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https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#1
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#2
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28629464/mir-629-3p-may-serve-as-a-novel-biomarker-and-potential-therapeutic-target-for-lung-metastases-of-triple-negative-breast-cancer
#3
Jin Wang, Cailu Song, Hailin Tang, Chao Zhang, Jun Tang, Xing Li, Bo Chen, Xiaoming Xie
BACKGROUND: Different breast cancer subtypes show distinct tropisms for sites of metastasis. Notably, the lung is the most common site for the first distant recurrence in triple-negative breast cancer (TNBC). The identification of novel biomarkers for lung metastasis is of great importance to improving the outcome of TNBC. In this study, we sought to identify a microRNA (miRNA)-based biomarker and therapeutic target for lung metastasis of TNBC. METHODS: A total of 669 patients without de novo stage IV TNBC were recruited for this study...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28627677/integrated-analysis-of-the-potential-roles-of-mirna%C3%A2-mrna-networks-in-triple-negative-breast-cancer
#4
Huiru Zhu, Meiyu Dai, Xiaoli Chen, Xiang Chen, Shini Qin, Shengming Dai
Triple negative breast cancer (TNBC) is a type of breast cancer where the tumor cells are negative for the estrogen, progesterone and human epidermal growth factor 2 receptors. To date, expression profiling of microRNA (miRNA/miR) and mRNA sequences have been widely applied for the diagnosis of TNBC. In the present study, an integrated analysis of miRNA‑mRNA profiling arrays was performed. A total of five dysregulated miRNAs in patients with TNBC were identified, including upregulated miR‑558 expression and downregulated miR‑320d‑1, miR‑548v, miR‑99a and miR‑21 expression...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627138/predictors-of-brca1-2-genetic-testing-among-black-women-with-breast-cancer-a-population-based-study
#5
Tarsha Jones, Anne Marie McCarthy, Younji Kim, Katrina Armstrong
Evidence shows that Black women diagnosed with breast cancer are substantially less likely to undergo BRCA testing and other multipanel genetic testing compared to White women, despite having a higher incidence of early-age onset breast cancer and triple-negative breast cancer (TNBC). Our study identifies predictors of BRCA testing among Black women treated for breast cancer and examines differences between BRCA testers and nontesters. We conducted an analysis of 945 Black women ages 18-64 diagnosed with localized or regional-stage invasive breast cancer in Pennsylvania and Florida between 2007 and 2009...
June 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28625363/design-synthesis-and-biological-evaluation-of-novel-indolin-2-ones-as-potent-anticancer-compounds
#6
Andong Zhou, Lei Yan, Fangfang Lai, Xiaoguang Chen, Masuo Goto, Kuo-Hsiung Lee, Zhiyan Xiao
The indolin-2-one core is a privileged structure for antitumor agents, especially kinase inhibitors. Twenty-three novel indolin-2-ones were designed by molecular dissection of the anticancer drug indirubin. Seventeen of them exhibited significant inhibition against the tested cell lines, and two of them (1c and 1h) showed IC50 values at the submicromolar level against HCT-116 cells. Compounds 1c and 2c were also potent inhibitors of the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometry was utilized to explore the antitumor mechanism of 1c and 2c with MDA-MB-231 cells, and distinct effects were observed on 2c...
June 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28625320/expression-of-jagged1-notch3-signaling-pathway-and-their-relationship-with-the-tumor-angiogenesis-in-tnbc
#7
Siliang Xue, Lang He, Xiao Zhang, Jin Zhou, Fanghua Li, Xiaoshan Wang
BACKGROUND AND AIMS: Jagged1/Notch3 signaling pathway plays a key role in angiogenesis of breast cancer, but little is known in TNBC. This study was designed to investigate the expression of Jagged1/Notch3 mRNA and protein in TNBC, analyze their correlations with clinicopathological characteristics and prognosis. Moreover, the interrelationship among Jagged1/Notch3 and VEGF was initially evaluated. METHODS: Jagged1/Notch3 mRNA and protein expression levels were determined by Q-RT-PCR and Western blotting...
February 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28624788/systematic-review-and-meta-analysis-of-the-efficacy-of-breast-conservation-therapy-followed-by-radiotherapy-in-four-breast-cancer-subtypes
#8
Xin-Bin Pan, Rou-Jun Chen, Shi-Ting Huang, Yan-Ming Jiang, Xiao-Dong Zhu
The different molecular subtypes of breast cancer are associated with distinct outcomes. We assessed the efficacy of breast conservation therapy (BCT) followed by radiotherapy for patients with different breast cancer subtypes. We searched the MEDLINE, EMBASE, and Cochrane Library databases to identify studies published prior to April 30, 2016 that assessed the efficacy of BCT followed by radiotherapy in breast cancer patients with different molecular subtypes. A meta-analysis of seven studies that included 3,798 luminal A, 770 luminal B, 344 human epidermal growth factor receptor 2 (Her-2), and 767 triple-negative breast cancer (TNBC) patients was performed...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624192/stimuli-responsive-mesoporous-silica-nps-as-non-viral-dual-sirna-chemotherapy-carriers-for-triple-negative-breast-cancer
#9
REVIEW
Behrad Darvishi, Leila Farahmand, Keivan Majidzadeh-A
Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. It is associated with a very poor prognosis and intrinsically resistant to several conventional and targeted chemotherapy agents and has a 5-year survival rate of less than 25%. Because the treatment options for TNBC are very limited and not efficient enough for achieving minimum desired goals, shifting toward a new generation of anti-cancer agents appears to be very critical. Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623645/psmb5-is-associated-with-proliferation-and-drug-resistance-in-triple-negative-breast-cancer
#10
Wensong Wei, Yufeng Zou, Qihua Jiang, Zhibin Zhou, Haolong Ding, Liping Yan, Shixin Yang
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development...
June 15, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28619708/arhgap18-downregulation-by-mir-200b-suppresses-metastasis-of-triple-negative-breast-cancer-by-enhancing-activation-of-rhoa
#11
Brock Humphries, Zhishan Wang, Yunfei Li, Jing-Ru Jhan, Yiguo Jiang, Chengfeng Yang
Rho GTPases activated in cancer cells drive proliferation, migration and metastasis. Thus, RhoGAP proteins which negatively regulate Rho GTPases are generally thought to function as tumor suppressors. Here this expectation was challenged by characterization of ARHGAP18, a RhoGAP family member that is selectively overexpressed in highly migratory triple negative breast cancer (TNBC) cells. In human breast tumors, higher ARHGAP18 levels associated with worse overall survival, recurrence-free survival and metastasis-free survival...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28618929/anti-tumorigenic-effects-of-a-novel-digitoxin-derivative-on-both-estrogen-receptor-positive-and-triple-negative-breast-cancer-cells
#12
Yogesh M Kulkarni, Juan S Yakisich, Neelam Azad, Rajkumar Venkatadri, Vivek Kaushik, George O'Doherty, Anand Krishnan V Iyer
While there are targeted treatments for triple positive breast cancers, lack of specific biomarkers for triple-negative breast cancers (TNBC) has hindered the development of therapies for this subset of cancers. In this study, we evaluated the anticancer properties of cardiac glycoside Digitoxin (Dtx) and its synthetic analog MonoD on breast cancer cell lines MCF-7 (estrogen receptor-positive breast cancer) and MDA-MB-468 (triple-negative breast cancer). Both cardiac glycosides, at concentrations within the therapeutic range, increased the fraction of cells in the G0/G1 phase of the cell cycle, decreased viability, and inhibited the migration of MCF-7 and MDA-MB-468 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28616768/antitumor-activity-and-safety-profile-of-weekly-carboplatin-plus-paclitaxel-in-metastatic-breast-cancer-a-ten-year-monocentric-retrospective-study
#13
Claudio Vernieri, Monica Milano, Alessia Mennitto, Claudia Maggi, Benvenuto Ferrari, Lucia Rinaldi, Roberta Mennitto, Claudia Stefanetti, Barbara Re, Gabriella Mariani, Giulia Bianchi, Giuseppe Capri, Filippo de Braud
BACKGROUND: Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum-taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS). METHODS: We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007-2016 with the combination of carboplatin AUC 2 plus paclitaxel 80 mg/m(2), both given on days 1 and 8 in every 21-day cycle...
June 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28615672/reconstruction-of-pathway-modification-induced-by-nicotinamide-using-multi-omic-network-analyses-in-triple-negative-breast-cancer
#14
Ji Young Kim, Hyebin Lee, Jongmin Woo, Wang Yue, Kwangsoo Kim, Seongmin Choi, Ja-June Jang, Youngsoo Kim, In Ae Park, Dohyun Han, Han Suk Ryu
Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615523/phytoagent-deoxyelephantopin-derivative-inhibits-triple-negative-breast-cancer-cell-activity-by-inducing-oxidative-stress-mediated-paraptosis-like-cell-death
#15
Jeng-Yuan Shiau, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
Triple negative breast cancer (TNBC) is a highly metastatic cancer among the breast cancer subgroups. A thorny issue for clinical therapy of TNBC is lack of an efficient targeted therapeutic strategy. We previously created a novel sesquiterpene lactone analog (named DETD-35) derived from plant deoxyelephantopin (DET) which exhibits potent effects against human TNBC MDA-MB-231 tumor growth in a xenograft mouse model. Here we studied the mechanisms of both DET and DETD-35 against MDA-MB-231 cells. DETD-35 (3-fold decreased in IC50) exhibited better anti-TNBC cell activity than DET as observed through induction of reactive oxygen species production (within 2 h treatment) and damage to the ER structures, resulting in ER-derived cytoplasmic vacuolation and ubiquitinated protein accumulation in the treated cells...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612435/racial-disparities-in-survival-outcomes-by-breast-tumor-subtype-among-african-american-women-in-memphis-tennessee
#16
Gregory Vidal, Zoran Bursac, Gustavo Miranda-Carboni, Shelley White-Means, Athena Starlard-Davenport
Racial disparities in survival among African American (AA) women in the United States have been well documented. Breast cancer mortality rates among AA women is higher in Memphis, Tennessee as compared to 49 of the largest US cities. In this study, we investigated the extent to which racial/ethnic disparities in survival outcomes among Memphis women are attributed to differences in breast tumor subtype and treatment outcomes. A total of 3527 patients diagnosed with stage I-IV breast cancer between January 2002 and April 2015 at Methodist Health hospitals and West Cancer Center in Memphis, TN were included in the analysis...
June 14, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28611537/therapeutic-advances-and-new-directions-for-triple-negative-breast-cancer
#17
REVIEW
Eleni Andreopoulou, Catherine M Kelly, Hayley M McDaid
Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely BRCA1 and 2, and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP)...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28611536/germline-mutations-in-triple-negative-breast-cancer
#18
REVIEW
Eric Hahnen, Jan Hauke, Christoph Engel, Guido Neidhardt, Kerstin Rhiem, Rita K Schmutzler
Triple-negative breast cancer (TNBC) is associated with a poor prognosis and defines a subgroup of patients who do not benefit from endocrine or anti-HER2 therapy. Rather than being a biological entity, TNBC represents a heterogeneous disease, and further subtyping is necessary to establish targeted therapies. Germline mutational status may serve as a robust biomarker predicting therapy response, especially with respect to compounds challenging the DNA repair machinery. Patients with TNBC usually show an early onset of the disease, as well as a positive family history of breast and/or ovarian cancer in more than one third of all cases, which suggests that TNBC is closely associated with a hereditary disease cause...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28611535/biological-subtypes-of-triple-negative-breast-cancer
#19
REVIEW
Michael Hubalek, Theresa Czech, Hannes Müller
Triple-negative breast cancers (TNBCs) are defined as tumors that are negative for estrogen, progesterone and HER-2 receptor. At a percentage of 10-20% TNBCs represent a minority in all breast cancers. However, because of the poor prognosis this particular subtype, triple negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. Identification of its subtypes is essential for understanding the biological characteristics and clinical behavior of TNBC, as well as for developing personalized treatments...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28611280/efficacy-of-adjuvant-chemotherapy-with-carboplatin-for-early-triple-negative-breast-cancer-a-single-center-experience
#20
Marcus Vetter, Spyridon Fokas, Ewelina Biskup, Thomas Schmid, Fabienne Schwab, Andreas Schoetzau, Uwe Güth, Christoph Rochlitz, Rosanna Zanetti-Dällenbach
BACKGROUND: Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. METHODS: We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients...
May 23, 2017: Oncotarget
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