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HER2+ metastatic breast cancer

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
April 11, 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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28364270/safe-trial-an-ongoing-randomized-clinical-study-to-assess-the-role-of-cardiotoxicity-prevention-in-breast-cancer-patients-treated-with-anthracyclines-with-or-without-trastuzumab
#16
REVIEW
Icro Meattini, Giuseppe Curigliano, Francesca Terziani, Carlotta Becherini, Mario Airoldi, Giacomo Allegrini, Domenico Amoroso, Sandro Barni, Carmelo Bengala, Valentina Guarneri, Paolo Marchetti, Francesca Martella, Pierluigi Piovano, Agnese Vannini, Isacco Desideri, Roberto Tarquini, Giorgio Galanti, Giuseppe Barletta, Lorenzo Livi
Over the years, thanks to the addition of new generation systemic agents, as well as the use of more advanced and precise radiotherapy techniques, it was able to obtain a high curability rate for breast cancer. Anthracyclines play a key role in the treatment of breast disease, with a well-known benefit on disease-free survival of patients with positive nodal status. Trastuzumab have shown a significant outcome advantage after 1-year administration in case of HER2-positive disease. Unfortunately, significant increase in cardiotoxicity has been observed after anthracyclines and trastuzumab therapies...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28361859/the-impact-of-locoregional-treatment-on-survival-of-patients-with-primary-metastatic-breast-cancer
#17
R Liubota, V Cheshuk, R Vereshchako, O Zotov, V Zaichuk, N Anikusko, I Liubota
The aim of the study was to investigate the impact of primary tumor locoregional treatment (surgery or/and radiotherapy) on overall survival in patients with primary metastatic breast cancer (PMBC). MATERIALS AND METHODS: This retrospective study included 295 wo-men aged from 23 to 76 years with PMBC. Among the 295 patients, the effect of locoregional treatment of primary tumor on survival outcomes was evaluated in 177 women with distant metastases at diagnosis of breast cancer. 35 patient received breast surgery (group 1), 95 patients with PMBC - radiotherapy (group 2) and 47 patients - combination of breast surgery and radiation (group 3)...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28356770/breast-cancer-in-patients-with-li-fraumeni-syndrome-a-case-series-study-and-review-of-literature
#18
Amara G Nandikolla, Sangeetha Venugopal, Jesus Anampa
BACKGROUND: Li-Fraumeni Syndrome (LFS) is a rare disease with autosomal dominant inheritance linked to germline mutations of tumor suppressor gene TP53. These patients are predisposed to malignancies such as sarcoma, breast cancer, leukemia, and other malignancies. Breast cancer, the most common malignancy in adult patients with LFS, has an early-onset presentation and is usually treated as per the guidelines for the general population due to the limited literature about breast cancer in LFS...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28356261/ribociclib-approved-for-advanced-breast-cancer
#19
(no author information available yet)
The FDA has approved ribociclib combined with aromatase inhibitor therapy for women with metastatic HR-positive, HER2-negative breast cancer. It is the second CDK 4/6 inhibitor approved for these patients, behind palbociclib; a third is under investigation.
March 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28349782/hr-her2-breast-cancers-with-growth-factor-receptor-mediated-emt-have-a-poor-prognosis-and-lapatinib-downregulates-emt-in-mcf-7-cells
#20
Krisha Desai, Radhika Aiyappa, Jyothi S Prabhu, Madhumathy G Nair, Patrick Varun Lawrence, Aruna Korlimarla, Anupama Ce, Annie Alexander, Rohini S Kaluve, Suraj Manjunath, Marjorrie Correa, B S Srinath, Shekhar Patil, Anjali Kalamdani, Msn Prasad, T S Sridhar
Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor-stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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