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sherene loi

Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
Kathryn Alsop, Heather Thorne, Shahneen Sandhu, Anne Hamilton, Christopher Mintoff, Elizabeth Christie, Odette Spruyt, Scott Williams, Orla McNally, Linda Mileshkin, Sumitra Ananda, Julene Hallo, Sherene Loi, Clare Scott, Peter Savas, Lisa Devereux, Patricia O'Brien, Sameera Gunawardena, Clare Hampson, Kate Strachan, Rufaro Diana Jaravaza, Victoria Francis, Gregory Young, David Ranson, Ravindra Samaranayake, David Stevens, Samantha Boyle, Clare Fedele, Monique Topp, Gwo Ho, Zhi Ling Teo, Renea A Taylor, Melissa M Papargiris, Mitchell G Lawrence, Hong Wang, Gail P Risbridger, Nicole M Haynes, Mikolaj Medon, Ricky W Johnstone, Eva Vidacs, Gisela Mir Arnau, Ismael A Vergara, Anthony T Papenfuss, Grant McArthur, Paul Waring, Shirley Carvosso, Christopher Angel, David Gyorki, Benjamin Solomon, Gillian Mitchell, Sue Shanley, Prudence A Francis, Sarah-Jane Dawson, Amy Haffenden, Erin Tidball, Mila Volchek, Jan Pyman, Mohammed Madadin, Jodie Leditschke, Stephen Cordner, Mark Shackleton, David D Bowtell
No abstract text is available yet for this article.
October 2016: Nature Biotechnology
Silvia Darb-Esfahani, Carsten Denkert, Albrecht Stenzinger, Christoph Salat, Bruno Sinn, Christian Schem, Volker Endris, Peter Klare, Wolfgang Schmitt, Jens-Uwe Blohmer, Wilko Weichert, Markus Möbs, Hans Tesch, Sherko Kümmel, Peter Sinn, Christian Jackisch, Manfred Dietel, Toralf Reimer, Sherene Loi, Michael Untch, Gunter von Minckwitz, Valentina Nekljudova, Sibylle Loibl
BACKGROUND: TP53 mutations are frequent in breast cancer, however their clinical relevance in terms of response to chemotherapy is controversial. METHODS: 450 pre-therapeutic, formalin-fixed, paraffin-embedded core biopsies from the phase II neoadjuvant GeparSixto trial that included HER2-positive and triple negative breast cancer (TNBC) were subjected to Sanger sequencing of exons 5-8 of the TP53 gene. TP53 status was correlated to response to neoadjuvant anthracycline/taxane-based chemotherapy with or without carboplatin and trastuzumab/lapatinib in HER2-positive and bevacizumab in TNBC...
September 7, 2016: Oncotarget
Sunil Verma, Cynthia Huang Bartlett, Patrick Schnell, Angela M DeMichele, Sherene Loi, Jungsil Ro, Marco Colleoni, Hiroji Iwata, Nadia Harbeck, Massimo Cristofanilli, Ke Zhang, Alexandra Thiele, Nicholas C Turner, Hope S Rugo
BACKGROUND: Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. MATERIALS AND METHODS: Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo...
July 1, 2016: Oncologist
Carsten Denkert, Stephan Wienert, Audrey Poterie, Sibylle Loibl, Jan Budczies, Sunil Badve, Zsuzsanna Bago-Horvath, Anita Bane, Shahinaz Bedri, Jane Brock, Ewa Chmielik, Matthias Christgen, Cecile Colpaert, Sandra Demaria, Gert Van den Eynden, Giuseppe Floris, Stephen B Fox, Dongxia Gao, Barbara Ingold Heppner, S Rim Kim, Zuzana Kos, Hans H Kreipe, Sunil R Lakhani, Frederique Penault-Llorca, Giancarlo Pruneri, Nina Radosevic-Robin, David L Rimm, Stuart J Schnitt, Bruno V Sinn, Peter Sinn, Nicolas Sirtaine, Sandra A O'Toole, Giuseppe Viale, Koen Van de Vijver, Roland de Wind, Gunter von Minckwitz, Frederick Klauschen, Michael Untch, Peter A Fasching, Toralf Reimer, Karen Willard-Gallo, Stefan Michiels, Sherene Loi, Roberto Salgado
Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists...
October 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Charlotte Fribbens, Ben O'Leary, Lucy Kilburn, Sarah Hrebien, Isaac Garcia-Murillas, Matthew Beaney, Massimo Cristofanilli, Fabrice Andre, Sherene Loi, Sibylle Loibl, John Jiang, Cynthia Huang Bartlett, Maria Koehler, Mitch Dowsett, Judith M Bliss, Stephen R D Johnston, Nicholas C Turner
PURPOSE: ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. MATERIALS AND METHODS: In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Mariam Mansour, Sue Haupt, Ai-Leen Chan, Nathan Godde, Alexandra Rizzitelli, Sherene Loi, Franco Caramia, Siddhartha Deb, Elena A Takano, Mark Bishton, Cameron Johnstone, Brendon Monahan, Yarra Levav-Cohen, Yong-Hui Jiang, Alpha S Yap, Stephen Fox, Ora Bernard, Robin Anderson, Ygal Haupt
Metastatic disease is the major cause of breast cancer-related death and despite many advances, current therapies are rarely curative. Tumor cell migration and invasion require actin cytoskeletal reorganization to endow cells with capacity to disseminate and initiate the formation of secondary tumors. However, it is still unclear how these migratory cells colonize distant tissues to form macrometastases. The E6-associated protein, E6AP, acts both as an E3 ubiquitin-protein ligase and as a coactivator of steroid hormone receptors...
July 15, 2016: Cancer Research
Deepak Mittal, Debottam Sinha, Deborah Barkauskas, Arabella Young, Murugan Kalimutho, Kimberley Stannard, Franco Caramia, Benjamin Haibe-Kains, John Stagg, Kum Kum Khanna, Sherene Loi, Mark J Smyth
Adenosine plays an important role in inflammation and tumor development, progression, and responses to therapy. We show that an adenosine 2B receptor inhibitor (A2BRi) decreases both experimental and spontaneous metastasis and combines with chemotherapy or immune checkpoint inhibitors in mouse models of melanoma and triple-negative breast cancer (TNBC) metastasis. Decreased metastasis upon A2BR inhibition is independent of host A2BR and lymphocytes and myeloid cells. Knockdown of A2BR on mouse and human cancer cells reduces their metastasis in vivo and decreases their viability and colony-forming ability, while transiently delaying cell-cycle arrest in vitro The prometastatic activity of adenosine is partly tumor A2BR dependent and independent of host A2BR expression...
August 1, 2016: Cancer Research
Renata Duchnowska, Rafał Pęksa, Barbara Radecka, Tomasz Mandat, Tomasz Trojanowski, Bożena Jarosz, Bogumiła Czartoryska-Arłukowicz, Wojciech P Olszewski, Waldemar Och, Ewa Kalinka-Warzocha, Wojciech Kozłowski, Anna Kowalczyk, Sherene Loi, Wojciech Biernat, Jacek Jassem
BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment...
2016: Breast Cancer Research: BCR
Sherene Loi, Urania Dafni, Dimitris Karlis, Varvara Polydoropoulou, Brandon M Young, Scooter Willis, Bradley Long, Evandro de Azambuja, Christos Sotiriou, Giuseppe Viale, Josef Rüschoff, Martine J Piccart, Mitch Dowsett, Stefan Michiels, Brian Leyland-Jones
IMPORTANCE: A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown. OBJECTIVE: To determine the magnitude of trastuzumab benefit according to quantitative levels of ER and HER2 in the HERceptin Adjuvant (HERA) trial. DESIGN, SETTING, AND PARTICIPANTS: The HERA trial was an international, multicenter, randomized trial that included 5099 patients with early-stage HER2-positive breast cancer, randomized between 2001 and 2005 to receive either no trastuzumab or trastuzumab, after adjuvant chemotherapy...
August 1, 2016: JAMA Oncology
Jane Beith, Katie Burslem, Richard Bell, Natasha Woodward, Nicole McCarthy, Richard De Boer, Sherene Loi, Andrew Redfern
Endocrine therapy for the treatment of hormone receptor positive, HER2 negative, metastatic breast cancer is continually evolving. We systematically reviewed phase 2 and 3 randomized controlled trials (RCTs) of agents used in this setting to assess the effectiveness and safety of these agents for postmenopausal women. Across the 32 studies in more than 10,000 patients, the greatest improvement in progression-free survival (PFS) was seen with the addition of a cyclin-dependent kinase (CDK)4/6 inhibitor to standard endocrine therapy...
March 2016: Asia-Pacific Journal of Clinical Oncology
Massimo Cristofanilli, Nicholas C Turner, Igor Bondarenko, Jungsil Ro, Seock-Ah Im, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Sunil Verma, Hiroji Iwata, Nadia Harbeck, Ke Zhang, Kathy Puyana Theall, Yuqiu Jiang, Cynthia Huang Bartlett, Maria Koehler, Dennis Slamon
BACKGROUND: In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses...
April 2016: Lancet Oncology
Shin Foong Ngiow, Sherene Loi, David Thomas, Mark J Smyth
Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials...
2016: Advances in Immunology
Chee Khoon Lee, Lucy Davies, Val J Gebski, Sarah J Lord, Angelo Di Leo, Stephen Johnston, Charles Geyer, David Cameron, Michael F Press, Catherine Ellis, Sherene Loi, Ian Marschner, John Simes, Paul de Souza
PURPOSE: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. PATIENTS AND METHODS: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS)...
March 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Sherene Loi, Peter Savas
No abstract text is available yet for this article.
February 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Deepak Mittal, Franco Caramia, Stefan Michiels, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Christos Sotiriou, Sherene Loi, Mark J Smyth
The HER2/ErbB2 monoclonal antibody (mAb) trastuzumab is combined with chemotherapy as a standard-of-care for newly diagnosed HER2(+) breast cancer patients, but some patients treated with this combination therapy experience early relapse. Our analysis of data from a clinical trial evaluating the efficacy of chemotherapy plus/minus trastuzumab suggested that the magnitude of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy...
January 15, 2016: Cancer Research
Peter Savas, Roberto Salgado, Carsten Denkert, Christos Sotiriou, Phillip K Darcy, Mark J Smyth, Sherene Loi
The clinical relevance of the host immune system in breast cancer has long been unexplored. Studies developed over the past decade have highlighted the biological heterogeneity of breast cancer, prompting researchers to investigate whether the role of the immune system in this malignancy is similar across different molecular subtypes of the disease. The presence of high levels of lymphocytic infiltration has been consistently associated with a more-favourable prognosis in patients with early stage triple-negative and HER2-positive breast cancer...
April 2016: Nature Reviews. Clinical Oncology
Sherene Loi, Sathana Dushyanthen, Paul A Beavis, Roberto Salgado, Carsten Denkert, Peter Savas, Susan Combs, David L Rimm, Jennifer M Giltnane, Monica V Estrada, Violeta Sánchez, Melinda E Sanders, Rebecca S Cook, Mark A Pilkinton, Simon A Mallal, Kai Wang, Vincent A Miller, Phil J Stephens, Roman Yelensky, Franco D Doimi, Henry Gómez, Sergey V Ryzhov, Phillip K Darcy, Carlos L Arteaga, Justin M Balko
PURPOSE: Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking. EXPERIMENTAL DESIGN: We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer...
March 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Paul A Beavis, Clare Y Slaney, Nicole Milenkovski, Melissa A Henderson, Sherene Loi, John Stagg, Michael H Kershaw, Phillip K Darcy
In our recent study, we show that tumoral CD73 expression limits the efficacy of anti-PD-1 therapy, and this is rescued by concomitant A2A blockade. Since CD73 is known to be overexpressed in several human cancers and A2A antagonists have undergone clinical trials for Parkinson's Disease, this combination warrants further investigation.
November 2015: Oncoimmunology
Amir Sonnenblick, Sylvain Brohée, Debora Fumagalli, Françoise Rothé, Delphine Vincent, Michael Ignatiadis, Christine Desmedt, Roberto Salgado, Nicolas Sirtaine, Sherene Loi, Patrick Neven, Sibylle Loibl, Carsten Denkert, Heikki Joensuu, Martine Piccart, Christos Sotiriou
Trastuzumab is a remarkably effective therapy for patients with human epidermal growth factor receptor 2 (HER2)--positive breast cancer (BC). However, not all women with high levels of HER2 benefit from trastuzumab. By integrating mRNA and protein expression data from Reverse-Phase Protein Array Analysis (RPPA) in HER2-positive BC, we developed gene expression metagenes that reflect pathway activation levels. Next we assessed the ability of these metagenes to predict resistance to adjuvant trastuzumab using gene expression data from two independent datasets...
October 6, 2015: Oncotarget
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