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Dominika Czaplinska, Monika Górska, Kamil Mieczkowski, Grazyna Peszynska-Sularz, Anna J Zaczek, Hanna M Romanska, Rafal Sadej
INTRODUCTION: Triple-negative breast cancer (TNBC), representing over 15% of all breast cancers, has a poorer prognosis than other subtypes. There is no effective targeted treatment available for the TNBC sufferers. Ribosomal S6 kinases (RSKs) have been previously proposed as drug targets for TNBC based on observations that 85% of these tumors express activated RSKs. MATERIALS AND METHODS: Herein we examined an involvement of RSK1 (p90 ribosomal S6 kinase 1) in a regulation of TNBC growth and metastatic spread in an animal model, which closely imitates human disease...
March 2, 2018: Folia Histochemica et Cytobiologica
R F D van la Parra, A B Tadros, C M Checka, G M Rauch, A Lucci, B D Smith, S Krishnamurthy, V Valero, W T Yang, H M Kuerer
BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified...
February 21, 2018: British Journal of Surgery
In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro
Purpose: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). Materials and Methods: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks...
February 14, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Christoforos Haritos, Kleita Michaelidou, Konstantinos Mavridis, Ioannis Missitzis, Alexandros Ardavanis, John Griniatsos, Andreas Scorilas
Novel molecular markers that address the heterogeneity of breast cancer (BC) and provide meaningful prognostic information for BC patients are needed. Kallikrein-related peptidase 6 (KLK6) is aberrantly expressed and functionally implicated in BC and, like other members of the KLK family, may prove a useful molecular tool for clinical management. Our objective was to assess, for the first time, the clinical relevance of KLK6 mRNA expression in BC. Total RNA was isolated from 165 breast tumors, as well as 100 adjacent non-cancerous tumor specimens...
February 12, 2018: Clinical and Experimental Medicine
Claudia Omarini, Giorgia Guaitoli, Stefania Pipitone, Luca Moscetti, Laura Cortesi, Stefano Cascinu, Federico Piacentini
Triple-negative breast cancer (TNBC) remains the poorest-prognosis breast cancer (BC) subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice...
2018: Cancer Management and Research
Mai F Tolba, Hany A Omar
Immunotherapy comprises a promising new era in cancer therapy. Immune checkpoint inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD-L1 were first approved by the Food and Drug Administration (FDA) for the management of metastatic melanoma in 2011. The approval of this class is being extended to include other types of immunogenic tumors. Although breast cancer (BC) was first categorized as non-immunogenic tumor type, there are certain subsets of BC that showed a high level of tumor infiltrating lymphocytes (TILs)...
January 12, 2018: Critical Reviews in Oncology/hematology
Holly J Pederson, Dharmesh Gopalakrishnan, Ryan Noss, Courtney Yanda, Charis Eng, Stephen R Grobmyer
BACKGROUND: With the advent of multi-gene panel testing for breast cancer patients, germline mutations with unknown association with cancer risk, known as variants of uncertain significance (VUS), are being increasingly identified. Some studies have shown higher rates of contralateral prophylactic mastectomies (CPM) in these patients despite lack of evidence to support this intervention. We analyzed surgical choices in patients who were identified to have VUS. METHODS: A retrospective review was performed of patients with TNBC treated at a single institution after multi-gene panel tests became available (09/01/2013- 02/28/2017)...
January 19, 2018: Journal of the American College of Surgeons
Dhiraj Kumar, Saikat Haldar, Mahadeo Gorain, Santosh Kumar, Fayaj A Mulani, Amit S Yadav, Lucio Miele, Hirekodathakallu V Thulasiram, Gopal C Kundu
BACKGROUND: Breast cancer is one of the most commonly diagnosed invasive cancers among women around the world. Among several subtypes, triple negative breast cancer (TNBC) is highly aggressive and chemoresistant. Treatment of TNBC patients has been challenging due to heterogeneity and devoid of well-defined molecular targets. Thus, identification of novel effective and selective agents against TNBC is essential. METHODS: We used epoxyazadiradione to assess the cell viability, mitochondrial potential, ROS level, cell migration, apoptosis and protein expression in cell culture models of TNBC MDA-MB-231 and ER+ MCF-7 breast cancer cells...
January 8, 2018: BMC Cancer
Heng Sun, Jing Zou, Ling Chen, Xuyu Zu, Gebo Wen, Jing Zhong
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks expression of the estrogen and progesterone receptor and does not overexpress human epidermal growth factor 2 receptor protein. TNBC is associated with special characteristics, including aggressiveness, poor prognosis and poor response to treatment, and has been attracting increasing attention worldwide. Obesity is a well-documented factor exerting a significant effect on the development of breast cancer, including TNBC. The purpose of the present review was to focus on the association between obesity and TNBC and provide a summary of novel research findings...
December 2017: Molecular and Clinical Oncology
Olga Golubnitschaja, Nora Filep, Kristina Yeghiazaryan, Henricus Johannes Blom, Martin Hofmann-Apitius, Walther Kuhn
Breast cancer epidemic in the early twenty-first century results in around two million new cases and half-a-million of the disease-related deaths registered annually worldwide. A particularly dramatic situation is attributed to some specific patient subgroups such as the triple-negative breast cancer (TNBC). TNBC is a particularly aggressive type of breast cancer lacking clear diagnostic approach and targeted therapies. Consequently, more than 50% of the TNBC patients die of the metastatic BC within the first 6 months of the diagnosis...
December 16, 2017: Amino Acids
S M Reddy, C H Barcenas, A K Sinha, L Hsu, S L Moulder, D Tripathy, G N Hortobagyi, V Valero
BACKGROUND: We counsel our triple-negative breast cancer (TNBC) patients that the risk of recurrence is highest in the first 5 years after diagnosis. However, there are limited data with extended follow-up on the frequency, characteristics, and predictors of late events. METHODS: We queried the MD Anderson Breast Cancer Management System database to identify patients with stage I-III TNBC who were disease free at 5 years from diagnosis. The Kaplan-Meier method was used to estimate yearly recurrence-free interval (RFI), recurrence-free survival (RFS), and distant relapse-free survival (DRFS), as defined by the STEEP criteria...
January 2018: British Journal of Cancer
Asmerom Tesfamariam Sengal, Nada Suliman Haj-Mukhtar, Ahmed Mohammed Elhaj, Shahinaz Bedri, Eva Johanna Kantelhardt, Ahmed A Mohamedani
BACKGROUND: Breast cancer is the most common malignancy accounting for 25% of all cancers in females. In Africa, breast cancer prevalence and mortality are steadily increasing. Knowledge of hormone receptors and human epidermal growth factor receptor-2 (HER-2) expressions are vital for breast cancer management plans and decision making. There is wide regional variation in the proportion of these biomarkers, especially in African countries. Hormone receptors positivity in indigenous African and African American women is considered to be low and triple negative breast cancer is a dominant phenotype...
December 1, 2017: BMC Cancer
Michaela Aubele, Manfred Schmitt, Rudolf Napieralski, Stefan Paepke, Johannes Ettl, Magdalena Absmaier, Viktor Magdolen, John Martens, John A Foekens, Olaf G Wilhelm, Marion Kiechle
High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need...
2017: Disease Markers
Zheng Han, Han Cheng, Jenny G Parvani, Zhuxian Zhou, Zheng-Rong Lu
PURPOSE: Non-invasive early accurate detection of malignant breast cancer is paramount to the clinical management of the life-threatening disease. Here, we aim to test a small peptide targeted MRI contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein, extradomain-B fibronectin (EDB-FN), in the tumor microenvironment for MR molecular imaging of breast cancer. METHOD: EDB-FN expression in 4T1 and MDA-MB-231 cancers was analyzed with quantitative real-time PCR and western blot...
October 29, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Ciara C O'Sullivan, Nicole N Davarpanah, Jame Abraham, Susan E Bates
Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287)...
April 2017: Seminars in Oncology
Leisha A Emens
Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) antagonists in small numbers of patients with metastatic breast cancer. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of tumor-infiltrating leukocytes. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple-negative breast cancer (TNBC), suggesting that these agents may transform the lives of responding patients...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hanan Alabdulkareem, Tiffany Pinchinat, Sarah Khan, Alyssa Landers, Paul Christos, Rache Simmons, Tracy-Ann Moo
Breast cancer is the leading cause of cancer death in women younger than 40 years. Triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2 (HER2) positive subtypes have a particularly poor prognosis in this age group. The purpose of this study was to compare rates of recurrence among breast cancer subtypes in young patients treated with modern adjuvant systemic therapy. A retrospective review of breast cancer patients managed at a major academic breast center between May 2000 and November 2014 was performed...
July 14, 2017: Breast Journal
R V Dave, R Millican-Slater, D Dodwell, K Horgan, N Sharma
BACKGROUND: Neoadjuvant chemotherapy (NACT) is increasingly being offered to patients with breast cancer. No survival benefit has been demonstrated for NACT, but it may serve to reduce tumour size and improve prognosis through the attainment of a pathological complete response (pCR). The role and mode of MRI monitoring during NACT remain unclear. METHODS: Patients managed with NACT at a UK centre over 7 years were studied using a prospectively maintained database, which also included details of MRI...
August 2017: British Journal of Surgery
Rachel S Riley, Emily S Day
Antibodies that antagonize cell signaling pathways specific to their targeted receptor are invaluable tools to study and treat malignancies, but their utility is limited by high production costs and treatment dosages. Researchers have shown that antibodies conjugated to nanoparticles display increased affinity for their target relative to freely delivered antibodies due to multivalency, and this study investigates how this multivalency can enable antibody-nanoparticle conjugates to inhibit oncogenic cell signaling more effectively than freely delivered antibodies...
July 2017: Small
Xiao-Hong Li, Xi-Ran He, Yan-Yan Zhou, Hai-Yu Zhao, Wen-Xian Zheng, Shan-Tong Jiang, Qun Zhou, Ping-Ping Li, Shu-Yan Han
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. AIM OF THE STUDY: This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line...
July 12, 2017: Journal of Ethnopharmacology
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