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1. What factors influence cellular pathologists’ confidence in case reporting?

Author

Evans, Harriet, Kimani, Peter K., Hiller, Louise, Tsang, Yee Wah, Sah, Shatrughan, Gopalakrishnan, Kishore, Boyd, Clinton, Loughrey, Maurice B., Kelly, Paul J., Boyle, David P., Clark, David, Ellis, Ian O., Ilyas, Mohammad, Rakha, Emad, Bickers, Adam, Roberts, Ian S. D., Soares, Maria F., Neil, Desley A. H., Dunn, Janet A., Azam, Ayesha, and Snead, David

Published
2024
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3. Optimising the diagnostic accuracy of First post-contrAst SubtracTed breast MRI (FAST MRI) through interpretation-training: a multicentre e-learning study, mapping the learning curve of NHS Breast Screening Programme (NHSBSP) mammogram readers using an enriched dataset

Author

Jones, Lyn I., Marshall, Andrea, Geach, Rebecca, Elangovan, Premkumar, O’Flynn, Elizabeth, Timlin, Tony, McKeown-Keegan, Sadie, Rose, Janice, Vinnicombe, Sarah, Taylor-Phillips, Sian, Halling-Brown, Mark, and Dunn, Janet A.

Published
2024
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4. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

Author

Yau, Christina, Osdoit, Marie, van der Noordaa, Marieke, Shad, Sonal, Wei, Jane, de Croze, Diane, Hamy, Anne-Sophie, Laé, Marick, Reyal, Fabien, Sonke, Gabe S, Steenbruggen, Tessa G, van Seijen, Maartje, Wesseling, Jelle, Martín, Miguel, Del Monte-Millán, Maria, López-Tarruella, Sara, I-SPY 2 Trial Consortium, Boughey, Judy C, Goetz, Matthew P, Hoskin, Tanya, Gould, Rebekah, Valero, Vicente, Edge, Stephen B, Abraham, Jean E, Bartlett, John MS, Caldas, Carlos, Dunn, Janet, Earl, Helena, Hayward, Larry, Hiller, Louise, Provenzano, Elena, Sammut, Stephen-John, Thomas, Jeremy S, Cameron, David, Graham, Ashley, Hall, Peter, Mackintosh, Lorna, Fan, Fang, Godwin, Andrew K, Schwensen, Kelsey, Sharma, Priyanka, DeMichele, Angela M, Cole, Kimberly, Pusztai, Lajos, Kim, Mi-Ok, van 't Veer, Laura J, Esserman, Laura J, and Symmans, W Fraser

Subjects
I-SPY 2 Trial Consortium, Humans, Breast Neoplasms, Neoplasm, Residual, Receptor, erbB-2, Chemotherapy, Adjuvant, Neoadjuvant Therapy, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Young Adult, Receptor, ErbB-2, Breast Cancer, Patient Safety, Clinical Research, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrevious studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.MethodsIn this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype.FindingsWe analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41-1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79-2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p

Published
2022

5. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Author

Escala-Garcia, Maria, Abraham, Jean, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Ashworth, Alan, Auer, Paul L, Auvinen, Päivi, Beckmann, Matthias W, Beesley, Jonathan, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Caldas, Carlos, Canzian, Federico, Chang-Claude, Jenny, Chanock, Stephen J, Chin, Suet-Feung, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Dunn, Janet A, Dunning, Alison M, Dwek, Miriam, Earl, Helena M, Eccles, Diana M, Eliassen, A Heather, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, George, Angela, Giles, Graham G, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Guo, Qi, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Harrington, Patricia A, Hiller, Louise, Hooning, Maartje J, Hopper, John L, Howell, Anthony, Huang, Chiun-Sheng, Huang, Guanmengqian, Hunter, David J, Jakubowska, Anna, John, Esther M, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Kitahara, Cari M, Koppert, Linetta B, Kraft, Peter, Kristensen, Vessela N, Lambrechts, Diether, Le Marchand, Loic, Lejbkowicz, Flavio, Lindblom, Annika, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Milne, Roger L, Mulligan, Anna Marie, Neuhausen, Susan L, Nevanlinna, Heli, Newman, William G, Olshan, Andrew F, Olson, Janet E, and Olsson, Håkan

Subjects
Germ Cells, Humans, Breast Neoplasms, GTP-Binding Protein alpha Subunits, GTP-Binding Protein alpha Subunits, Gq-G11, Receptors, Estrogen, Prognosis, Computational Biology, Signal Transduction, Apoptosis, Genotype, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Circadian Clocks, Gq-G11, Receptors, Estrogen, Cancer, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies
Abstract

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.

Published
2020

6. Computational approaches to support comparative analysis of multiparametric tests: Modelling versus Training

Author

Bartlett, John MS, Bayani, Jane, Kornaga, Elizabeth N, Danaher, Patrick, Crozier, Cheryl, Piper, Tammy, Yao, Cindy Q, Dunn, Janet A, Boutros, Paul C, and Stein, Robert C

Subjects
Health Services and Systems, Health Sciences, Health Services, Breast Cancer, Clinical Research, Cancer, Prevention, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Breast Neoplasms, Computer Simulation, Cost-Benefit Analysis, Female, Gene Expression Profiling, Genomics, Humans, Prognosis, Randomized Controlled Trials as Topic, OPTIMA Trial Management Group, General Science & Technology
Abstract

Multiparametric assays for risk stratification are widely used in the management of breast cancer, with applications being developed for a number of other cancer settings. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. There is an increasing need for robust methods to support cost effective comparisons of test performance in multiple settings. The derivation of similar risk classifications using genes comprising the following multi-parametric tests Oncotype DX® (Genomic Health.), Prosigna™ (NanoString Technologies, Inc.), MammaPrint® (Agendia Inc.) was performed using different computational approaches. Results were compared to the actual test results. Two widely used approaches were applied, firstly computational "modelling" of test results using published algorithms and secondly a "training" approach which used reference results from the commercially supplied tests. We demonstrate the potential for errors to arise when using a "modelling" approach without reference to real world test results. Simultaneously we show that a "training" approach can provide a highly cost-effective solution to the development of real-world comparisons between different multigene signatures. Comparisons between existing multiparametric tests is challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. We present an approach, modelled in breast cancer, which can provide health care providers and researchers with the potential to perform robust and meaningful comparisons between multigene tests in a cost-effective manner. We demonstrate that whilst viable estimates of gene signatures can be derived from modelling approaches, in our study using a training approach allowed a close approximation to true signature results.

Published
2020

7. Genome-wide association study of germline variants and breast cancer-specific mortality.

Author

Escala-Garcia, Maria, Guo, Qi, Dörk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K, Wang, Qin, Abraham, Jean, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W, Brucker, Sara Y, Burwinkel, Barbara, Caldas, Carlos, Caldés, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L, NBCS Collaborators, Cordina-Duverger, Emilie, Couch, Fergus J, Cox, David G, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dunn, Janet A, Dunning, Alison M, Durcan, Lorraine, Dwek, Miriam, Earl, Helena M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, George, Angela, Georgoulias, Vassilios, Giles, Graham G, Glendon, Gord, Goldgar, David E, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F, Harrington, Patricia A, Hart, Steven N, Hartikainen, Jaana M, Hein, Alexander, Hillemanns, Peter, Hiller, Louise, and Holleczek, Bernd

Subjects
NBCS Collaborators, Chromosomes, Human, Pair 7, Humans, Breast Neoplasms, Receptors, Estrogen, Prognosis, Proportional Hazards Models, Bayes Theorem, Female, Genetic Variation, Genome-Wide Association Study, White People, Genetics, Breast Cancer, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundWe examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.MethodsMeta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).ResultsWe did not find any variant associated with breast cancer-specific mortality at P

Published
2019

9. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients

Author

Adamson, Kathi, Albain, Kathy S., Asare, Adam L., Asare, Smita M., Balassanian, Ron, Beckwith, Heather, Berry, Scott M., Berry, Donald A., Boughey, Judy C., Buxton, Meredith B., Chen, Yunn-Yi, Chen, Beiyun, Chien, A. Jo, Chui, Stephen Y., Clark, Amy S., Clennell, Julia L., Datnow, Brian, DeMichele, Angela M., Duan, Xiuzhen, Edmiston, Kirsten K., Elias, Anthony D., Ellis, Erin D., Esserman, Laura L., Euhus, David M., Fadare, Oluwole, Fan, Fang, Feldman, Michael D, Forero-Torres, Andres, Haley, Barbara B., Han, Hyo S., Harada, Shuko, Haugen, Patricia, Helsten, Teresa, Hirst, Gillian L., Hylton, Nola M., Isaacs, Claudine, Kemmer, Kathleen, Khan, Qamar J., Khazai, Laila, Klein, Molly E., Krings, Gregor, Lang, Julie E., LeBeau, Lauren G., Leyland-Jones, Brian, Liu, Minetta C., Lo, Shelly, Lu, Janice, Magliocco, Anthony, Matthews, Jeffrey B., Melisko, Michelle E., Mhawech-Fauceglia, Paulette, Moulder, Stacy L., Murthy, Rashmi K., Nanda, Rita, Northfelt, Donald W., Ocal, Idris T., Olopade, Olufunmilayo, Pambuccian, Stefan, Paoloni, Melissa, Park, John W., Parker, Barbara A., Perlmutter, Jane, Peterson, Garry, Pusztai, Lajos, Rendi, Mara, Rugo, Hope S., Sahoo, Sunati, Sams, Sharon, Sanil, Ashish, Sattar, Husain, Schwab, Richard B., Singhrao, Ruby, Steeg, Katherine, Stringer-Reasor, Erica, Symmans, W. Fraser, Tawfik, Ossama, Tripathy, Debasish, Troxell, Megan L., van't Veer, Laura J., Venters, Sara J., Vinh, Tuyethoa, Viscusi, Rebecca K., Wallace, Anne M., Wei, Shi, Wilson, Amy, Yau, Christina, Yee, Douglas, Zeck, Jay C., Osdoit, Marie, van der Noordaa, Marieke, Shad, Sonal, Wei, Jane, de Croze, Diane, Hamy, Anne-Sophie, Laé, Marick, Reyal, Fabien, Sonke, Gabe S, Steenbruggen, Tessa G, van Seijen, Maartje, Wesseling, Jelle, Martín, Miguel, del Monte-Millán, Maria, López-Tarruella, Sara, Boughey, Judy C, Goetz, Matthew P, Hoskin, Tanya, Gould, Rebekah, Valero, Vicente, Edge, Stephen B, Abraham, Jean E, Bartlett, John M S, Caldas, Carlos, Dunn, Janet, Earl, Helena, Hayward, Larry, Hiller, Louise, Provenzano, Elena, Sammut, Stephen-John, Thomas, Jeremy S, Cameron, David, Graham, Ashley, Hall, Peter, Mackintosh, Lorna, Godwin, Andrew K, Schwensen, Kelsey, Sharma, Priyanka, DeMichele, Angela M, Cole, Kimberly, Kim, Mi-Ok, van 't Veer, Laura J, Esserman, Laura J, and Symmans, W Fraser

Published
2022
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10. Multi-omic machine learning predictor of breast cancer therapy response

Author

Sammut, Stephen-John, Crispin-Ortuzar, Mireia, Chin, Suet-Feung, Provenzano, Elena, Bardwell, Helen A., Ma, Wenxin, Cope, Wei, Dariush, Ali, Dawson, Sarah-Jane, Abraham, Jean E., Dunn, Janet, Hiller, Louise, Thomas, Jeremy, Cameron, David A., Bartlett, John M. S., Hayward, Larry, Pharoah, Paul D., Markowetz, Florian, Rueda, Oscar M., Earl, Helena M., and Caldas, Carlos

Published
2022
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11. Evaluating the effectiveness of abbreviated breast MRI (abMRI) interpretation training for mammogram readers: a multi-centre study assessing diagnostic performance, using an enriched dataset

Author

Jones, Lyn I., Marshall, Andrea, Elangovan, Premkumar, Geach, Rebecca, McKeown-Keegan, Sadie, Vinnicombe, Sarah, Harding, Sam A., Taylor-Phillips, Sian, Halling-Brown, Mark, Foy, Christopher, O’Flynn, Elizabeth, Ghiasvand, Hesam, Hulme, Claire, and Dunn, Janet A.

Published
2022
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13. Volatile vs Total intravenous Anaesthesia for major non-cardiac surgery: A pragmatic randomised triaL (VITAL)

Author

Yeung, Joyce, primary, Jhanji, Shaman, additional, Braun, John, additional, Dunn, Janet, additional, Eggleston, Lucy, additional, Frempong, Samuel, additional, Hiller, Louise, additional, Jacques, Claire, additional, Jefford, Monica, additional, Mason, James, additional, Moonesinghe, Ramani, additional, Pearse, Rupert, additional, Shelley, Benjamin, additional, and Vindrola, Cecilia, additional

Published
2024
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15. Treatment of cancer‐associated venous thromboembolism: 12‐month outcomes of the placebo versus rivaroxaban randomization of the SELECT‐D Trial (SELECT‐D: 12m)

Author

Marshall, Andrea, Levine, Mark, Hill, Catherine, Hale, Danielle, Thirlwall, Jenny, Wilkie, Veronica, French, Karen, Kakkar, Ajay, Lokare, Anand, Maraveyas, Anthony, Chapman, Oliver, Arif, Azra, Petrou, Stavros, Maredza, Mandy, Hobbs, Richard, Dunn, Janet A., and Young, Annie M.

Published
2020
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16. Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study

Author

Azam, Ayesha S, primary, Tsang, Yee‐Wah, additional, Thirlwall, Jenny, additional, Kimani, Peter K, additional, Sah, Shatrughan, additional, Gopalakrishnan, Kishore, additional, Boyd, Clinton, additional, Loughrey, Maurice B, additional, Kelly, Paul J, additional, Boyle, David P, additional, Salto‐Tellez, Manuel, additional, Clark, David, additional, Ellis, Ian O, additional, Ilyas, Mohammad, additional, Rakha, Emad, additional, Bickers, Adam, additional, Roberts, Ian S D, additional, Soares, Maria F, additional, Neil, Desley A H, additional, Takyi, Abi, additional, Raveendran, Sinthuri, additional, Hero, Emily, additional, Evans, Harriet, additional, Osman, Rania, additional, Fatima, Khunsha, additional, Hughes, Rhian W, additional, McIntosh, Stuart A, additional, Moran, Gordon W, additional, Ortiz‐Fernandez‐Sordo, Jacobo, additional, Rajpoot, Nasir M, additional, Storey, Ben, additional, Ahmed, Imtiaz, additional, Dunn, Janet A, additional, Hiller, Louise, additional, and Snead, David R J, additional

Published
2024
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18. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author

Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian’an, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, consortium, The CVD50, Cupples, L Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, Hoed, Marcel den, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E, Jukema, J Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Markus, Peters, Annette, Poole, Christopher J, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, and Trompet, Stella

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Diabetes, Human Genome, Cardiovascular, Prevention, Obesity, Genetics, Heart Disease, Heart Disease - Coronary Heart Disease, Clinical Trials and Supportive Activities, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Alleles, Coronary Disease, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Genotype, Glucagon-Like Peptide-1 Receptor, Humans, Receptor, Cannabinoid, CB2, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Sodium-Glucose Transporter 1, CVD50 consortium, GERAD_EC Consortium, Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology, Alzheimer’s Disease Genetics Consortium, Pancreatic Cancer Cohort Consortium, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease, EPIC-InterAct, CHARGE consortium, CHD Exome+ Consortium, CARDIOGRAM Exome Consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Published
2016

19. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial

Author

Drayson, Mark T, Bowcock, Stella, Planche, Tim, Iqbal, Gulnaz, Pratt, Guy, Yong, Kwee, Wood, Jill, Raynes, Kerry, Higgins, Helen, Dawkins, Bryony, Meads, David, Hulme, Claire T, Monahan, Irene, Karunanithi, Kamaraj, Dignum, Helen, Belsham, Edward, Neilson, Jeff, Harrison, Beth, Lokare, Anand, Campbell, Gavin, Hamblin, Michael, Hawkey, Peter, Whittaker, Anna C, Low, Eric, and Dunn, Janet A

Published
2019
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20. The QuinteT Recruitment Intervention supported five randomized trials to recruit to target: a mixed-methods evaluation

Author

Rogers, Chris A., Andrews, Robert, Blazeby, Jane M., Byrne, James, Donovan, Jenny L., Kelly, Jamie, Mazza, Graziella, Mahon, David, Noble, Hamish, Reeves, Barnaby C., Thompson, Janice L., Wordsworth, Sarah, Welbourn, Richard, Beard, David, Carr, Andrew, Cook, Jonathan, Cooper, Cushla, Dean, Benjamin, Gray, Alastair, Gwilym, Stephen, Judge, Andrew, Merritt, Naomi, Moser, Jane, Rees, Jonathan, Rombach, Ines, Savulescu, Julian, Tracey, Irene, Wartolowska, Karolina, Harrison, Eleanor, Tan, Wei, Mills, Nicola, Karantana, Alexia, Sprange, Kirsty, Duley, Lelia, Elliott, Daisy, Hollingworth, William, Montgomery, Alan A., Davis, Tim, Stein, Rob, Bartlett, John, Cameron, David, Campbell, Amy, Canney, Peter, Dunn, Janet, Earl, Helena, Falzon, Mary, Francis, Adele, Hall, Peter, Harmer, Victoria, Higgins, Helen, Hiller, Louise, Hughes-Davies, Luke, Hulme, Claire, Macpherson, Iain, Makris, Andreas, Marshall, Andrea, McCabe, Christopher, Morgan, Adrienne, Pinder, Sarah, Poole, Christopher, Provenzano, Elena, Rea, Daniel, Stallard, Nigel, Avery, Kerry N.L., Barham, C. Paul, Berrisford, Richard, Elliott, Jackie, Falk, Stephen J., Goldin, Rob, Hanna, George, Hollowood, Andrew A., Krysztopik, Richard, Metcalfe, Chris, Noble, Sian, Sanders, Grant, Streets, Christopher G., Titcomb, Dan R., Wheatley, Tim, Rooshenas, Leila, Scott, Lauren J., Tilling, Kate M., Husbands, Samantha, Conefrey, Carmel, Stein, Robert C., Carr, Andrew J., Beard, David J., Paramasivan, Sangeetha, Jepson, Marcus, Avery, Kerry, and Wilson, Caroline

Published
2019
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21. Mammographic surveillance after breast cancer.

Author

Evans, Andy, Dunn, Janet, and Donnelly, Peter Kevin

Subjects
*BREAST, *TRIPLE-negative breast cancer, *BREAST cancer, *BREAST implants, *SCREEN time
Abstract

Early detection of local recurrence has been shown to improve survival. What is unclear is how frequently mammography should be performed, how long surveillance should continue and how the answers to these questions vary with tumour pathology, patients age, and surgery type. Many of these questions are not directly answerable from the current literature. While some of these questions will be answered by the Mammo-50 study, evidence from local recurrence rates, tumour biology, and the lead time of mammography can be used to guide policy. Young age is the strongest predictor of local recurrence and given the short lead time of screening in women under 50, these women require annual mammography. Women over 50 with HER-2 positive and triple negative breast cancer have higher rates of local recurrence after breast conserving surgery than women with luminal cancers. Women with HER-2 positive and triple negative breast cancer also have a higher rate of recurrence in years 1-3 post surgery. Annual mammography in year 1-4 would appear justified. Women over 50 with luminal cancers have low rates of local recurrence and no early peak. Recurrence growth will be low due to tumour biology and hormone therapy. Biennial mammography after year 2 would seem appropriate. Women over 50 following mastectomy have no early peak in contralateral cancers so the frequency should be determined by the lead time of screening. This would suggest 2 yearly mammography for women aged 50-60 while 3 yearly mammography may suffice for women over 60. [ABSTRACT FROM AUTHOR]

Published
2024
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24. An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment

Author

Beard, David, Carr, Andrew, Cook, Jonathan, Cooper, Cushla, Dean, Benjamin, Donovan, Jenny L., Gray, Alastair, Gwilym, Stephen, Judge, Andrew, Merritt, Naomi, Moser, Jane, Rees, Jonathan, Rombach, Ines, Savulescu, Julian, Tracey, Irene, Wartolowska, Karolina, Blazeby, Jane M., Barham, Paul, Brookes, Sara T., Crosby, Tom, Falk, Stephen J., Griffin, S. Michael, Hollingworth, William, Hollowood, Andrew D., Krysztopik, Richard, Lewis, Wyn, Nicklin, Jo, Streets, Christopher, Strong, Sean, Titcomb, Dan, Williams, Geraint, Birtle, Alison, Bryan, Rik, Catto, James, Chester, John, French, Ann, Hall, Emma, Harris, Chris, Johnson, Mark, Jones, Rob, Keeley, Francis, Kirkbank, Tony, Kockelbergh, Roger, Lewis, Rebecca, Newton, Michelle, Powles, Thomas, Waters, Rachel, Winterbottom, Andrew, Halliday, Alison, Becquemin, Jean-Pierre, Belli, Anna, Bosiers, Marc, Cao, Piergiorgio, Davies, Christina, Gough, Michael, Hayter, Elizabeth, Leopold, Peter, McDonald, Sumaira, Michaels, Jonathan, Mihaylova, Borislava, Peto, Richard, Robertson, Steven, Rothwell, Peter, Scott, Rachael, Thomas, Dafydd, Vermassen, Frank, Stein, Rob, Bartlett, John, Cameron, David, Campbell, Amy, Canney, Peter, Dunn, Janet, Earl, Helena, Falzon, Mary, Francis, Adele, Hall, Peter, Harmer, Victoria, Higgins, Helen, Hiller, Louise, Hughes-Davies, Luke, Hulme, Claire, Macpherson, Iain, Makris, Andreas, Marshall, Andrea, McCabe, Christopher, Morgan, Adrienne, Pinder, Sarah, Poole, Christopher, Rea, Daniel, Stallard, Nigel, Jepson, Marcus, Elliott, Daisy, Conefrey, Carmel, Wade, Julia, Rooshenas, Leila, and Wilson, Caroline

Published
2018
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26. Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial

Author

Thomas, Jeremy St John, Provenzano, Elena, Hiller, Louise, Dunn, Janet, Blenkinsop, Clare, Grybowicz, Louise, Vallier, Anne-Laure, Gounaris, Ioannis, Abraham, Jean, Hughes-Davies, Luke, McAdam, Karen, Chan, Stephen, Ahmad, Rizvana, Hickish, Tamas, Houston, Stephen, Rea, Daniel, Caldas, Carlos, Bartlett, John MS, Cameron, David Allan, Hayward, Richard Laurence, and Earl, Helena Margaret

Published
2017
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27. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial

Author

Earl, Helena M, Hiller, Louise, Howard, Helen C, Dunn, Janet A, Young, Jennie, Bowden, Sarah J, McDermaid, Michelle, Waterhouse, Anna K, Wilson, Gregory, Agrawal, Rajiv, O'Reilly, Susan, Bowman, Angela, Ritchie, Diana M, Goodman, Andrew, Hickish, Tamas, McAdam, Karen, Cameron, David, Dodwell, David, Rea, Daniel W, Caldas, Carlos, Provenzano, Elena, Abraham, Jean E, Canney, Peter, Crown, John P, Kennedy, M John, Coleman, Robert, Leonard, Robert C, Carmichael, James A, Wardley, Andrew M, and Poole, Christopher J

Published
2017
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34. Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial

Author

Bowcock, Stella, primary, Atkin, Catherine, additional, Iqbal, Gulnaz, additional, Pratt, Guy, additional, Yong, Kwee, additional, Neal, Richard D., additional, Planche, Tim, additional, Karunanithi, Kamaraj, additional, Jenkins, Stephen, additional, Stern, Simon, additional, Arnott, Sarah, additional, Toth, Peter, additional, Wandroo, Farooq, additional, Dunn, Janet, additional, and Drayson, Mark T., additional

Published
2023
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37. Supplementary Tables 1 - 5, Figures 1 - 2 from Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel

Author

Abraham, Jean E., primary, Guo, Qi, primary, Dorling, Leila, primary, Tyrer, Jonathan, primary, Ingle, Susan, primary, Hardy, Richard, primary, Vallier, Anne-Laure, primary, Hiller, Louise, primary, Burns, Russell, primary, Jones, Linda, primary, Bowden, Sarah J., primary, Dunn, Janet A., primary, Poole, Christopher J., primary, Caldas, Carlos, primary, Pharoah, Paul P.D., primary, and Earl, Helena M., primary

Published
2023
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38. Abstract OT1-09-02: ATNEC: A multicentre, randomized trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the axillary lymph nodes after neoadjuvant chemotherapy

Author

Goyal, Amit, primary, Nicholls, Sophie, additional, Marshall, Andrea, additional, Hammonds, Natalie, additional, Wheatley, Duncan, additional, Elsberger, Beatrix, additional, Rose, Janice, additional, Edwards, Helen-Teresa, additional, Butt, Roeum, additional, Shaaban, Abeer, additional, Puri, Shama, additional, Ahmed, Samreen, additional, Homer, Tara, additional, Vale, Luke, additional, Bruce, Julie, additional, Gasson, Sophie J., additional, Higgins, Helen, additional, and Dunn, Janet A., additional

Published
2023
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40. Abstract OT3-32-01: OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer

Author

Stein, Robert, primary, Makris, Andreas, additional, Macpherson, Iain, additional, Hughes-Davies, Luke, additional, Marshall, Andrea, additional, Dotchin, Georgina, additional, Cameron, David A., additional, Kiely, Belinda E., additional, Wilson, Caroline, additional, Armstrong, Anne, additional, Earl, Helena M., additional, Poole, Christopher J., additional, Tsang, Janice, additional, Naume, Bjørn, additional, Rea, Daniel, additional, Ohnstad, Hege, additional, Hall, Peter S., additional, McIntosh, Stuart A., additional, Shinkins, Bethany, additional, McCabe, Christopher, additional, Morgan, Adrienne, additional, Bartlett, John MS, additional, and Dunn, Janet A., additional

Published
2023
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41. Digital Pathology for Reporting Histopathology Samples, Including Cancer Screening Samples – Definitive Evidence from a Multi-Site Study

Author

Azam, A. S., primary, Tsang, YW, additional, Thirlwall, J., additional, Kimani, Peter K., additional, Sah, S, additional, Gopalakrishnan, K, additional, Boyd, C, additional, Loughrey, MB, additional, Kelly, P. J., additional, Boyle, D. P., additional, Salto-Tellez, M, additional, Clark, D, additional, Ellis, IO, additional, Ilyas, M, additional, Rakha, E, additional, Bickers, A, additional, Roberts, Ian SD, additional, Soares, M. F., additional, Neil, Desley, additional, Takyi, A, additional, Raveendran, S, additional, Hero, E, additional, Evans, H, additional, Osman, R, additional, Fatima, K, additional, Hughes, RW, additional, Dunn, Janet, additional, Hiller, Bsc Louise, additional, and Snead, David Robert John, additional

Published
2023
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43. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial

Author

Earl, Helena M, Hiller, Louise, Dunn, Janet A, Blenkinsop, Clare, Grybowicz, Louise, Vallier, Anne-Laure, Abraham, Jean, Thomas, Jeremy, Provenzano, Elena, Hughes-Davies, Luke, Gounaris, Ioannis, McAdam, Karen, Chan, Stephen, Ahmad, Rizvana, Hickish, Tamas, Houston, Stephen, Rea, Daniel, Bartlett, John, Caldas, Carlos, Cameron, David A, and Hayward, Larry

Published
2015
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45. Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study

Author

Corrie, Pippa G, Marshall, Andrea, Dunn, Janet A, Middleton, Mark R, Nathan, Paul D, Gore, Martin, Davidson, Neville, Nicholson, Steve, Kelly, Charles G, Marples, Maria, Danson, Sarah J, Marshall, Ernest, Houston, Stephen J, Board, Ruth E, Waterston, Ashita M, Nobes, Jenny P, Harries, Mark, Kumar, Satish, Young, Gemma, and Lorigan, Paul

Published
2014
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46. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial

Author

Earl, Helena M, Vallier, Anne-Laure, Hiller, Louise, Fenwick, Nicola, Young, Jennie, Iddawela, Mahesh, Abraham, Jean, Hughes-Davies, Luke, Gounaris, Ioannis, McAdam, Karen, Houston, Stephen, Hickish, Tamas, Skene, Anthony, Chan, Stephen, Dean, Susan, Ritchie, Diana, Laing, Robert, Harries, Mark, Gallagher, Christopher, Wishart, Gordon, Dunn, Janet, Provenzano, Elena, and Caldas, Carlos

Published
2014
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47. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial

Author

Ford, Hugo E R, Marshall, Andrea, Bridgewater, John A, Janowitz, Tobias, Coxon, Fareeda Y, Wadsley, Jonathan, Mansoor, Wasat, Fyfe, David, Madhusudan, Srinivasan, Middleton, Gary W, Swinson, Daniel, Falk, Stephen, Chau, Ian, Cunningham, David, Kareclas, Paula, Cook, Natalie, Blazeby, Jane M, and Dunn, Janet A

Published
2014
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49. Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials

Author

Rischin, D., Mehanna, H., Young, R. J., Bressel, M., Dunn, Janet A., Corry, J., Soni, P., Fulton-Lieuw, T., Iqbal, G., Kenny, L., Porceddu, S., Wratten, C., Robinson, M., Solomon, B. J., HASH(0x5651c987e5b8), and HASH(0x5651c97cfdb0)

Subjects
RC0254, Oncology, Hematology
Abstract

Background\ud High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis.\ud \ud Patients and methods\ud We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (

Published
2022

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