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https://www.readbyqxmd.com/read/29559561/safety-and-antitumor-activity-of-pembrolizumab-in-patients-with-estrogen-receptor%C3%A2-positive-human-epidermal-growth-factor-receptor-2%C3%A2-negative-advanced-breast-cancer
#1
Hope S Rugo, Jean-Pierre Delord, Seock-Ah Im, Patrick A Ott, Sarina A Piha-Paul, Phillipe L Bedard, Jasgit Sachev, Christophe Le Tourneau, Emilie M J van Brummelen, Andreea Varga, Roberto Salgado, Sherene Loi, Sanatan Saraf, Dina Pietrangelo, Vassiliki Karantza, Antoinette R Tan
PURPOSE: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor‒positive (ER+)/human epidermal growth factor receptor 2-negative (HER2- ) advanced breast cancer with programmed death ligand 1‒positive (PD-L1‒positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. EXPERIMENTAL DESIGN: Patients with ER+/HER2- advanced breast cancer with PD-L1‒positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29471435/immune-infiltration-in-invasive-lobular-breast-cancer
#2
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
#3
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/29445373/tissue-dependent-tumor-microenvironments-and-their-impact-on-immunotherapy-responses
#4
REVIEW
Amanda J Oliver, Peter K H Lau, Ashleigh S Unsworth, Sherene Loi, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
Recent advances in cancer immunology have led to a better understanding of the role of the tumor microenvironment (TME) in tumor initiation, progression, and metastasis. Tumors can occur at many locations within the body and coevolution between malignant tumor cells and non-malignant cells sculpts the TME at these sites. It has become increasingly clear that there are specific differences of the TMEs at different anatomical locations, and these tissue-specific TMEs regulate tumor growth, determine metastatic progression, and impact on the outcome of therapy responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29420467/her-kinase-inhibition-in-patients-with-her2-and-her3-mutant-cancers
#5
David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger, Ingrid A Mayer, Valentina Boni, Emiliano Calvo, Sherene Loi, Albert C Lockhart, Joseph P Erinjeri, Maurizio Scaltriti, Gary A Ulaner, Juber Patel, Jiabin Tang, Hannah Beer, S Duygu Selcuklu, Aphrothiti J Hanrahan, Nancy Bouvier, Myra Melcer, Rajmohan Murali, Alison M Schram, Lillian M Smyth, Komal Jhaveri, Bob T Li, Alexander Drilon, James J Harding, Gopa Iyer, Barry S Taylor, Michael F Berger, Richard E Cutler, Feng Xu, Anna Butturini, Lisa D Eli, Grace Mann, Cynthia Farrell, Alshad S Lalani, Richard P Bryce, Carlos L Arteaga, Funda Meric-Bernstam, José Baselga, David B Solit
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials...
February 8, 2018: Nature
https://www.readbyqxmd.com/read/29233560/tumour-infiltrating-lymphocytes-in-breast-cancer-increasing-clinical-relevance
#6
Roberto Salgado, Sherene Loi
No abstract text is available yet for this article.
January 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29156891/investigating-the-role-of-tumor-infiltrating-lymphocytes-in-advanced-her2-positive-breast-cancer
#7
EDITORIAL
Stephen J Luen, Sherene Loi
No abstract text is available yet for this article.
November 14, 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29061314/tumor-infiltrating-lymphocytes-in-breast-cancer-and-implications-for-clinical-practice
#8
REVIEW
Debora de Melo Gagliato, Javier Cortes, Giuseppe Curigliano, Sherene Loi, Carsten Denkert, Jose Perez-Garcia, Esther Holgado
Breast Cancer (BC) can be classified using pathologic features, such as grade and tumor size. It can be categorized based on the gene expression profile, which identifies the distinct molecular subtype. More recently, stromal tissue has been recognized as an important modulator of tumor cell growth, pathogenesis, and progression. Immune cells could drive important clinical characteristics that affect BC outcomes. Subgroups of patients who have tumor-infiltrating lymphocytes in the stroma may have better response to chemotherapy and favorable long-term prognosis...
October 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29024776/update-on-tumor-infiltrating-lymphocytes-tils-in-breast-cancer-including-recommendations-to-assess-tils-in-residual-disease-after-neoadjuvant-therapy-and-in-carcinoma-in-situ-a-report-of-the-international-immuno-oncology-biomarker-working-group-on-breast-cancer
#9
REVIEW
Maria Vittoria Dieci, Nina Radosevic-Robin, Susan Fineberg, Gert van den Eynden, Nils Ternes, Frederique Penault-Llorca, Giancarlo Pruneri, Timothy M D'Alfonso, Sandra Demaria, Carlos Castaneda, Joselyn Sanchez, Sunil Badve, Stefan Michiels, Veerle Bossuyt, Federico Rojo, Baljit Singh, Torsten Nielsen, Giuseppe Viale, Seong-Rim Kim, Stephen Hewitt, Stephan Wienert, Sybille Loibl, David Rimm, Fraser Symmans, Carsten Denkert, Sylvia Adams, Sherene Loi, Roberto Salgado
Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research...
October 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28947417/combined-cdk4-6-and-pi3k%C3%AE-inhibition-is-synergistic-and-immunogenic-in-triple-negative-breast-cancer
#10
Zhi Ling Teo, Stephanie Versaci, Sathana Dushyanthen, Franco Caramia, Peter Savas, Chris P Mintoff, Magnus Zethoven, Balaji Virassamy, Stephen J Luen, Grant A McArthur, Wayne A Phillips, Phillip K Darcy, Sherene Loi
New treatments for triple-negative breast cancer (TNBC) are urgently needed. Despite there being little evidence of clinical activity as single-agent therapies, we show that dual blockade of PI3Kα and CDK4/6 is synergistically effective against multiple RB1 -wild-type TNBC models. Combined PI3Kα and CDK4/6 inhibition significantly increased apoptosis, cell-cycle arrest, and tumor immunogenicity and generated immunogenic cell death in human TNBC cell lines. Combination treatment also significantly improved disease control in human xenograft models compared with either monotherapy...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#11
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923573/neoadjuvant-buparlisib-plus-trastuzumab-and-paclitaxel-for-women-with-her2-primary-breast-cancer-a-randomised-double-blind-placebo-controlled-phase-ii-trial-neophoebe
#12
RANDOMIZED CONTROLLED TRIAL
Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee, Sabine Turri, Patrick Urban, Sherko Kümmel, Guenther Steger, Andrea Gombos, Michael Lux, Martine J Piccart, Gunter Von Minckwitz, José Baselga, Sherene Loi
AIM: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer. METHODS: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28855210/cd73-promotes-resistance-to-her2-erbb2-antibody-therapy
#13
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/28777143/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immuno-oncology-biomarkers-working-group-part-2-tils-in-melanoma-gastrointestinal-tract-carcinomas-non
#14
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma...
November 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28777142/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immunooncology-biomarkers-working-group-part-1-assessing-the-host-immune-response-tils-in-invasive-breast
#15
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment...
September 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#16
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
August 2017: Lancet Oncology
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
#17
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/28668293/mechanisms-of-resistance-of-chemotherapy-in-early-stage-triple-negative-breast-cancer-tnbc
#18
Lironne Wein, Sherene Loi
Triple negative breast cancer (TNBC) a clinically aggressive subtype of breast cancer with poor outcomes. Chromosomal instability is a hallmark of many TNBCs, and likely underlies its ability to adapt and rapidly become resistant to chemotherapy. A study of residual disease after neoadjuvant chemotherapy have identified biological mechanisms driving this resistance to chemotherapy. Copy number amplifications such as MCL1, MYC and JAK2, as well as PTEN deletions or mutations have all been identified at a higher frequency in residual disease, suggesting they may play a role in de novo or acquired chemotherapy resistance...
August 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28652278/palbociclib-combined-with-fulvestrant-in-premenopausal-women-with-advanced-breast-cancer-and-prior-progression-on-endocrine-therapy-paloma-3-results
#19
Sibylle Loibl, Nicholas C Turner, Jungsil Ro, Massimo Cristofanilli, Hiroji Iwata, Seock-Ah Im, Norikazu Masuda, Sherene Loi, Fabrice André, Nadia Harbeck, Sunil Verma, Elizabeth Folkerd, Kathy Puyana Theall, Justin Hoffman, Ke Zhang, Cynthia Huang Bartlett, Mitchell Dowsett
BACKGROUND: The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). PATIENTS AND METHODS: One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo...
September 2017: Oncologist
https://www.readbyqxmd.com/read/28592566/combined-immune-checkpoint-blockade-as-a-therapeutic-strategy-for-brca1-mutated-breast-cancer
#20
Emma Nolan, Peter Savas, Antonia N Policheni, Phillip K Darcy, François Vaillant, Christopher P Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B Pang, Stephen B Fox, Charles M Perou, Jane E Visvader, Daniel H D Gray, Sherene Loi, Geoffrey J Lindeman
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1 -associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1 -deficient tumor model...
June 7, 2017: Science Translational Medicine
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