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https://www.readbyqxmd.com/read/29662649/-18-fdg-pet-ct-and-molecular-markers-to-predict-response-to-neoadjuvant-chemotherapy-and-outcome-in-her2-negative-advanced-luminal-breast-cancers-patients
#1
Patricia de Cremoux, Lucie Biard, Brigitte Poirot, Philippe Bertheau, Luis Teixeira, Jacqueline Lehmann-Che, Fatiha A Bouhidel, Pascal Merlet, Marc Espié, Matthieu Resche-Rigon, Christos Sotiriou, David Groheux
Background: The efficacy of neoadjuvant chemotherapy regimens in advanced luminal breast cancer patients is difficult to predict. Intrinsic properties of breast tumors, including altered gene expression profile and dynamic evaluation of metabolic properties of tumor cells using positron emission tomography/computed tomography (PET/CT) of tumor cells, have been identified to guide patient's prognosis. The aim of this study is to determine if both analyses may improve the prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative breast cancers (BCs) patients...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29616304/tumor-metabolism-assessed-by-fdg-pet-ct-and-tumor-proliferation-assessed-by-genomic-grade-index-to-predict-response-to-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#2
David Groheux, L Biard, J Lehmann-Che, L Teixeira, F A Bouhidel, B Poirot, P Bertheau, P Merlet, M Espié, M Resche-Rigon, C Sotiriou, P de Cremoux
PURPOSE: Survival is increased when pathological complete response (pCR) is reached after neoadjuvant chemotherapy (NAC), especially in triple-negative breast cancer (TNBC) patients. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) and the genomic grade index (GGI), each separately, showed good potential to predict pCR. Our study was designed to evaluate the predictive value for the therapeutic response of a combination of parameters based on FDG-PET, histoclinical features and molecular markers of proliferation...
April 4, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29471435/immune-infiltration-in-invasive-lobular-breast-cancer
#3
Christine Desmedt, Roberto Salgado, Marco Fornili, Giancarlo Pruneri, Gert Van den Eynden, Gabriele Zoppoli, Françoise Rothé, Laurence Buisseret, Soizic Garaud, Karen Willard-Gallo, David Brown, Yacine Bareche, Ghizlane Rouas, Christine Galant, François Bertucci, Sherene Loi, Giuseppe Viale, Angelo Di Leo, Andrew R Green, Ian O Ellis, Emad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou
Background: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. Methods: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC)...
February 20, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29470143/tumor-pik3ca-genotype-and-prognosis-in-early-stage-breast-cancer-a-pooled-analysis-of-individual-patient-data
#4
Dimitrios Zardavas, Luc Te Marvelde, Roger L Milne, Debora Fumagalli, George Fountzilas, Vassiliki Kotoula, Evangelia Razis, George Papaxoinis, Heikki Joensuu, Mary Ellen Moynahan, Bryan T Hennessy, Ivan Bieche, Lao H Saal, Olle Stal, Barry Iacopetta, Jeanette Dupont Jensen, Sandra O'Toole, Elena Lopez-Knowles, Mattia Barbaraeschi, Shinzaburo Noguchi, Hatem A Azim, Enrique Lerma, Thomas Bachelot, Qing Wang, Gizeh Perez-Tenorio, Cornelis J H Can de Velde, Daniel W Rea, Vicky Sabine, John M S Bartlett, Christos Sotiriou, Stefan Michiels, Sherene Loi
Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study...
February 22, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29436103/genomic-hotspots-but-few-recurrent-fusion-genes-in-breast-cancer
#5
Danai Fimereli, Debora Fumagalli, David Brown, David Gacquer, Françoise Rothé, Roberto Salgado, Denis Larsimont, Christos Sotiriou, Vincent Detours
The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations...
February 13, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29428479/immuno-oncology-101-overview-of-major-concepts-and-translational-perspectives
#6
REVIEW
B Allard, S Aspeslagh, S Garaud, F A Dupont, C Solinas, M Kok, B Routy, C Sotiriou, J Stagg, L Buisseret
Cancer immunotherapy is demonstrating impressive clinical benefit in different malignancies and clinical oncologists are increasingly turning their attention to immune-oncology. It is now well recognized that innate and adaptive immune cells infiltrating tumors are associated with clinical outcomes and responses to treatments, and can be harnessed to patients' benefit. Considerable advances have also been made in understanding how cancers escape from immune attack. Targeting of immunological escape processes regulated by the expression of immune checkpoint receptors and ligands and the down-modulation of tumor antigen presentation is the basis of immuno-oncology treatments...
February 8, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29365031/unravelling-triple-negative-breast-cancer-molecular-heterogeneity-using-an-integrative-multiomic-analysis
#7
Y Bareche, D Venet, M Ignatiadis, P Aftimos, M Piccart, F Rothe, C Sotiriou
Background: Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple negative breast cancers (TNBCs) reporting, at least 6 different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each subtype, their difference in survival and response to therapy...
January 22, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29314288/the-limitations-of-dermoscopy-false-positive-and-false-negative-tumours
#8
REVIEW
V Papageorgiou, Z Apalla, E Sotiriou, C Papageorgiou, E Lazaridou, S Vakirlis, D Ioannides, A Lallas
Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumours, improving their ability to detect skin cancer and better recognize benign moles. However, dermoscopically 'false-positive' and 'false-negative' tumours do exist. False-positive diagnosis usually leads to unnecessary excisions. False-negative diagnosis is much more dangerous, as it might result in overlooking a cancer, with severe undesirable consequences for the patient and the physician. Therefore, management strategies should mainly focus on addressing the risk of dermoscopically false-negative tumours...
January 5, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29278737/network-science-in-clinical-trials-a-patient-centered-approach
#9
REVIEW
Venkata S K Manem, Roberto Salgado, Philippe Aftimos, Christos Sotiriou, Benjamin Haibe-Kains
There has been a paradigm shift in translational oncology with the advent of novel molecular diagnostic tools in the clinic. However, several challenges are associated with the integration of these sophisticated tools into clinical oncology and daily practice. High-throughput profiling at the DNA, RNA and protein levels (omics) generate a massive amount of data. The analysis and interpretation of these is non-trivial but will allow a more thorough understanding of cancer. Linear modelling of the data as it is often used today is likely to limit our understanding of cancer as a complex disease, and at times under-performs to capture a phenotype of interest...
December 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29207087/p-stat3-in-luminal-breast-cancer-integrated-rna-protein-pooled-analysis-and-results-from-the-big-2-98-phase-iii-trial
#10
Amir Sonnenblick, Roberto Salgado, Sylvain Brohée, Tamar Zahavi, Tamar Peretz, Gert Van den Eynden, Ghizlane Rouas, Asher Salmon, Prudence A Francis, Angelo Di Leo, John P A Crown, Giuseppe Viale, Laura Daly, Bahar Javdan, Sho Fujisawa, Evandro De Azambuja, Ameye Lieveke, Martine J Piccart, Jacqueline F Bromberg, Christos Sotiriou
In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29177149/basal-cell-carcinoma-in-a-childhood-cancer-survivor-what-neurosurgeons-should-avoid
#11
Zoe Apalla, Eleni Sotiriou, Aimilios Lallas, Elizabeth Lazaridou, Efstratios Vakirlis, Demetrios Ioannides
Among childhood cancer survivors (CCSs), non-melanoma skin cancer (NMSC) is the most common type of second malignancy. Morbidity related to the development of NMSC in this group of patients may be sometimes unpredictable and difficult to manage. We present the case of a 49-year-old female who was a CCS and developed giant superficial basal cell carcinomas (sBCCs) over the previously irradiated field of the scalp. BCC involved the atrophic skin overlying the catheter of the peritoneal cerebral shunt that was set there for the management of hydrocephalus...
October 2017: Skin Appendage Disorders
https://www.readbyqxmd.com/read/29145561/clinical-significance-of-cd73-in-triple-negative-breast-cancer-multiplex-analysis-of-a-phase-iii-clinical-trial
#12
L Buisseret, S Pommey, B Allard, S Garaud, M Bergeron, I Cousineau, L Ameye, Y Bareche, M Paesmans, J P A Crown, A Di Leo, S Loi, M Piccart-Gebhart, K Willard-Gallo, C Sotiriou, J Stagg
Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29096156/recurrence-dynamics-of-breast-cancer-according-to-baseline-body-mass-index
#13
RANDOMIZED CONTROLLED TRIAL
Elia Biganzoli, Christine Desmedt, Marco Fornili, Evandro de Azambuja, Nathalie Cornez, Fernand Ries, Marie-Thérèse Closon-Dejardin, Joseph Kerger, Christian Focan, Angelo Di Leo, Jean-Marie Nogaret, Christos Sotiriou, Martine Piccart, Romano Demicheli
BACKGROUND: In cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy...
December 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29077781/a-gene-signature-to-predict-high-tumor-infiltrating-lymphocytes-after-neoadjuvant-chemotherapy-and-outcome-in-patients-with-triple-negative-breast-cancer
#14
C Criscitiello, M A Bayar, G Curigliano, F W Symmans, C Desmedt, H Bonnefoi, B Sinn, G Pruneri, C Vicier, J Y Pierga, C Denkert, S Loibl, C Sotiriou, S Michiels, F André
Background: In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pretreatment samples to predict the extent of TILs after NACT and then to test its prognostic value on survival. Patients and methods: Using 99 pretreatment samples, we generated a four-gene signature associated with high post-NACT TILs...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28855210/cd73-promotes-resistance-to-her2-erbb2-antibody-therapy
#15
Martin Turcotte, David Allard, Deepak Mittal, Yacine Bareche, Laurence Buisseret, Vinu José, Sandra Pommey, Vincent Delisle, Sherene Loi, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Christos Sotiriou, Mark J Smyth, John Stagg
Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810143/genomic-evolution-of-breast-cancer-metastasis-and-relapse
#16
Lucy R Yates, Stian Knappskog, David Wedge, James H R Farmery, Santiago Gonzalez, Inigo Martincorena, Ludmil B Alexandrov, Peter Van Loo, Hans Kristian Haugland, Peer Kaare Lilleng, Gunes Gundem, Moritz Gerstung, Elli Pappaemmanuil, Patrycja Gazinska, Shriram G Bhosle, David Jones, Keiran Raine, Laura Mudie, Calli Latimer, Elinor Sawyer, Christine Desmedt, Christos Sotiriou, Michael R Stratton, Anieta M Sieuwerts, Andy G Lynch, John W Martens, Andrea L Richardson, Andrew Tutt, Per Eystein Lønning, Peter J Campbell
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28714863/dna-methylation-based-immune-response-signature-improves-patient-diagnosis-in-multiple-cancers
#17
Jana Jeschke, Martin Bizet, Christine Desmedt, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Alexander Koch, Denis Larsimont, Roberto Salgado, Gert Van den Eynden, Karen Willard Gallo, Gianluca Bontempi, Matthieu Defrance, Christos Sotiriou, François Fuks
BACKGROUND: The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS: MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28685159/the-aurora-pilot-study-for-molecular-screening-of-patients-with-advanced-breast-cancer-a-study-of-the-breast-international-group
#18
Marion Maetens, David Brown, Alexandre Irrthum, Philippe Aftimos, Giuseppe Viale, Sibylle Loibl, Jean-François Laes, Peter J Campbell, Alastair Thompson, Javier Cortes, Sabine Seiler, Sara Vinnicombe, Mafalda Oliveira, Françoise Rothé, Yacine Bareche, Debora Fumagalli, Dimitrios Zardavas, Christine Desmedt, Martine Piccart, Sherene Loi, Christos Sotiriou
Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28673354/the-footprint-of-the-ageing-stroma-in-older-patients-with-breast-cancer
#19
Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers
BACKGROUND: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28621322/reliability-of-tumor-infiltrating-lymphocyte-and-tertiary-lymphoid-structure-assessment-in-human-breast-cancer
#20
Laurence Buisseret, Christine Desmedt, Soizic Garaud, Marco Fornili, Xiaoxiao Wang, Gert Van den Eyden, Alexandre de Wind, Sebastien Duquenne, Anais Boisson, Celine Naveaux, Francoise Rothé, Sandrine Rorive, Christine Decaestecker, Denis Larsimont, Martine Piccart-Gebhart, Elia Biganzoli, Christos Sotiriou, Karen Willard-Gallo
The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells...
September 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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