong Di, Xi-Chun Hu, Zhi-Ming Shao
We sought to investigate the impact of hormone receptor (HR) status and distant recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit from palliative trastuzumab-containing treatment in HER2-positive metastatic breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2-positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC patients (median: 30.7 months, IQR: 18.5-45.9, P < 0.001) was significant longer compared with HR-HER2+ patients. Patients were categorized into four subgroups based on HR status and palliative trastuzumab (trast+) received...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28438884/safety-evaluation-of-trastuzumab-emtansine-in-japanese-patients-with-her2-positive-advanced-breast-cancer
#5
Junichiro Watanabe, Yoshinori Ito, Toshiaki Saeki, Norikazu Masuda, Toshimi Takano, Shintaro Takao, Kazuhiko Nakagami, Koichiro Tsugawa, Shintaro Nakagawa, Kazumitsu Kanatani, Takahiro Nakayama
BACKGROUND/AIM: Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab. PATIENTS AND METHODS: Patients with inoperable or recurrent breast cancer who were previously treated with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were included. T-DM1 3.6 mg/kg was administered intravenously every 21 days...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28430631/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#6
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428285/characterisation-of-gata3-expression-in-invasive-breast-cancer-differences-in-histological-subtypes-and-immunohistochemically-defined-molecular-subtypes
#7
Tang Shaoxian, Yu Baohua, Xu Xiaoli, Cheng Yufan, Tu Xiaoyu, Lu Hongfen, Bi Rui, Sun Xiangjie, Shui Ruohong, Yang Wentao
AIMS: GATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases...
April 20, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28427196/breast-cancer-subtypes-predict-the-preferential-site-of-distant-metastases-a-seer-based-study
#8
Qi Wu, Juanjuan Li, Shan Zhu, Juan Wu, Chuang Chen, Qian Liu, Wen Wei, Yimin Zhang, Shengrong Sun
BACKGROUND AND AIMS: This study aimed to access possible relationships between breast cancer subtypes and sites of distant metastasis in breast cancer. RESULTS: A total of 243,896 patients, including 226,451 cases in control groups were identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases. Patients with all subtypes were most prone to bone metastases, the incidence of bone metastasis in HR+/HER2+ subtype was up to 5...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422142/g-protein-coupled-kiss1-receptor-is-overexpressed-in-triple-negative-breast-cancer-and-promotes-drug-resistance
#9
Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya
Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418889/efficacy-and-safety-of-everolimus-in-chinese-metastatic-hr-positive-her2-negative-breast-cancer-patients-a-real-world-retrospective-study
#10
Chengcheng Gong, Yannan Zhao, Biyun Wang, Xichun Hu, Zhonghua Wang, Jian Zhang, Sheng Zhang
BACKGROUND: Everolimus combined with endocrine therapy has been proved to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). We aimed to evaluate the efficacy and safety of everolimus plus endocrine therapy in Chinese real-world practice for the first time, and investigate factors associated with efficacy. METHODS: Seventy-five HR+/HER2- MBC patients were included in this retrospective study who received everolimus plus endocrine therapy after progression on prior endocrine therapy in Fudan University Shanghai Cancer Center (FUSCC) between June 2013 and February 2016...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417332/assessment-of-the-prognostic-and-discriminating-value-of-the-novel-bioscore-system-for-breast-cancer-a-seer-database-analysis
#11
Omar Abdel-Rahman
BACKGROUND: An updated bioscore has been proposed within the context of the 8th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer. This study seeks to validate the discriminating value of this bioscore among non-metastatic breast cancer patients registered within the surveillance, epidemiology, and end results (SEER) database. METHODS: Through SEER*Stat program, SEER database (2010-2013) was accessed and bioscore was formulated for each patient...
April 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28416639/absent-progesterone-receptor-expression-in-the-lymph-node-metastases-of-er-positive-her2-negative-breast-cancer-is-associated-with-relapse-on-tamoxifen
#12
Cameron E Snell, Madeline Gough, Kathryn Middleton, Michael Hsieh, Lauren Furnas, Brenton Seidl, Kristen Gibbons, Christopher Pyke, Catherine Shannon, Natasha Woodward, Jane E Armes
AIMS: Progesterone receptor (PR) expression is prognostic in early stage breast cancer. There are several reports of discordant expression between primary tumour and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER) and PR. We sought to determine whether expression of these biomarkers in the synchronous ALN metastases of ER positive (+), HER2 negative (-) breast cancer could provide more accurate prognostic information. METHODS: The retrospective cohort included 229 patients from a single institution with ER+, HER2- breast cancer who had synchronous ALN metastatic disease (2005-2014)...
April 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28415615/a-nation-wide-multicenter-10-year-1999-2008-retrospective-study-of-chemotherapy-in-chinese-breast-cancer-patients
#13
Qiao Li, Zhao Yang, Jinhu Fan, Jianjun He, Bin Zhang, Hongjian Yang, Xiaoming Xie, Zhonghua Tang, Hui Li, Youlin Qiao, Pin Zhang
Little information is available on the evolvement of chemotherapeutic regimens administered to Chinese females with breast cancer. We retrospectively analyzed demographic, pathological and chemotherapeutic data of 4211 breast cancer patients, who were randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. A total of 3271 cases (77.7%) received adjuvant chemotherapy, 558 (13.3%) received neoadjuvant chemotherapy, and 392 (9.3%) received chemotherapy for metastatic disease...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415567/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#14
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413662/phase-i-study-of-nanoparticle-albumin-bound-paclitaxel-carboplatin-and-trastuzumab-in-women-with-human-epidermal-growth-factor-receptor-2-overexpressing-breast-cancer
#15
Kenji Tezuka, Tsutomu Takashima, Shinichiro Kashiwagi, Hidemi Kawajiri, Shinya Tokunaga, Seika Tei, Shigehiko Nishimura, Shigehito Yamagata, Satoru Noda, Takeo Nishimori, Yoko Mizuyama, Takeshi Sunami, Katsumi Ikeda, Yoshinari Ogawa, Naoyoshi Onoda, Tetsuro Ishikawa, Shinzoh Kudoh, Minoru Takada, Kosei Hirakawa
Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28406988/peptide-probes-derived-from-pertuzumab-by-molecular-dynamics-modeling-for-her2-positive-tumor-imaging
#16
Xiaoliang Yang, Zihua Wang, Zhichu Xiang, Dan Li, Zhiyuan Hu, Wei Cui, Lingling Geng, Qiaojun Fang
A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a β hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28395543/pharmacokinetic-drug-evaluation-of-ribociclib-for-the-treatment-of-metastatic-hormone-positive-breast-cancer
#17
Giuseppe Curigliano, Carmen Criscitiello, Angela Esposito, Mattia Intra, Saverio Minucci
Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer. Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer...
May 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28388007/aberrant-intracellular-metabolism-of-t-dm1-confers-t-dm1-resistance-in-her2-positive-gastric-cancer-cells
#18
Hongbin Wang, Wenqian Wang, Yongping Xu, Yong Yang, Xiaoyan Chen, Haitian Quan, Liguang Lou
T-DM1 (Kadcyla), an antibody-drug conjugate (ADC) consisting of HER2-targeted monoclonal antibody trastuzumab linked to anti-microtubule agent mertansine (DM1), has been approved for the treatment of HER2-positive metastatic breast cancer. To date, acquired resistance arises to be a major obstacle to T-DM1 treatment, and mechanisms remain incompletely understood. In the present study, we established a T-DM1-resistant N87-KR cell line from HER2-positive N87 gastric cancer cells to investigate mechanisms of acquired resistance and develop strategies for overcoming it...
April 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28385537/phase-i-trial-of-everolimus-and-capecitabine-in-metastatic-her2-breast-cancer
#19
Gregory A Vidal, Mary Chen, Shruti Sheth, Tiffany Svahn, Ellie Guardino
BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is a driver of breast tumorigenesis. The mTOR inhibitor everolimus reverses antihormonal therapy resistance and is an approved therapy for metastatic breast cancer. A synergistic effect with fluoropyrimidine has been suggested. The present study evaluated the safety and tolerability of an all-oral combination of everolimus and capecitabine for metastatic breast cancer (MBC). PATIENTS AND METHODS: MBC patients naive to capecitabine and mTOR inhibitors who had received ≤ 3 previous chemotherapy regimens in the metastatic setting were eligible for the present study...
March 16, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28373443/dynamic-phenotypic-transition-of-breast-cancer-cells-in-vitro-revealed-by-self-floating-cell-culture
#20
Yusuke Oku, Naoyuki Nishiya, Kayoko Tsuda, Masahiko Shibazaki, Chihaya Maesawa, Yoshimasa Uehara
BACKGROUND: Breast tumor heterogeneity leads to phenotypic diversity, such as tumor-initiating and metastatic properties and drug sensitivity. MATERIALS AND METHODS: We found that a self-floating cell (SFC) culture enriches a drug-resistant subpopulation in a HER2-positive breast cancer cell line. SFCs were analyzed for cancer stem cell markers, gene expression profiles, and sensitivity for anticancer drugs. RESULTS: SFCs expressed cancer stem cell markers, such as aldehyde dehydrogenase (ALDH) activity and elevated HER2 autophosphorylation...
April 2017: Anticancer Research
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