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https://www.readbyqxmd.com/read/29456471/neoadjuvant-chemotherapy-exerts-selection-pressure-towards-luminal-phenotype-breast-cancer
#1
Giulia Galli, Giacomo Bregni, Stefano Cavalieri, Luca Porcu, Paolo Baili, Amash Hade, Francesca Di Salvo, Milena Sant, Roberto Agresti, Massimiliano Gennaro, Secondo Folli, Maria C De Santis, Biagio Paolini, Maria L Carcangiu, Filippo de Braud, Serena Di Cosimo
Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29455872/-pd-l1-expression-and-pd-1-pd-l1-inhibitors-in-breast-cancer
#2
REVIEW
Audrey Monneur, Anthony Gonçalves, François Bertucci
The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing)...
February 15, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29453409/a-potential-prognostic-long-noncoding-rna-signature-to-predict-recurrence-among-er-positive-breast-cancer-patients-treated-with-tamoxifen
#3
Kang Wang, Jie Li, Yong-Fu Xiong, Zhen Zeng, Xiang Zhang, Hong-Yuan Li
Limited predictable long noncoding RNA (lncRNA) signature was reported in tamoxifen resistance among estrogen receptor (ER)-positive breast cancer (BC) patients. The aim of this study was to identify and assess prognostic lncRNA signature to predict recurrence among ER-positive BC patients treated with tamoxifen. Cohorts from Gene Expression Omnibus (GEO) (n = 298) and The Cancer Genome Atlas (TCGA) (n = 160) were defined as training and validation cohort, respectively. BC relapse associated lnRNAs was identify within training cohort, and the predictable value of recurrence was assessed in both cohorts...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#4
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29451783/sufex-click-chemistry-enabled-late-stage-drug-functionalization
#5
Zilei Liu, Jie Li, Suhua Li, Gencheng Li, K Barry Sharpless, Peng Wu
Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the S VI -F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products...
February 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29450494/comparison-of-the-performance-of-6-prognostic-signatures-for-estrogen-receptor-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#6
Ivana Sestak, Richard Buus, Jack Cuzick, Peter Dubsky, Ralf Kronenwett, Carsten Denkert, Sean Ferree, Dennis Sgroi, Catherine Schnabel, Frederick L Baehner, Elizabeth Mallon, Mitch Dowsett
Importance: Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. Objective: To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years. Design, Setting, and Participants: This retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)-negative breast cancer...
February 15, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29448311/enhancing-decision-making-about-adjuvant-chemotherapy-in-early-breast-cancer-following-endopredict-testing
#7
Lesley Fallowfield, Lucy Matthews, Shirley May, Valerie Jenkins, David Bloomfield
Chemotherapy side-effects can be substantial. There is increasing recognition that some oestrogen receptor positive (ER+ve), human epidermal growth factor receptor 2 negative (HER2-ve) patients with breast cancer derive no benefit from chemotherapy and experience only iatrogenic harm. Gene expression profiling tests help refine recurrence risk and likely chemotherapy benefit. EndoPredict® is one such test, which classifies risks of distant recurrence as low or high in patients treated with surgery and adjuvant endocrine therapy alone...
February 15, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29445928/efficacy-and-safety-of-trastuzumab-lapatinib-and-paclitaxel-neoadjuvant-treatment-with-or-without-prolonged-exposure-to-anti-her2-therapy-and-with-or-without-hormone-therapy-for-her2-positive-primary-breast-cancer-a-randomised-five-arm-multicentre-open-label
#8
N Masuda, M Toi, N Yamamoto, H Iwata, K Kuroi, H Bando, S Ohtani, T Takano, K Inoue, Y Yanagita, H Kasai, S Morita, T Sakurai, S Ohno
BACKGROUND: Dual blockade of HER2 promises increased pathological complete response (pCR) rate compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. Many questions remain regarding optimal duration of treatment and combination impact of endocrine therapy for luminal HER2 disease. METHODS: We designed a randomised phase II, five-arm study to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs...
February 14, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29445914/interaction-between-dietary-acrylamide-intake-and-genetic-variants-for-estrogen-receptor-positive-breast-cancer-risk
#9
Janneke G F Hogervorst, Piet A van den Brandt, Roger W L Godschalk, Frederik-Jan van Schooten, Leo J Schouten
PURPOSE: The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology. METHODS: The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach...
February 14, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29445233/in-vitro-cytotoxicity-activity-of-novel-schiff-base-ligand-lanthanide-complexes
#10
Kavitha Andiappan, Anandhavelu Sanmugam, Easwaramoorthy Deivanayagam, K Karuppasamy, Hyun-Seok Kim, Dhanasekaran Vikraman
A Schiff base ligand (SBL), N 2 , N 3 -bis (anthracen-9-ylmethylene) pyridine-2, 3-diamine, was synthesized through the condensation of 2,6-diaminopyridine and anthracene-9-carbaldehyde using a 1:2 ratio. 1 H NMR spectra confirmed the observation of non-involvement aromatic carboxylic proton in SBL. A novel series of lanthanide (i.e., praseodymium (Pr), erbium (Er), and ytterbium (Yb))-based SBL metal complexes was successfully synthesized, and their functional groups were elaborately demonstrated using UV-visible, Fourier transform infrared (FT-IR), and fluorescence spectroscopy analyses...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444929/development-and-external-validation-of-prediction-models-for-10-year-survival-of-invasive-breast-cancer-comparison-with-predict-and-cancermath
#11
Solon Karapanagiotis, Paul D P Pharoah, Christopher H Jackson, Paul J Newcombe
PURPOSE: To compare PREDICT and CancerMath, two widely used prognostic models for invasive breast cancer, taking into account their clinical utility. Furthermore, it is unclear whether these models could be improved. Experimental Design: A dataset of 5729 women was used for model development. A Bayesian variable selection algorithm was implemented to stochastically search for important interaction terms among the predictors. The derived models were then compared in three independent datasets (n = 5534)...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444670/breast-cancer-in-ethiopia-evidence-for-geographic-difference-in-the-distribution-of-molecular-subtypes-in-africa
#12
Endale Hadgu, Daniel Seifu, Wondemagegnhu Tigneh, Yonas Bokretsion, Abebe Bekele, Markos Abebe, Thomas Sollie, Sofia D Merajver, Christina Karlsson, Mats G Karlsson
BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2)...
February 14, 2018: BMC Women's Health
https://www.readbyqxmd.com/read/29443653/efficacy-of-chemotherapy-for-er-negative-and-er-positive-isolated-locoregional-recurrence-of-breast-cancer-final-analysis-of-the-calor-trial
#13
Irene L Wapnir, Karen N Price, Stewart J Anderson, André Robidoux, Miguel Martín, Johan W R Nortier, Alexander H G Paterson, Mothaffar F Rimawi, István Láng, José Manuel Baena-Cañada, Beat Thürlimann, Eleftherios P Mamounas, Charles E Geyer, Shari Gelber, Alan S Coates, Richard D Gelber, Priya Rastogi, Meredith M Regan, Norman Wolmark, Stefan Aebi
Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer...
February 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29441192/knockdown-of-lncrna-mapt-as1-inhibites-proliferation-and-migration-and-sensitizes-cancer-cells-to-paclitaxel-by-regulating-mapt-expression-in-er-negative-breast-cancers
#14
Yiyuan Pan, Yiqi Pan, Yue Cheng, Fan Yang, Zhihan Yao, Ouchen Wang
Background: MAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers. In this study, we investigated the role of MAPT-AS1 in the progression and paclitaxel resistance in breast cancer, and the regulation between MAPT-AS1 and its natural comparable sense transcripts MAPT. Methods: We analysed the breast cancer patients' clinical information and explored the function of MAPT-AS1 by gain- and loss-of function assays in vitro and in vivo...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29440915/effects-of-core-needle-biopsy-and-subsequent-neoadjuvant-chemotherapy-on-molecular-alterations-and-outcome-in-breast-cancer
#15
Lingmin Xie, Xiaolei Li, Qinchuan Wang, Jichun Zhou, Jun Shen, Lixi Luo, Yi Lu, Linbo Wang
Objectives: The aim of our study is to evaluate the effect of core needle biopsy (CNB) and subsequent neoadjuvant chemotherapy (NAC) on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth hormone receptor 2 (HER2) and Ki67 in breast cancer, and the associated influencing factors. Materials and methods: In this retrospective cohort study, 143 patients with primary operable breast cancer who received NAC were included. ER, PR, HER2 and Ki67 statuses were compared between pretreatment and posttreatment residual samples...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29440181/a-first-in-human-study-of-the-new-oral-selective-estrogen-receptor-degrader-azd9496-for-hr-her2-advanced-breast-cancer
#16
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P O Lindemann, Shethah Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
PURPOSE: AZD9496 is an oral non-steroidal, small-molecule inhibitor of estrogen receptor alpha (ERα), and a potent and selective antagonist and degrader of ERα. This first in human Phase 1 study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity. EXPERIMENTAL DESIGN: Forty-five patients received AZD9496 (20 mg once daily to 600 mg twice daily) in a dose-escalation, dose- expansion 'rolling 6' design...
February 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436674/the-targeted-inhibition-of-hsp90-by-a-synthetic-small-molecule-dpide-offers-an-effective-treatment-strategy-against-tnbcs
#17
Yong Jin Oh, Sun You Park, Young Ho Seo
Triple-negative breast cancers (TNBCs) are the most aggressive and metastatic subtype of breast cancers and exhibit poor clinical outcome due to the lack of drug target receptors such as estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (Her2). The limited effectiveness of therapeutic options and the poor prognosis of TNBC patients emphasize the urgent need for identifying new therapeutic agents. In this regard, heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of TNBCs...
February 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29436642/synergistic-anticancer-effects-of-ruxolitinib-and-calcitriol-in-estrogen-receptor%C3%A2-positive-human-epidermal-growth-factor-receptor-2%C3%A2-positive-breast-cancer-cells
#18
Seung Taek Lim, Ye Won Jeon, Hongki Gwak, Se Young Kim, Young Jin Suh
The Janus kinase (JAK)1 and JAK2 inhibitor, ruxolitinib, and the active form of vitamin D (calcitriol) were previously reported to possess anticancer effects in breast cancer. The present study investigated the combined effects of ruxolitinib and calcitriol on an estrogen receptor (ER)‑positive, human epidermal growth factor receptor 2 (HER2)‑positive, breast cancer cell line. The ER and HER2‑positive MCF7‑HER18 breast cancer cell line was used to investigate the combination effect of ruxolitinib and calcitriol...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436614/arctigenin-inhibits-the-activation-of-the-mtor-pathway-resulting-in-autophagic-cell-death-and-decreased-er-expression-in-er-positive-human-breast-cancer-cells
#19
Thressi Maxwell, Kyu Shik Lee, Soyoung Kim, Kyung-Soo Nam
Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer...
February 9, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29436393/therapeutically-targeting-tumor-microenvironment-mediated-drug-resistance-in-estrogen-receptor-positive-breast-cancer
#20
Kevin Shee, Wei Yang, John W Hinds, Riley A Hampsch, Frederick S Varn, Nicole A Traphagen, Kishan Patel, Chao Cheng, Nicole P Jenkins, Arminja N Kettenbach, Eugene Demidenko, Philip Owens, Anthony C Faber, Todd R Golub, Ravid Straussman, Todd W Miller
Drug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer. Phosphoproteomic analyses identified ERK1/2 as a major output of FGF2 signaling via FGF receptors (FGFRs), with consequent up-regulation of Cyclin D1 and down-regulation of Bim as mediators of drug resistance...
February 7, 2018: Journal of Experimental Medicine
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