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1. Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer—a prospective national multicentre study (EMIT-1)

Author

Ohnstad, H.O., Blix, E.S., Akslen, L.A., Gilje, B., Raj, S.X., Skjerven, H., Borgen, E., Janssen, E.A.M., Mortensen, E., Brekke, M.B., Falk, R.S., Schlichting, E., Boge, B., Songe-Møller, S., Olsson, P., Heie, A., Mannsåker, B., Vestlid, M.A., Kursetgjerde, T., Gravdehaug, B., Suhrke, P., Sanchez, E., Bublevic, J., Røe, O.D., Geitvik, G.A., Halset, E.H., Rypdal, M.C., Langerød, A., Lømo, J., Garred, Ø., Porojnicu, A., Engebraaten, O., Geisler, J., Lyngra, M., Hansen, M.H., Søiland, H., Nakken, T., Asphaug, L., Kristensen, V., Sørlie, T., Nygård, J.F., Kiserud, C.E., Reinertsen, K.V., Russnes, H.G., and Naume, B.

Published
2024
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8. 1694P Single cell characterization of longitudinal biopsies from breast cancer patients treated with the aromatase inhibitor letrozole and the CDK4/6 inhibitor ribociclib

Author

Tekpli, X., primary, Ghannoum, S., additional, Steen, C.B., additional, Fongård, M., additional, Holm, B.C., additional, Bosnjak, T., additional, Reitsma, L.C., additional, Geisler, S.B., additional, Seyedzadeh, M., additional, Buvarp, U-C., additional, Loeng, M., additional, Lyngra, M., additional, Kristensen, V., additional, and Geisler, J., additional

Published
2022
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11. DNA copy number motifs are strong and independent predictors of survival in breast cancer

Author

Pladsen, A.V., Nilsen, G., Rueda, O.M., Aure, M.R., Borgan, Ø., Liestøl, K., Vitelli, V., Frigessi, A., Langerød, A., Mathelier, A., Bathen, T.F., Borgen, E., Børresen-Dale, A.-L., Engebråten, O., Fritzman, B., Garred, Ø., Geisler, J., Geitvik, G.A., Hofvind, S., Kristensen, V., Kåresen, R., Lingjærde, O.C., Mælandsmo, G.M., Naume, B., Russnes, H.G., Sahlberg, K.K., Sauer, T., Skjerven, H.K., Schlichting, E., Sørlie, T., Wedge, D.C., Van Loo, P., Caldas, C., Pladsen, Arne V [0000-0001-7765-6823], Rueda, Oscar M [0000-0003-0008-4884], Mathelier, Anthony [0000-0001-5127-5459], Wedge, David C [0000-0002-7572-3196], Van Loo, Peter [0000-0003-0292-1949], Caldas, Carlos [0000-0003-3547-1489], Russnes, Hege G [0000-0001-8724-1891], Lingjærde, Ole Christian [0000-0003-3565-4912], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Genome instability, Gene Dosage, Medicine (miscellaneous), Tumour biomarkers, chemistry.chemical_compound, Breast cancer, 0302 clinical medicine, Risk Factors, Databases, Genetic, Cancer genomics, Computational models, lcsh:QH301-705.5, Manchester Cancer Research Centre, food and beverages, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Female, General Agricultural and Biological Sciences, Algorithms, DNA Copy Number Variations, Clinical Decision-Making, Breast Neoplasms, Computational biology, Biology, Risk Assessment, Article, General Biochemistry, Genetics and Molecular Biology, Genomic Instability, 03 medical and health sciences, Predictive Value of Tests, medicine, Biomarkers, Tumor, Humans, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Gene Expression Profiling, fungi, Cancer, medicine.disease, 030104 developmental biology, chemistry, lcsh:Biology (General), Spatial behavior, Personalized medicine, business, Outcome prediction, Transcriptome, Genome architecture, DNA
Abstract

Somatic copy number alterations are a frequent sign of genome instability in cancer. A precise characterization of the genome architecture would reveal underlying instability mechanisms and provide an instrument for outcome prediction and treatment guidance. Here we show that the local spatial behavior of copy number profiles conveys important information about this architecture. Six filters were defined to characterize regional traits in copy number profiles, and the resulting Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to tumors in four breast cancer cohorts (n = 2919). The derived motifs represent a layer of information that complements established molecular classifications of breast cancer. A score reflecting presence or absence of motifs provided a highly significant independent prognostic predictor. Results were consistent between cohorts. The nonsite-specific occurrence of the detected patterns suggests that CARMA captures underlying replication and repair defects and could have a future potential in treatment stratification., Pladsen et al. develop Copy Aberration Regional Mapping Analysis (CARMA), an algorithm that derives motifs for copy number profiles in breast cancers by integrating several features, to predict breast cancer prognosis and stratifications. Their algorithm can detect replication and repair defects and can be used in personalized medicine.

Published
2020
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12. Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes

Author

Mavaddat, N, Dorling, L, Carvalho, S, Allen, J, Gonzalez-Neira, A, Keeman, R, Bolla, MK, Dennis, J, Wang, Q, Ahearn, TU, Andrulis, IL, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Briceno, I, Bruning, T, Camp, NJ, Campbell, A, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Christiansen, H, Czene, K, Dork, T, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Geisler, J, Giles, GG, Guenel, P, Hadjisavvas, A, Hahnen, E, Hall, P, Hamann, U, Hartikainen, JM, Hartman, M, Hoppe, R, Howell, A, Jakubowska, A, Jung, A, Khusnutdinova, EK, Kristensen, VN, Li, J, Lim, SH, Lindblom, A, Loizidou, MA, Lophatananon, A, Lubinski, J, Madsen, MJ, Mannermaa, A, Manoochehri, M, Margolin, S, Mavroudis, D, Milne, RL, Taib, NAM, Morra, A, Muir, K, Obi, N, Osorio, A, Park-Simon, T-W, Peterlongo, P, Radice, P, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Shah, M, Sim, X, Southey, MC, Thorne, H, Tomlinson, I, Torres, D, Truong, T, Yip, CH, Spurdle, AB, Vreeswijk, MPG, Dunning, AM, Garcia-Closas, M, Pharoah, PDP, Kvist, A, Muranen, TA, Nevanlinna, H, Teo, SH, Devilee, P, Schmidt, MK, Easton, DF, Mavaddat, N, Dorling, L, Carvalho, S, Allen, J, Gonzalez-Neira, A, Keeman, R, Bolla, MK, Dennis, J, Wang, Q, Ahearn, TU, Andrulis, IL, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Briceno, I, Bruning, T, Camp, NJ, Campbell, A, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Christiansen, H, Czene, K, Dork, T, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Geisler, J, Giles, GG, Guenel, P, Hadjisavvas, A, Hahnen, E, Hall, P, Hamann, U, Hartikainen, JM, Hartman, M, Hoppe, R, Howell, A, Jakubowska, A, Jung, A, Khusnutdinova, EK, Kristensen, VN, Li, J, Lim, SH, Lindblom, A, Loizidou, MA, Lophatananon, A, Lubinski, J, Madsen, MJ, Mannermaa, A, Manoochehri, M, Margolin, S, Mavroudis, D, Milne, RL, Taib, NAM, Morra, A, Muir, K, Obi, N, Osorio, A, Park-Simon, T-W, Peterlongo, P, Radice, P, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Shah, M, Sim, X, Southey, MC, Thorne, H, Tomlinson, I, Torres, D, Truong, T, Yip, CH, Spurdle, AB, Vreeswijk, MPG, Dunning, AM, Garcia-Closas, M, Pharoah, PDP, Kvist, A, Muranen, TA, Nevanlinna, H, Teo, SH, Devilee, P, Schmidt, MK, and Easton, DF

Abstract

IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021. EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2- high-grade subt

Published
2022

13. Current treatment landscape of HR+/HER2-advanced breast cancer in the Nordics : A modified Delphi study

Author

Karihtala, P., Valachis, A, Tuxen, M., Geisler, J., Karihtala, P., Valachis, A, Tuxen, M., and Geisler, J.

Abstract

Background: The aim of this Delphi study was to assess current perspectives on HR+/HER2- advanced breast cancer (aBC) treatment strategies among Nordic BC oncologists, and to gain broader understanding of the uptake and implementation of novel treatments. Methods: A modified, three round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection and questionnaires development. The questionnaires covered clinically relevant topics related to HR+/HER2- aBC treatment: treatment patterns in different lines of therapy (first- (1L), second- (2L) and third-line (3L)), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. Results: In total 28 panelists participated in the study. In rounds one and two, 14 and 21 questions reached consensuses, respectively. Thirteen non-consensus reaching questions were reposted in round three, where 10 reached consensus. Overall, topics that reached a high consensus level included: treatment approaches in 1L and 2L treatment setting for HR+/HER2- aBC, treatment of oligometastatic disease, visceral crisis and brain metastases, and age-related treatment considerations. No consensus was reached for aspects regarding 3L therapy and de novo aBC. Endocrine therapy (ET) combined with CDK4/6i was the treatment of choice for both 1L and 2L therapy. Regarding implementation of clinical guidelines, a discrepancy was observed between treatments recommended in guidelines and those used in clinical practice, especially in cases where novel treatments were proposed. Conclusions: Endocrine therapy combined with a CDK4/6i is the frontline treatment choice for HR+/HER2- aBC in the Nordics. Observed discrepancies between international clinical guidelines and practice are partly due to difference in the availability of

Published
2022
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18. Word Choice and Collocates of Doka and Martin’s Grieving Styles

Author

Geisler J and Dykeman C

Subjects
Word choice, Psychology, Linguistics
Abstract

It has been over two decades since the concepts of instrumental and intuitive grief have entered the field of grief and loss. In this time, there has not been a study that attempts to understand the language used among these two grief styles until now. In this study, a corpus linguistic program called #Lancsbox was used to analyze the collocates of the top words found in each grief style. Results of this study show that the word “death” is exclusive to the top words of instrumental grief over its counterpart. Contrary to what one would expect from the cognitively-oriented instrumental griever, node words such as “like” offered collocates of emotions, while words high in intensity were collocates among the intuitive grief vignettes. This study contributes to the field of grief work and includes several implications for both counseling and research, both of which are provided to the reader. Keywords: graphcoll, collocation, grief, Doka, Martin, corpus linguistics

Published
2021
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20. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author

Park, HA, Neumeyer, S, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baten, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Børresen-Dale, A-L, Grenaker Alnæs, GI, Sahlberg, KK, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, CE, Reinertsen, KV, Helland, Å, Riis, M, Geisler, J, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Grip, M, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Han, S, Harkness, EF, Hart, SN, He, W, Heemskerk-Gerritsen, BAM, Hopper, JL, Hunter, DJ, Clarke, C, Marsh, D, Scott, R, Baxter, R, Yip, D, Carpenter, J, Davis, A, Pathmanathan, N, Simpson, P, Graham, D, Sachchithananthan, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Bennett, I, Bogwitz, M, Botes, L, Brennan, M, Brown, M, Buckley, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Chauhan, D, Chauhan, M, Christian, A, Cohen, P, Colley, A, Crook, A, Cui, J, Cummings, M, Dawson, S-J, DeFazio, A, Delatycki, M, Dickson, R, Dixon, J, Edkins, T, Edwards, S, Farshid, G, Fellows, A, Fenton, G, Field, M, Flanagan, J, Fong, P, Forrest, L, Fox, S, French, J, Friedlander, M, Gaff, C, Gattas, M, George, P, Greening, S, Harris, M, Hart, S, Hayward, N, Hopper, J, Hoskins, C, Hunt, C, James, P, Jenkins, M, Kidd, A, Kirk, J, Koehler, J, Kollias, J, Lakhani, S, Lawrence, M, Lindeman, G, Lipton, L, Lobb, L, Mann, G, McLachlan, SA, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, O’Sullivan, S, Ortega, DG, Pachter, N, Patterson, B, Pearn, A, Phillips, K, Pieper, E, Rickard, E, Robinson, B, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Sexton, A, Shelling, A, Southey, M, Spurdle, A, Taylor, J, Taylor, R, Thorne, H, Trainer, A, Tucker, K, Visvader, J, Walker, L, Williams, R, Winship, I, Young, MA, Jager, A, Jakubowska, A, John, EM, Jung, A, Kaaks, R, Kapoor, PM, Keeman, R, Khusnutdinova, E, Kitahara, CM, Koppert, LB, Koutros, S, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lo, W-Y, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Muranen, TA, Nevanlinna, H, Newman, WG, Nordestgaard, BG, Offit, K, Olshan, AF, Olsson, H, Park-Simon, T-W, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Radice, P, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schwentner, L, Shah, M, Shu, X-O, Simard, J, Smeets, A, Southey, MC, Spinelli, JJ, Stevens, V, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Vijai, J, Wang, S, Wendt, C, Winqvist, R, Wolk, A, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Zheng, W, Kraft, P, Chang-Claude, J, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Park, Hanla A. [0000-0001-8055-3729], Dennis, Joe [0000-0003-4591-1214], Augustinsson, Annelie [0000-0003-3415-0536], Brenner, Hermann [0000-0002-6129-1572], Canzian, Federico [0000-0002-4261-4583], Cox, Angela [0000-0002-5138-1099], Devilee, Peter [0000-0002-8023-2009], Fasching, Peter A. [0000-0003-4885-8471], Harkness, Elaine F. [0000-0001-6625-7739], Hart, Steven N. [0000-0001-7714-2734], Heemskerk-Gerritsen, Bernadette A. M. [0000-0002-9724-6693], Jakubowska, Anna [0000-0002-5650-0501], Kapoor, Pooja Middha [0000-0001-5503-8215], Kurian, Allison W. [0000-0002-6175-9470], Newman, William G. [0000-0002-6382-4678], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Sawyer, Elinor J. [0000-0001-8285-4111], Scott, Christopher [0000-0003-1340-0647], Smeets, Ann [0000-0002-5091-6602], Tomlinson, Ian [0000-0003-3037-1470], Truong, Thérèse [0000-0002-2943-6786], Pharoah, Paul D. P. [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, Medicin och hälsovetenskap, Cancer Research, Genotyping Techniques, Breast Neoplasms, Case-Control Studies, Cigarette Smoking, Female, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, ALCOHOL, Medical and Health Sciences, 0302 clinical medicine, Breast cancer, Pleiotropy, Epidemiology, Medicine, TOBACCO, Breast Neoplasms/epidemiology, Cigarette Smoking/adverse effects, WOMEN, ASSOCIATION, Single Nucleotide, 3. Good health, Substance abuse, 692/699/67/1347, 030220 oncology & carcinogenesis, Life Sciences & Biomedicine, 692/499, medicine.medical_specialty, 3122 Cancers, Single-nucleotide polymorphism, Article, 03 medical and health sciences, Internal medicine, ddc:610, Polymorphism, Genetic association, Science & Technology, business.industry, Cancer, medicine.disease, 030104 developmental biology, Clinical research, Risk factors, TISSUE, INFERENCE, CIGARETTE-SMOKING, business
Abstract

Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

Published
2021
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21. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, TU, Zhang, H, Michailidou, K, Milne, RL, Bolla, MK, Dennis, J, Dunning, AM, Lush, M, Wang, Q, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baten, A, Becher, H, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bojesen, SE, Bonanni, B, Børresen-Dale, A-L, Brauch, H, Brenner, H, Brooks-Wilson, A, Brüning, T, Burwinkel, B, Buys, SS, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Sahlberg, KK, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, CE, Reinertsen, KV, Helland, Å, Riis, M, Geisler, J, Collée, JM, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Gago-Dominguez, M, Gapstur, SM, García-Sáenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, González-Neira, A, Alnæs, GIG, Grip, M, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, C, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Fox, S, Campbell, I, Bowtell, D, Spurdle, A, Webb, P, de Fazio, A, Tassell, M, Kirk, J, Lindeman, G, Price, M, Southey, M, Milne, R, Deb, S, Jakimovska, M, Jakubowska, A, John, EM, Jones, ME, Jung, A, Kaaks, R, Kauppila, S, Keeman, R, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Koutros, S, Kristensen, VN, Krüger, U, Kubelka-Sabit, K, Kurian, AW, Kyriacou, K, Lambrechts, D, Lee, DG, Lindblom, A, Linet, M, Lissowska, J, Llaneza, A, Lo, W-Y, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, McLean, C, Meindl, A, Menon, U, Nevanlinna, H, Newman, WG, Nodora, J, Offit, K, Olsson, H, Orr, N, Park-Simon, T-W, Patel, AV, Peto, J, Pita, G, Plaseska-Karanfilska, D, Prentice, R, Punie, K, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Rüdiger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Schöttker, B, Sherman, ME, Shu, X-O, Smichkoska, S, Southey, MC, Spinelli, JJ, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Teras, LR, Terry, MB, Torres, D, Troester, MA, Vachon, CM, van Deurzen, CHM, van Veen, EM, Wagner, P, Weinberg, CR, Wendt, C, Wesseling, J, Winqvist, R, Wolk, A, Yang, XR, Zheng, W, Couch, FJ, Simard, J, Kraft, P, Easton, DF, Pharoah, PDP, Schmidt, MK, García-Closas, M, Chatterjee, N, Ahearn, Thomas U [0000-0003-0771-7752], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Apollo - University of Cambridge Repository, Medicum, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, Clinical Genetics, Medical Oncology, and Pathology

Subjects
False discovery rate, Oncology, Common breast cancer susceptibility variants, Receptor, ErbB-2, Estrogen receptor, PROGRESSION, Etiologic heterogeneity, Logistic regression, Basic medicine, Breast cancer, 0302 clinical medicine, PRIMARY THERAPY, HETEROGENEITY, RC254-282, HISTOLOGICAL GRADE, 0303 health sciences, Breast Neoplasms/epidemiology, Receptors, Estrogen/genetics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, INTERNATIONAL EXPERT CONSENSUS, humanities, Receptor, ErbB-2/genetics, 3. Good health, Receptors, Estrogen, Receptors, Progesterone/genetics, 030220 oncology & carcinogenesis, Female, Biomarkers, Tumor/genetics, Receptors, Progesterone, Medical Genetics, Research Article, Risk, medicine.medical_specialty, SUSCEPTIBILITY LOCI, 3122 Cancers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, Biomarkers, Tumor, medicine, Genetic predisposition, Humans, ddc:610, GENOME-WIDE ASSOCIATION, Genetic association, Medicinsk genetik, 030304 developmental biology, Cancer och onkologi, medicine.disease, Cancer and Oncology, Clinical medicine, Genome-Wide Association Study
Abstract

Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate p Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

Published
2020
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22. Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

Author

Park H.A., Neumeyer S., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baten A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Brucker S.Y., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Clarke C.L., Borresen-Dale A.-L., Grenaker Alnaes G.I., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Grip M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S., Harkness E.F., Hart S.N., He W., Heemskerk-Gerritsen B.A.M., Hopper J.L., Hunter D.J., Clarke C., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Chenevix-Trench G., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Scott R., Sexton A., Shelling A., Simpson P., Southey M., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Jung A., Kaaks R., Kapoor P.M., Keeman R., Khusnutdinova E., Kitahara C.M., Koppert L.B., Koutros S., Kristensen V.N., Kurian A.W., Lacey J., Lambrechts D., Le Marchand L., Lo W.-Y., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Martinez M.E., Mavroudis D., Meindl A., Menon U., Milne R.L., Muranen T.A., Nevanlinna H., Newman W.G., Nordestgaard B.G., Offit K., Olshan A.F., Olsson H., Park-Simon T.-W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert H.S., Romero A., Saloustros E., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schoemaker M.J., Schwentner L., Scott C., Shah M., Shu X.-O., Simard J., Smeets A., Southey M.C., Spinelli J.J., Stevens V., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Zheng W., Kraft P., Chang-Claude J., Park H.A., Neumeyer S., Michailidou K., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baten A., Beane Freeman L.E., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Brucker S.Y., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Clarke C.L., Borresen-Dale A.-L., Grenaker Alnaes G.I., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fritschi L., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Grip M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Han S., Harkness E.F., Hart S.N., He W., Heemskerk-Gerritsen B.A.M., Hopper J.L., Hunter D.J., Clarke C., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Chenevix-Trench G., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Scott R., Sexton A., Shelling A., Simpson P., Southey M., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Jung A., Kaaks R., Kapoor P.M., Keeman R., Khusnutdinova E., Kitahara C.M., Koppert L.B., Koutros S., Kristensen V.N., Kurian A.W., Lacey J., Lambrechts D., Le Marchand L., Lo W.-Y., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Martinez M.E., Mavroudis D., Meindl A., Menon U., Milne R.L., Muranen T.A., Nevanlinna H., Newman W.G., Nordestgaard B.G., Offit K., Olshan A.F., Olsson H., Park-Simon T.-W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert H.S., Romero A., Saloustros E., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Schoemaker M.J., Schwentner L., Scott C., Shah M., Shu X.-O., Simard J., Smeets A., Southey M.C., Spinelli J.J., Stevens V., Swerdlow A.J., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Zheng W., Kraft P., and Chang-Claude J.

Abstract

Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Method(s): We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Result(s): Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 x 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion(s): Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.Copyright © 2021, The Author(s).

Published
2021

23. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Author

Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., Fletcher O., Johnson N., Maguire S., Morra A., Kapoor P.M., Tomczyk K., Jones M.E., Schoemaker M.J., Gilham C., Bolla M.K., Wang Q., Dennis J., Ahearn T.U., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arndt V., Aronson K.J., Augustinsson A., Baynes C., Freeman L.E.B., Beckmann M.W., Benitez J., Bermisheva M., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Brauch H., Brenner H., Burwinkel B., Campa D., Canzian F., Castelao J.E., Chanock S.J., Chenevix-Trench G., Clarke C.L., Borresen-Dale A.-L., Alnaes G.I.G., Sahlberg K.K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C.E., Reinertsen K.V., Helland A., Riis M., Geisler J., Conroy D.M., Couch F.J., Cox A., Cross S.S., Czene K., Dork T., Eliassen A.H., Engel C., Evans D.G., Fasching P.A., Figueroa J., Floris G., Flyger H., Gago-Dominguez M., Gapstur S.M., Garcia-Closas M., Gaudet M.M., Giles G.G., Goldberg M.S., Gonzalez-Neira A., Bowtell D.D.L., Webb P.M., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., Hooning M.J., Hopper J.L., Howell A., Hunter D.J., Clarke C., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Milne R.L., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Simpson P., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Jager A., Jakubowska A., John E.M., Keeman R., Khusnutdinova E., Kitahara C.M., Kosma V.-M., Koutros S., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Linet M., Lubinski J., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mavroudis D., Mayes R., Meindl A., Neuhausen S.L., Nevanlinna H., Newman W.G., Nielsen S.F., Nordestgaard B.G., Obi N., Olshan A.F., Olson J.E., Olsson H., Orban E., Park-Simon T.-W., Peterlongo P., Plaseska-Karanfilska D., Pylkas K., Rennert G., Rennert H.S., Ruddy K.J., Saloustros E., Sandler D.P., Sawyer E.J., Schmutzler R.K., Scott C., Shu X.-O., Simard J., Smichkoska S., Sohn C., Spinelli J.J., Stone J., Tamimi R.M., Taylor J.A., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Truong T., Vachon C.M., van Veen E.M., Wang S.S., Weinberg C.R., Wendt C., Wildiers H., Winqvist R., Wolk A., Zheng W., Ziogas A., Dunning A.M., Pharoah P.D.P., Easton D.F., Howie A.F., Peto J., dos-Santos-Silva I., Swerdlow A.J., Chang-Claude J., Schmidt M.K., Orr N., and Fletcher O.

Abstract

Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Method(s): We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Result(s): For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10-8). Conclusion(s): The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.Copyright © 2021, The Author(s).

Published
2021

24. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.

Author

Escala-Garcia M., Canisius S., Keeman R., Beesley J., Anton-Culver H., Arndt V., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Bermisheva M., Bojesen S.E., Bolla M.K., Brenner H., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Couch F.J., Czene K., Daly M.B., Dennis J., Devilee P., Dork T., Dunning A.M., Easton D.F., Ekici A.B., Eliassen A.H., Fasching P.A., Flyger H., Gago-Dominguez M., Garcia-Closas M., Garcia-Saenz J.A., Geisler J., Giles G.G., Grip M., Gundert M., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Hartikainen J.M., Heemskerk-Gerritsen B.A.M., Hollestelle A., Hoppe R., Hopper J.L., Hunter D.J., Jacot W., Jakubowska A., John E.M., Jung A.Y., Kaaks R., Khusnutdinova E., Koppert L.B., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Lindblom A., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Mavroudis D., Muranen T.A., Nevanlinna H., Olshan A.F., Olsson H., Park-Simon T.-W., Patel A.V., Peterlongo P., Pharoah P.D.P., Punie K., Radice P., Rennert G., Rennert H.S., Romero A., Roylance R., Rudiger T., Ruebner M., Saloustros E., Sawyer E.J., Schmutzler R.K., Schoemaker M.J., Scott C., Southey M.C., Surowy H., Swerdlow A.J., Tamimi R.M., Teras L.R., Thomas E., Tomlinson I., Troester M.A., Vachon C.M., Wang Q., Winqvist R., Wolk A., Ziogas A., Michailidou K., Chenevix-Trench G., Bachelot T., Schmidt M.K., Escala-Garcia M., Canisius S., Keeman R., Beesley J., Anton-Culver H., Arndt V., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Bermisheva M., Bojesen S.E., Bolla M.K., Brenner H., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Couch F.J., Czene K., Daly M.B., Dennis J., Devilee P., Dork T., Dunning A.M., Easton D.F., Ekici A.B., Eliassen A.H., Fasching P.A., Flyger H., Gago-Dominguez M., Garcia-Closas M., Garcia-Saenz J.A., Geisler J., Giles G.G., Grip M., Gundert M., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Hartikainen J.M., Heemskerk-Gerritsen B.A.M., Hollestelle A., Hoppe R., Hopper J.L., Hunter D.J., Jacot W., Jakubowska A., John E.M., Jung A.Y., Kaaks R., Khusnutdinova E., Koppert L.B., Kraft P., Kristensen V.N., Kurian A.W., Lambrechts D., Le Marchand L., Lindblom A., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Mavroudis D., Muranen T.A., Nevanlinna H., Olshan A.F., Olsson H., Park-Simon T.-W., Patel A.V., Peterlongo P., Pharoah P.D.P., Punie K., Radice P., Rennert G., Rennert H.S., Romero A., Roylance R., Rudiger T., Ruebner M., Saloustros E., Sawyer E.J., Schmutzler R.K., Schoemaker M.J., Scott C., Southey M.C., Surowy H., Swerdlow A.J., Tamimi R.M., Teras L.R., Thomas E., Tomlinson I., Troester M.A., Vachon C.M., Wang Q., Winqvist R., Wolk A., Ziogas A., Michailidou K., Chenevix-Trench G., Bachelot T., and Schmidt M.K.

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P=3.19x10-8 and 4.42x10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.Copyright © 2021. The Author(s).

Published
2021

25. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

Author

Escala-Garcia, M, Canisius, S, Keeman, R, Beesley, J, Anton-Culver, H, Arndt, V, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Bojesen, SE, Bolla, MK, Brenner, H, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Couch, FJ, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dork, T, Dunning, AM, Easton, DF, Ekici, AB, Eliassen, AH, Fasching, PA, Flyger, H, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Geisler, J, Giles, GG, Grip, M, Guendert, M, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hartikainen, JM, Heemskerk-Gerritsen, BAM, Hollestelle, A, Hoppe, R, Hopper, JL, Hunter, DJ, Jacot, W, Jakubowska, A, John, EM, Jung, AY, Kaaks, R, Khusnutdinova, E, Koppert, LB, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Lindblom, A, Luben, RN, Lubinski, J, Mannermaa, A, Manoochehri, M, Margolin, S, Mavroudis, D, Muranen, TA, Nevanlinna, H, Olshan, AF, Olsson, H, Park-Simon, T-W, Patel, AV, Peterlongo, P, Pharoah, PDP, Punie, K, Radice, P, Rennert, G, Rennert, HS, Romero, A, Roylance, R, Ruediger, T, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Scott, C, Southey, MC, Surowy, H, Swerdlow, AJ, Tamimi, RM, Teras, LR, Thomas, E, Tomlinson, I, Troester, MA, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Ziogas, A, Michailidou, K, Chenevix-Trench, G, Bachelot, T, Schmidt, MK, Escala-Garcia, M, Canisius, S, Keeman, R, Beesley, J, Anton-Culver, H, Arndt, V, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Bermisheva, M, Bojesen, SE, Bolla, MK, Brenner, H, Canzian, F, Castelao, JE, Chang-Claude, J, Chanock, SJ, Couch, FJ, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dork, T, Dunning, AM, Easton, DF, Ekici, AB, Eliassen, AH, Fasching, PA, Flyger, H, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Geisler, J, Giles, GG, Grip, M, Guendert, M, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hartikainen, JM, Heemskerk-Gerritsen, BAM, Hollestelle, A, Hoppe, R, Hopper, JL, Hunter, DJ, Jacot, W, Jakubowska, A, John, EM, Jung, AY, Kaaks, R, Khusnutdinova, E, Koppert, LB, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Lindblom, A, Luben, RN, Lubinski, J, Mannermaa, A, Manoochehri, M, Margolin, S, Mavroudis, D, Muranen, TA, Nevanlinna, H, Olshan, AF, Olsson, H, Park-Simon, T-W, Patel, AV, Peterlongo, P, Pharoah, PDP, Punie, K, Radice, P, Rennert, G, Rennert, HS, Romero, A, Roylance, R, Ruediger, T, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schoemaker, MJ, Scott, C, Southey, MC, Surowy, H, Swerdlow, AJ, Tamimi, RM, Teras, LR, Thomas, E, Tomlinson, I, Troester, MA, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Ziogas, A, Michailidou, K, Chenevix-Trench, G, Bachelot, T, and Schmidt, MK

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10-8 and 4.42 × 10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Published
2021

26. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

Author

Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), Schmidt, M. K. (Marjanka K.), Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), and Schmidt, M. K. (Marjanka K.)

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Published
2021

32. BRAF mutational status as a prognostic marker for survival in malignant melanoma:a systematic review and meta-analysis

Author

Ny, L. (L.), Hernberg, M. (M.), Nyakas, M. (M.), Koivunen, J. (J.), Oddershede, L. (L.), Yoon, M. (M.), Wang, X. (X.), Guyot, P. (P.), and Geisler, J. (J.)

Subjects
neoplasms
Abstract

Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies. Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09–1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I–III melanoma (combined HR: 1.16, 95% CI: 0.92–1.46), and on PFS in stage III–IV (HR: 0.98 (95% CI: 0.68−1.40)). Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.

Published
2020

33. Two truncating variants in FANCC and breast cancer risk

Author

Dork, T., Peterlongo, P., Mannermaa, A., Bolla, M.K., Wang, Q., Dennis, J., Ahearn, T., Andrulis, I.L., Anton-Culver, H., Arndt, V., Aronson, K.J., Augustinsson, A., Freeman, L.E.B., Beckmann, M.W., Beeghly-Fadiel, A., Behrens, S., Bermisheva, M., Blomqvist, C., Bogdanova, N., Bojesen, S.E., Brauch, H., Brenner, H., Burwinkel, B., Canzian, F., Chan, T.L., Chang-Claude, J., Chanock, S.J., Choi, J.Y., Christiansen, H., Clarke, C.L., Couch, F.J., Czene, K., Daly, M.B., dos-Santos-Silva, I., Dwek, M., Eccles, D.M., Ekici, A.B., Eriksson, M., Evans, D.G., Fasching, P.A., Figueroa, J., Flyger, H., Fritschisl, L., Gabrielson, M., Gago-Dominguez, M., Gao, C., Gapstur, S.M., Garcia-Closas, M., Garcia-Saenz, J.A., Gaudet, M.M., Giles, G.G., Goldberg, M.S., Goldgar, D.E., Guenel, P., Haeberle, L., Haiman, C.A., Hakansson, N., Hall, P., Hamann, U., Hartman, M., Hauke, J., Hein, A., Hillemanns, P., Hogervorst, F.B.L., Hooning, M.J., Hopper, J.L., Howell, T., Huo, D.Z., Ito, H., Iwasaki, M., Jakubowska, A., Janni, W., John, E.M., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Khusnutdinova, E., Kim, S.W., Kitahara, C.M., Koutros, S., Kraft, P., Kristensen, V.N., Kwon, A., Lambrechts, D., Marchand, L. le, Li, J.M., Lindstrom, S., Linet, M., W.Y. lo, Long, J.R., Lophatananon, A., Lubinski, J., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, E., Matsuo, K., Mavroudis, D., Meindl, A., Menon, U., Milne, R.L., Taib, N.A.M., Muir, K., Mulligan, A.M., Neuhausen, S.L., Nevanlinna, H., Neven, P., Newman, W.G., Offit, K., Olopade, O.I., Olshan, A.F., Olson, J.E., Olsson, H., Park, S.K., Park-Simon, T.W., Peto, J., Plaseska-Karanfilska, D., Pohl-Rescigno, E., Presneau, N., Rack, B., Radice, P., Rashid, M.U., Rennert, G., Rennert, H.S., Romero, A., Ruebner, M., Saloustros, E., Schmidt, M.K., Schmutzler, R.K., Schneider, M.O., Schoemaker, M.J., Scott, C., Shen, C.Y., Shu, X.O., Simard, J., Slager, S., Smichkoska, S., Southey, M.C., Spinelli, J.J., Stone, J., Surowy, H., Swerdlow, A.J., Tamimi, R.M., Tapper, W.J., Teo, S.H., Terry, M.B., Toland, A.E., Tollenaar, R.A.E.M., Torres, D., Torres-Mejia, G., Troester, M.A., Truong, T., Tsugane, S., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Veen, E.M. van, Vijai, J., Wendt, C., Wolk, A., Yu, J.C., Zheng, W., Ziogas, A., Ziv, E., Dunning, A.M., Pharoah, P.D.P., Schindler, D., Devilee, P., Easton, D.F., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C.S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Borresen-Dale, A.L., Alnaes, G.I.G., Sahlberg, K.K., Ottestad, L., Karesen, R., Schlichting, E., Holmen, M.M., Sauer, T., Haakensen, V., Engebraten, O., Naume, B., Fossa, A., Kiserud, C.E., Reinertsen, K.V., Helland, A., Riis, M., Geisler, J., ABCTB Investigators, NBCS Collaborators, Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Brauch, Hiltrud [0000-0001-7531-2736], Dwek, Miriam [0000-0001-7184-2932], Ekici, Arif B [0000-0001-6099-7066], Fasching, Peter A [0000-0003-4885-8471], Figueroa, Jonine [0000-0002-5100-623X], Hein, Alexander [0000-0003-2601-3398], Ito, Hidemi [0000-0002-8023-4581], Matsuo, Keitaro [0000-0003-1761-6314], Menon, Usha [0000-0003-3708-1732], Milne, Roger L [0000-0001-5764-7268], Muir, Kenneth [0000-0001-6429-988X], Nevanlinna, Heli [0000-0002-0916-2976], Newman, William G [0000-0002-6382-4678], Peto, Julian [0000-0002-1685-8912], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Schmidt, Marjanka K [0000-0002-2228-429X], Scott, Christopher [0000-0003-1340-0647], Stone, Jennifer [0000-0001-5077-0124], Truong, Thérèse [0000-0002-2943-6786], Tsugane, Shoichiro [0000-0003-4105-2774], Ziogas, Argyrios [0000-0003-4529-3727], Dunning, Alison M [0000-0001-6651-7166], Pharoah, Paul DP [0000-0001-8494-732X], Devilee, Peter [0000-0002-8023-2009], Easton, Douglas F [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Andrulis, Irene L. [0000-0002-4226-6435], Ekici, Arif B. [0000-0001-6099-7066], Fasching, Peter A. [0000-0003-4885-8471], Milne, Roger L. [0000-0001-5764-7268], Newman, William G. [0000-0002-6382-4678], Schmidt, Marjanka K. [0000-0002-2228-429X], Dunning, Alison M. [0000-0001-6651-7166], Pharoah, Paul D. P. [0000-0001-8494-732X], Easton, Douglas F. [0000-0003-2444-3247], HUS Comprehensive Cancer Center, Clinicum, University Management, Department of Oncology, University of Helsinki, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Medical Oncology, and Clinical Genetics

Subjects
0301 basic medicine, Oncology, PROTEIN, lcsh:Medicine, 45/47, 0302 clinical medicine, Fanconi anemia, Genotype, lcsh:Science, Sequence Deletion, Multidisciplinary, BRCA1 Protein, Fanconi Anemia Complementation Group C Protein, 1184 Genetics, developmental biology, physiology, BRCA2 Protein, 3. Good health, BIALLELIC MUTATIONS, DNA-REPAIR, Female, 692/499, Medical Genetics, medicine.medical_specialty, PALB2, 3122 Cancers, ABCTB Investigators, Breast Neoplasms, FANCONIS ANEMIA, Article, 692/4028, NBCS Collaborators, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, NONSENSE MUTATION, Genetic Predisposition to Disease, Medicinsk genetik, 45, business.industry, Genetic heterogeneity, lcsh:R, Case-control study, Genetic Variation, Odds ratio, medicine.disease, GENE, Fanconi Anemia, 030104 developmental biology, Risk factors, Case-Control Studies, lcsh:Q, 3111 Biomedicine, business, 030217 neurology & neurosurgery
Abstract

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

Published
2019
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35. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Author

Heemskerk-Gerritsen B.A.M., Ito H., Jakimovska M., Jakubowska A., Janni W., John E.M., Jung A., Kang D., Kets C.M., Khusnutdinova E., Ko Y.-D., Kristensen V.N., Kurian A.W., Kwong A., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Matsuo K., Mavroudis D., Meindl A., Milne R.L., Mulligan A.M., Muranen T.A., Neuhausen S.L., Nevanlinna H., Newman W.G., Olshan A.F., Olson J.E., Olsson H., Park-Simon T.-W., Peto J., Petridis C., Plaseska-Karanfilska D., Presneau N., Pylkas K., Radice P., Rennert G., Romero A., Roylance R., Saloustros E., Sawyer E.J., Schmutzler R.K., Schwentner L., Scott C., See M.-H., Shah M., Shen C.-Y., Shu X.-O., Siesling S., Slager S., Sohn C., Spinelli J.J., Stone J., Tapper W.J., Tengstrom M., Teo S.H., Terry M.B., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Vachon C.M., van Ongeval C., van Veen E.M., Winqvist R., Wolk A., Zheng W., Ziogas A., Easton D.F., Hall P., Schmidt M.K., Kramer I., Hooning M.J., Mavaddat N., Hauptmann M., Keeman R., Steyerberg E.W., Giardiello D., Antoniou A.C., Pharoah P.D.P., Canisius S., Abu-Ful Z., Andrulis I.L., Anton-Culver H., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Brauch H., Bremer M., Brucker S.Y., Burwinkel B., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Borresen-Dale A.-L., Sahlberg K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C., Reinertsen K., Helland A., Riis M., Geisler J., Alnaes G.G., Collee J.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Garcia-Closas M., Garcia-Saenz J.A., Giles G.G., Goldgar D.E., Gonzalez-Neira A., Haiman C.A., Hakansson N., Hamann U., Hartman M., Hollestelle A., Hopper J.L., Hou M.-F., Howell A., Clarke C., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Graham J.D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., deFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., McLachlan S.A., Meiser B., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., Young M.A., Heemskerk-Gerritsen B.A.M., Ito H., Jakimovska M., Jakubowska A., Janni W., John E.M., Jung A., Kang D., Kets C.M., Khusnutdinova E., Ko Y.-D., Kristensen V.N., Kurian A.W., Kwong A., Lambrechts D., Le Marchand L., Li J., Lindblom A., Lubinski J., Mannermaa A., Manoochehri M., Margolin S., Matsuo K., Mavroudis D., Meindl A., Milne R.L., Mulligan A.M., Muranen T.A., Neuhausen S.L., Nevanlinna H., Newman W.G., Olshan A.F., Olson J.E., Olsson H., Park-Simon T.-W., Peto J., Petridis C., Plaseska-Karanfilska D., Presneau N., Pylkas K., Radice P., Rennert G., Romero A., Roylance R., Saloustros E., Sawyer E.J., Schmutzler R.K., Schwentner L., Scott C., See M.-H., Shah M., Shen C.-Y., Shu X.-O., Siesling S., Slager S., Sohn C., Spinelli J.J., Stone J., Tapper W.J., Tengstrom M., Teo S.H., Terry M.B., Tollenaar R.A.E.M., Tomlinson I., Troester M.A., Vachon C.M., van Ongeval C., van Veen E.M., Winqvist R., Wolk A., Zheng W., Ziogas A., Easton D.F., Hall P., Schmidt M.K., Kramer I., Hooning M.J., Mavaddat N., Hauptmann M., Keeman R., Steyerberg E.W., Giardiello D., Antoniou A.C., Pharoah P.D.P., Canisius S., Abu-Ful Z., Andrulis I.L., Anton-Culver H., Aronson K.J., Augustinsson A., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Brauch H., Bremer M., Brucker S.Y., Burwinkel B., Castelao J.E., Chan T.L., Chang-Claude J., Chanock S.J., Chenevix-Trench G., Choi J.-Y., Clarke C.L., Borresen-Dale A.-L., Sahlberg K., Ottestad L., Karesen R., Schlichting E., Holmen M.M., Sauer T., Haakensen V., Engebraten O., Naume B., Fossa A., Kiserud C., Reinertsen K., Helland A., Riis M., Geisler J., Alnaes G.G., Collee J.M., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Evans D.G., Fasching P.A., Flyger H., Gago-Dominguez M., Garcia-Closas M., Garcia-Saenz J.A., Giles G.G., Goldgar D.E., Gonzalez-Neira A., Haiman C.A., Hakansson N., Hamann U., Hartman M., Hollestelle A., Hopper J.L., Hou M.-F., Howell A., Clarke C., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Graham J.D., Sachchithananthan M., Amor D., Andrews L., Antill Y., Balleine R., Beesley J., Bennett I., Bogwitz M., Botes L., Brennan M., Brown M., Buckley M., Burke J., Butow P., Caldon L., Campbell I., Chauhan D., Chauhan M., Christian A., Cohen P., Colley A., Crook A., Cui J., Cummings M., Dawson S.-J., deFazio A., Delatycki M., Dickson R., Dixon J., Edkins T., Edwards S., Farshid G., Fellows A., Fenton G., Field M., Flanagan J., Fong P., Forrest L., Fox S., French J., Friedlander M., Gaff C., Gattas M., George P., Greening S., Harris M., Hart S., Hayward N., Hopper J., Hoskins C., Hunt C., James P., Jenkins M., Kidd A., Kirk J., Koehler J., Kollias J., Lakhani S., Lawrence M., Lindeman G., Lipton L., Lobb L., Mann G., McLachlan S.A., Meiser B., Nightingale S., O'Connell S., O'Sullivan S., Ortega D.G., Pachter N., Patterson B., Pearn A., Phillips K., Pieper E., Rickard E., Robinson B., Saleh M., Salisbury E., Saunders C., Saunus J., Sexton A., Shelling A., Southey M.C., Spurdle A., Taylor J., Taylor R., Thorne H., Trainer A., Tucker K., Visvader J., Walker L., Williams R., Winship I., and Young M.A.

Abstract

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.Copyright © 2020 American Society of Human Genetics

Published
2020

36. The importance of the sampling frequency in determining short-time-averaged irradiance and illuminance for rapidly changing cloud cover

Author

Delaunay, J.J., Rommel, M., and Geisler, J.

Subjects
Solar radiation -- Measurement, Photometry -- Research, Daylight -- Measurement, Earth sciences, Petroleum, energy and mining industries
Abstract

The sampling interval is an important parameter which must be chosen carefully, if measurements of the direct, global, and diffuse irradiance or illuminance are carried out to determine their averages over a given period. Using measurements from a day with rapidly moving clouds, we investigated the influence of the sampling interval on the uncertainty of the calculated 15-min averages. We conclude, for this averaging period, that the sampling interval should not exceed 60 s and 10 s for measurement of the diffuse and global components respectively, to reduce the influence of the sampling interval below 2%. For the direct component, even a 5 s sampling interval is too long to reach this influence level for days with extremely quickly changing insolation conditions.

Published
1994

37. Neoadjuvant olaparib monotherapy in primary triple negative breast cancer

Author

Eikesdal, H.P., primary, Yndestad, S., additional, Blix, E.S., additional, Lundgren, S., additional, Vagstad, G., additional, Espelid, H., additional, Gilje, B., additional, Janssen, E.A., additional, Geisler, J., additional, Aas, T., additional, Aase, H., additional, Knappskog, S., additional, and Lønning, P.E., additional

Published
2019
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41. Abstract OT1-01-01: The NEO-LET-EXE-trial: An intra-patient cross-over trial to explore the "lack of cross-resistance" between steroidal and non-steroidal aromatase inhibitors

Author

Bahrami, N, primary, Sauer, T, additional, Loeng, M, additional, Gravdehaug, B, additional, Engebretsen, SS, additional, Aljabri, B, additional, Bemanian, V, additional, Lindstrøm, JC, additional, Lüders, T, additional, Kristensen, VN, additional, and Geisler, J, additional

Published
2019
Full Text
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43. Two truncating variants in FANCC and breast cancer risk

Author

Dork, T, Peterlongo, P, Mannermaa, A, Bolla, MK, Wang, Q, Dennis, J, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Beckmann, MW, Beeghly-Fadiel, A, Behrens, S, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Canzian, F, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Christiansen, H, Clarke, CL, Couch, FJ, Czene, K, Daly, MB, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Ekici, AB, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flyger, H, Fritschisl, L, Gabrielson, M, Gago-Dominguez, M, Gao, C, Gapstur, SM, Garcia-Closas, M, Garcia-Saenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Goldgar, DE, Guenel, P, Haeberle, L, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hartman, M, Hauke, J, Hein, A, Hillemanns, P, Hogervorst, FBL, Hooning, MJ, Hopper, JL, Howell, T, Huo, D, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kaaks, R, Kang, D, Kapoor, PM, Khusnutdinova, E, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kwon, A, Lambrechts, D, Le Marchand, L, Li, J, Lindstrom, S, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Lubinski, J, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, E, Matsuo, K, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Taib, NAM, Muir, K, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Offit, K, Olopade, O, Olshan, AF, Olson, JE, Olsson, H, Park, SK, Park-Simon, T-W, Peto, J, Plaseska-Karanfilska, D, Pohl-Rescigno, E, Presneau, N, Rack, B, Radice, P, Rashid, MU, Rennert, G, Rennert, HS, Romero, A, Ruebner, M, Saloustros, E, Schmidt, MK, Schmutzler, RK, Schneider, MO, Schoemaker, MJ, Scott, C, Shen, C-Y, Shu, X-O, Simard, J, Slager, S, Smichkoska, S, Southey, MC, Spinelli, JJ, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teo, SH, Terry, MB, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejia, G, Troester, MA, Truong, T, Tsugane, S, Untch, M, Vachon, CM, van den Ouweland, AMW, van Veen, EM, Vijai, J, Wendt, C, Wolk, A, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Dunning, AM, Pharoah, PDP, Schindler, D, Devilee, P, Easton, DF, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Borresen-Dale, A-L, Alnaes, GIG, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, Geisler, J, Dork, T, Peterlongo, P, Mannermaa, A, Bolla, MK, Wang, Q, Dennis, J, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Beckmann, MW, Beeghly-Fadiel, A, Behrens, S, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Canzian, F, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Christiansen, H, Clarke, CL, Couch, FJ, Czene, K, Daly, MB, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Ekici, AB, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flyger, H, Fritschisl, L, Gabrielson, M, Gago-Dominguez, M, Gao, C, Gapstur, SM, Garcia-Closas, M, Garcia-Saenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Goldgar, DE, Guenel, P, Haeberle, L, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hartman, M, Hauke, J, Hein, A, Hillemanns, P, Hogervorst, FBL, Hooning, MJ, Hopper, JL, Howell, T, Huo, D, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kaaks, R, Kang, D, Kapoor, PM, Khusnutdinova, E, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kwon, A, Lambrechts, D, Le Marchand, L, Li, J, Lindstrom, S, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Lubinski, J, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, E, Matsuo, K, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Taib, NAM, Muir, K, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Offit, K, Olopade, O, Olshan, AF, Olson, JE, Olsson, H, Park, SK, Park-Simon, T-W, Peto, J, Plaseska-Karanfilska, D, Pohl-Rescigno, E, Presneau, N, Rack, B, Radice, P, Rashid, MU, Rennert, G, Rennert, HS, Romero, A, Ruebner, M, Saloustros, E, Schmidt, MK, Schmutzler, RK, Schneider, MO, Schoemaker, MJ, Scott, C, Shen, C-Y, Shu, X-O, Simard, J, Slager, S, Smichkoska, S, Southey, MC, Spinelli, JJ, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teo, SH, Terry, MB, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejia, G, Troester, MA, Truong, T, Tsugane, S, Untch, M, Vachon, CM, van den Ouweland, AMW, van Veen, EM, Vijai, J, Wendt, C, Wolk, A, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Dunning, AM, Pharoah, PDP, Schindler, D, Devilee, P, Easton, DF, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Borresen-Dale, A-L, Alnaes, GIG, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, and Geisler, J

Abstract

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

Published
2019

44. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Author

Mavaddat, N, Michailidou, K, Dennis, J, Lush, M, Fachal, L, Lee, A, Tyrer, JP, Chen, T-H, Wang, Q, Bolla, MK, Yang, X, Adank, MA, Ahearn, T, Aittomaki, K, Allen, J, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Auer, PL, Auvinen, P, Barrdahl, M, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Bremer, M, Brenner, H, Brentnall, A, Brock, IW, Brooks-Wilson, A, Brucker, SY, Bruening, T, Burwinkel, B, Campa, D, Carter, BD, Castelao, JE, Chanock, SJ, Chlebowski, R, Christiansen, H, Clarke, CL, Collee, JM, Cordina-Duverger, E, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Foersti, A, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Gilyazova, IR, Glendon, G, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Gronwald, J, Grundy, A, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hankinson, SE, Harkness, EF, Hart, SN, He, W, Hein, A, Heyworth, J, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huang, G, Humphreys, K, Hunter, DJ, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, ME, Jukkola-Vuorinen, A, Jung, A, Kaaks, R, Kaczmarek, K, Kataja, V, Keeman, R, Kerin, MJ, Khusnutdinova, E, Kiiski, J, Knight, JA, Ko, Y-D, Kosma, V-M, Koutros, S, Kristensen, VN, Kruger, U, Kuehl, T, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Lilyquist, J, Lindblom, A, Lindstrom, S, Lissowska, J, Lo, W-Y, Loibl, S, Long, J, Lubinski, J, Lux, MP, MacInnis, RJ, Maishman, T, Makalic, E, Kostovska, IM, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, McLean, C, Meindl, A, Menon, U, Middha, P, Miller, N, Moreno, F, Mulligan, AM, Mulot, C, Munoz-Garzon, VM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, Offit, K, Olson, JE, Olsson, H, Orr, N, Pankratz, VS, Park-Simon, T-W, Perez, JIA, Perez-Barrios, C, Peterlongo, P, Peto, J, Pinchev, M, Plaseska-Karanfilska, D, Polley, EC, Prentice, R, Presneau, N, Prokofyeva, D, Purrington, K, Pylkas, K, Rack, B, Radice, P, Rau-Murthy, R, Rennert, G, Rennert, HS, Rhenius, V, Robson, M, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, DF, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schumacher, F, Schuermann, P, Schwentner, L, Scott, C, Scott, RJ, Seynaeve, C, Shah, M, Sherman, ME, Shrubsole, MJ, Shu, X-O, Slager, S, Smeets, A, Sohn, C, Soucy, P, Southey, MC, Spinelli, JJ, Stegmaier, C, Stone, J, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Thoene, K, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tzardi, M, Ulmer, H-U, Untch, M, Vachon, CM, van Veen, EM, Vijai, J, Weinberg, CR, Wendt, C, Whittemore, AS, Wildiers, H, Willett, W, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zhang, Y, Zheng, W, Ziogas, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Sexton, A, Dobrovic, A, Christian, A, Trainer, A, Fellows, A, Shelling, A, De Fazio, A, Blackburn, A, Crook, A, Meiser, B, Patterson, B, Saunders, C, Hunt, C, Amor, D, Ortega, DG, Edkins, E, Salisbury, E, Haan, E, Macrea, F, Farshid, G, Lindeman, G, Trench, G, Mann, G, Giles, G, Gill, G, Thorne, H, Campbell, I, Hickie, I, Caldon, L, Winship, I, Cui, J, Flanagan, J, Kollias, J, Visvader, J, Taylor, J, Burke, J, Saunus, J, Forbs, J, Hopper, J, Beesley, J, Kirk, J, French, J, Tucker, K, Wu, K, Phillips, K, Forrest, L, Lipton, L, Andrews, L, Lobb, L, Walker, L, Kentwell, M, Spurdle, M, Cummings, M, Gleeson, M, Harris, M, Jenkins, M, Young, MA, Delatycki, M, Wallis, M, Burgess, M, Brown, M, Southey, M, Bogwitz, M, Field, M, Friedlander, M, Gattas, M, Saleh, M, Aghmesheh, M, Hayward, N, Pachter, N, Cohen, P, Duijf, P, James, P, Fong, P, Butow, P, Williams, R, Kefford, R, Simard, J, Balleine, R-M, Dawson, S-J, Lok, S, O'connell, S, Greening, S, Nightingale, S, Edwards, S, Fox, S, McLachlan, S-A, Lakhani, S, Dudding, T, Antill, Y, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, Geisler, J, Dunning, AM, Thompson, DJ, Chenevix-Trench, G, Chang-Claude, J, Schmidt, MK, Hall, P, Milne, RL, Pharoah, PDP, Antoniou, AC, Chatterjee, N, Kraft, P, Garcia-Closas, M, Easton, DF, Mavaddat, N, Michailidou, K, Dennis, J, Lush, M, Fachal, L, Lee, A, Tyrer, JP, Chen, T-H, Wang, Q, Bolla, MK, Yang, X, Adank, MA, Ahearn, T, Aittomaki, K, Allen, J, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Auer, PL, Auvinen, P, Barrdahl, M, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Bremer, M, Brenner, H, Brentnall, A, Brock, IW, Brooks-Wilson, A, Brucker, SY, Bruening, T, Burwinkel, B, Campa, D, Carter, BD, Castelao, JE, Chanock, SJ, Chlebowski, R, Christiansen, H, Clarke, CL, Collee, JM, Cordina-Duverger, E, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Foersti, A, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Gilyazova, IR, Glendon, G, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Gronwald, J, Grundy, A, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hankinson, SE, Harkness, EF, Hart, SN, He, W, Hein, A, Heyworth, J, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huang, G, Humphreys, K, Hunter, DJ, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, ME, Jukkola-Vuorinen, A, Jung, A, Kaaks, R, Kaczmarek, K, Kataja, V, Keeman, R, Kerin, MJ, Khusnutdinova, E, Kiiski, J, Knight, JA, Ko, Y-D, Kosma, V-M, Koutros, S, Kristensen, VN, Kruger, U, Kuehl, T, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Lilyquist, J, Lindblom, A, Lindstrom, S, Lissowska, J, Lo, W-Y, Loibl, S, Long, J, Lubinski, J, Lux, MP, MacInnis, RJ, Maishman, T, Makalic, E, Kostovska, IM, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, McLean, C, Meindl, A, Menon, U, Middha, P, Miller, N, Moreno, F, Mulligan, AM, Mulot, C, Munoz-Garzon, VM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, Offit, K, Olson, JE, Olsson, H, Orr, N, Pankratz, VS, Park-Simon, T-W, Perez, JIA, Perez-Barrios, C, Peterlongo, P, Peto, J, Pinchev, M, Plaseska-Karanfilska, D, Polley, EC, Prentice, R, Presneau, N, Prokofyeva, D, Purrington, K, Pylkas, K, Rack, B, Radice, P, Rau-Murthy, R, Rennert, G, Rennert, HS, Rhenius, V, Robson, M, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, DF, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schumacher, F, Schuermann, P, Schwentner, L, Scott, C, Scott, RJ, Seynaeve, C, Shah, M, Sherman, ME, Shrubsole, MJ, Shu, X-O, Slager, S, Smeets, A, Sohn, C, Soucy, P, Southey, MC, Spinelli, JJ, Stegmaier, C, Stone, J, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Thoene, K, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tzardi, M, Ulmer, H-U, Untch, M, Vachon, CM, van Veen, EM, Vijai, J, Weinberg, CR, Wendt, C, Whittemore, AS, Wildiers, H, Willett, W, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zhang, Y, Zheng, W, Ziogas, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Sexton, A, Dobrovic, A, Christian, A, Trainer, A, Fellows, A, Shelling, A, De Fazio, A, Blackburn, A, Crook, A, Meiser, B, Patterson, B, Saunders, C, Hunt, C, Amor, D, Ortega, DG, Edkins, E, Salisbury, E, Haan, E, Macrea, F, Farshid, G, Lindeman, G, Trench, G, Mann, G, Giles, G, Gill, G, Thorne, H, Campbell, I, Hickie, I, Caldon, L, Winship, I, Cui, J, Flanagan, J, Kollias, J, Visvader, J, Taylor, J, Burke, J, Saunus, J, Forbs, J, Hopper, J, Beesley, J, Kirk, J, French, J, Tucker, K, Wu, K, Phillips, K, Forrest, L, Lipton, L, Andrews, L, Lobb, L, Walker, L, Kentwell, M, Spurdle, M, Cummings, M, Gleeson, M, Harris, M, Jenkins, M, Young, MA, Delatycki, M, Wallis, M, Burgess, M, Brown, M, Southey, M, Bogwitz, M, Field, M, Friedlander, M, Gattas, M, Saleh, M, Aghmesheh, M, Hayward, N, Pachter, N, Cohen, P, Duijf, P, James, P, Fong, P, Butow, P, Williams, R, Kefford, R, Simard, J, Balleine, R-M, Dawson, S-J, Lok, S, O'connell, S, Greening, S, Nightingale, S, Edwards, S, Fox, S, McLachlan, S-A, Lakhani, S, Dudding, T, Antill, Y, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, Geisler, J, Dunning, AM, Thompson, DJ, Chenevix-Trench, G, Chang-Claude, J, Schmidt, MK, Hall, P, Milne, RL, Pharoah, PDP, Antoniou, AC, Chatterjee, N, Kraft, P, Garcia-Closas, M, and Easton, DF

Abstract

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Published
2019

45. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

Author

Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), Easton, D. F. (Douglas F.), Mavaddat, N. (Nasim), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Lush, M. (Michael), Fachal, L. (Laura), Lee, A. (Andrew), Tyrer, J. P. (Jonathan P.), Chen, T.-H. (Ting-Huei), Wang, Q. (Qin), Bolla, M. K. (Manjeet K.), Yang, X. (Xin), Adank, M. A. (Muriel A.), Ahearn, T. (Thomas), Aittomaki, K. (Kristiina), Allen, J. (Jamie), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N. N. (Natalia N.), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Auvinen, P. (Paivi), Barrdahl, M. (Myrto), Freeman, L. E. (Laura E. Beane), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Bremer, M. (Michael), Brenner, H. (Hermann), Brentnall, A. (Adam), Brock, I. W. (Ian W.), Brooks-Wilson, A. (Angela), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Campa, D. (Daniele), Carter, B. D. (Brian D.), Castelao, J. E. (Jose E.), Chanock, S. J. (Stephen J.), Chlebowski, R. (Rowan), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, J. M. (J. Margriet), Cordina-Duverger, E. (Emilie), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doerk, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Durcan, L. (Lorraine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Ellberg, C. (Carolina), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foersti, A. (Asta), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Georgoulias, V. (Vassilios), Giles, G. G. (Graham G.), Gilyazova, I. R. (Irina R.), Glendon, G. (Gord), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Alnaes, G. I. (Grethe I. Grenaker), Grip, M. (Mervi), Gronwald, J. (Jacek), Grundy, A. (Anne), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hamann, U. (Ute), Hankinson, S. E. (Susan E.), Harkness, E. F. (Elaine F.), Hart, S. N. (Steven N.), He, W. (Wei), Hein, A. (Alexander), Heyworth, J. (Jane), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakimovska, M. (Milena), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, M. E. (Michael E.), Jukkola-Vuorinen, A. (Arja), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kaczmarek, K. (Katarzyna), Kataja, V. (Vesa), Keeman, R. (Renske), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kiiski, J. I. (Johanna, I), Knight, J. A. (Julia A.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Kruger, U. (Ute), Kuehl, T. (Tabea), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lee, E. (Eunjung), Lejbkowicz, F. (Flavio), Lilyquist, J. (Jenna), Lindblom, A. (Annika), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Long, J. (Jirong), Lubinski, J. (Jan), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Makalic, E. (Enes), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), McLean, C. (Catriona), Meindl, A. (Alfons), Menon, U. (Usha), Middha, P. (Pooja), Miller, N. (Nicola), Moreno, F. (Fernando), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Munoz-Garzon, V. M. (Victor M.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Norman, A. (Aaron), Offit, K. (Kenneth), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Orr, N. (Nick), Pankratz, V. S. (V. Shane), Park-Simon, T.-W. (Tjoung-Won), Perez, J. I. (Jose I. A.), Perez-Barrios, C. (Clara), Peterlongo, P. (Paolo), Peto, J. (Julian), Pinchev, M. (Mila), Plaseska-Karanfilska, D. (Dijana), Polley, E. C. (Eric C.), Prentice, R. (Ross), Presneau, N. (Nadege), Prokofyeva, D. (Darya), Purrington, K. (Kristen), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Robson, M. (Mark), Romero, A. (Atocha), Ruddy, K. J. (Kathryn J.), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, D. F. (Daniel F.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schumacher, F. (Fredrick), Schuermann, P. (Peter), Schwentner, L. (Lukas), Scott, C. (Christopher), Scott, R. J. (Rodney J.), Seynaeve, C. (Caroline), Shah, M. (Mitul), Sherman, M. E. (Mark E.), Shrubsole, M. J. (Martha J.), Shu, X.-O. (Xiao-Ou), Slager, S. (Susan), Smeets, A. (Ann), Sohn, C. (Christof), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stegmaier, C. (Christa), Stone, J. (Jennifer), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Thoene, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Truong, T. (Therese), Tzardi, M. (Maria), Ulmer, H.-U. (Hans-Ulrich), Untch, M. (Michael), Vachon, C. M. (Celine M.), van Veen, E. M. (Elke M.), Vijai, J. (Joseph), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. (Walter), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zhang, Y. (Yan), Zheng, W. (Wei), Ziogas, A. (Argyrios), Clarke, C. (Christine), Balleine, R. (Rosemary), Baxter, R. (Robert), Braye, S. (Stephen), Carpenter, J. (Jane), Dahlstrom, J. (Jane), Forbes, J. (John), Lee, C. S. (C. Soon), Marsh, D. (Deborah), Morey, A. (Adrienne), Pathmanathan, N. (Nirmala), Scott, R. (Rodney), Simpson, P. (Peter), Spigelman, A. (Allan), Wilcken, N. (Nicholas), Yip, D. (Desmond), Zeps, N. (Nikolajs), Sexton, A. (Adrienne), Dobrovic, A. (Alex), Christian, A. (Alice), Trainer, A. (Alison), Fellows, A. (Andrew), Shelling, A. (Andrew), De Fazio, A. (Anna), Blackburn, A. (Anneke), Crook, A. (Ashley), Meiser, B. (Bettina), Patterson, B. (Briony), Clarke, C. (Christobel), Saunders, C. (Christobel), Hunt, C. (Clare), Scott, C. (Clare), Amor, D. (David), Ortega, D. G. (David Gallego), Marsh, D. (Deb), Edkins, E. (Edward), Salisbury, E. (Elizabeth), Haan, E. (Eric), Macrea, F. (Finlay), Farshid, G. (Gelareh), Lindeman, G. (Geoff), Trench, G. (Georgia), Mann, G. (Graham), Giles, G. (Graham), Gill, G. (Grantley), Thorne, H. (Heather), Campbell, I. (Ian), Hickie, I. (Ian), Caldon, L. (Liz), Winship, I. (Ingrid), Cui, J. (James), Flanagan, J. (James), Kollias, J. (James), Visvader, J. (Jane), Taylor, J. (Jessica), Burke, J. (Jo), Saunus, J. (Jodi), Forbs, J. (John), Hopper, J. (John), Beesley, J. (Jonathan), Kirk, J. (Judy), French, J. (Juliet), Tucker, K. (Kathy), Wu, K. (Kathy), Phillips, K. (Kelly), Forrest, L. (Laura), Lipton, L. (Lara), Andrews, L. (Leslie), Lobb, L. (Lizz), Walker, L. (Logan), Kentwell, M. (Maira), Spurdle, M. (Mandy), Cummings, M. (Margaret), Gleeson, M. (Margaret), Harris, M. (Marion), Jenkins, M. (Mark), Young, M. A. (Mary Anne), Delatycki, M. (Martin), Wallis, M. (Mathew), Burgess, M. (Matthew), Brown, M. (Melissa), Southey, M. (Melissa), Bogwitz, M. (Michael), Field, M. (Michael), Friedlander, M. (Michael), Gattas, M. (Michael), Saleh, M. (Mona), Aghmesheh, M. (Morteza), Hayward, N. (Nick), Pachter, N. (Nick), Cohen, P. (Paul), Duijf, P. (Pascal), James, P. (Paul), Simpson, P. (Pete), Fong, P. (Peter), Butow, P. (Phyllis), Williams, R. (Rachael), Kefford, R. (Rick), Simard, J. (Jacques), Balleine, R.-M. (Rose-Mary), Dawson, S.-J. (Sarah-Jane), Lok, S. (Sheau), O'connell, S. (Shona), Greening, S. (Sian), Nightingale, S. (Sophie), Edwards, S. (Stacey), Fox, S. (Stephen), McLachlan, S.-A. (Sue-Anne), Lakhani, S. (Sunil), Dudding, T. (Tracy), Antill, Y. (Yoland), Sahlberg, K. K. (Kristine K.), Ottestad, L. (Lars), Karesen, R. (Rolf), Schlichting, E. (Ellen), Holmen, M. M. (Marit Muri), Sauer, T. (Toril), Haakensen, V. (Vilde), Engebraten, O. (Olav), Naume, B. (Bjorn), Fossa, A. (Alexander), Kiserud, C. E. (Cecile E.), Reinertsen, K. V. (Kristin, V), Helland, A. (Aslaug), Riis, M. (Margit), Geisler, J. (Juergen), Dunning, A. M. (Alison M.), Thompson, D. J. (Deborah J.), Chenevix-Trench, G. (Georgia), Chang-Claude, J. (Jenny), Schmidt, M. K. (Marjanka K.), Hall, P. (Per), Milne, R. L. (Roger L.), Pharoah, P. D. (Paul D. P.), Antoniou, A. C. (Antonis C.), Chatterjee, N. (Nilanjan), Kraft, P. (Peter), Garcia-Closas, M. (Montserrat), and Easton, D. F. (Douglas F.)

Abstract

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Published
2019

46. The NAME trial: A direct comparison of oral navelbine given either classic or metronomic in metastatic HER2 neg breast cancer

Author

Langkjer, S.T., primary, Kenholm, J., additional, Jensen, J.D., additional, Wedervang, K., additional, Brixen, A.T., additional, Grunnet, M., additional, Stenbygaard, L., additional, Danø, H., additional, Glavicic, V., additional, Jacobsen, E.H., additional, Brems-Eskildsen, A.S., additional, Kruse, H.L., additional, Dongsgaard, T., additional, Neimann, J., additional, and Geisler, J., additional

Published
2018
Full Text
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47. Patterns of genomic evolution in advanced melanoma

Author

Birkeland, E., primary, Zhang, S., additional, Poduval, D., additional, Geisler, J., additional, Nakken, S., additional, Vodak, D., additional, Meza-Zepeda, L. A., additional, Hovig, E., additional, Myklebost, O., additional, Knappskog, S., additional, and Lønning, P. E., additional

Published
2018
Full Text
View/download PDF

48. Finishing of wood machined surfaces. Which characteristics for which performance?

Author

Ramanakoto, M., Eyma, Florent, Ramananantoandro, T., Geisler, J., Castanié, Bruno, Institut Clément Ader (ICA), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IMT École nationale supérieure des Mines d'Albi-Carmaux (IMT Mines Albi), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-IMT École nationale supérieure des Mines d'Albi-Carmaux (IMT Mines Albi), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
[PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2017

49. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

Author

Gulati, G., Heck, S.L., Ree, A.H., Hoffmann, P., Schulz-Menger, J., Fagerland, M.W., Gravdehaug, B., von Knobelsdorff-Brenkenhoff, F., Bratland, Å., Storås, T.H., Hagve, T.A., Røsjø, H., Steine, K., Geisler, J., and Omland, T.

Subjects
Cardiovascular and Metabolic Diseases, cardiovascular diseases
Abstract

Aims: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the {beta}-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results: In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the {beta}-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.

Published
2016

50. Collage et finition des surfaces bois usinées. Quelles caractéristiques pour quelles performances?

Author

Ramanakoto, M., Eyma, Florent, Ramananantoandro, T., Geisler, J., Castanié, Bruno, Institut Clément Ader (ICA), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IMT École nationale supérieure des Mines d'Albi-Carmaux (IMT Mines Albi), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-IMT École nationale supérieure des Mines d'Albi-Carmaux (IMT Mines Albi), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
[PHYS]Physics [physics], ComputingMethodologies_GENERAL, [PHYS.MECA]Physics [physics]/Mechanics [physics], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Prix du meilleur poster

Published
2016

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