ArticleNPJ breast cancer2025
Lessons learned from a candidate gene study investigating aromatase inhibitor treatment outcome in breast cancer.
Abstract read
In one paragraph
Article in NPJ breast cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
74 authors.
Reiner Hoppe *Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. reiner.hoppe@ikp-stuttgart.de.ORCID http://orcid.org/0000-0003-2213-9612
Stefan Winter *Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
Wing-Yee LoDepartment of Clinical Pathology, Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.
Kyriaki MichailidouBiostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.ORCID http://orcid.org/0000-0001-7065-1237
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-4351-9326
Renske KeemanDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-5452-9933
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4591-1214
Michael LushCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Krishna R KalariDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Matthew P GoetzDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4383-270X
Liewei WangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-3818-8531
Junmei CairnsDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Richard WeinshilboumDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4911-7985
Lois ShepherdCanadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada.
Bingshu E ChenCanadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada.ORCID http://orcid.org/0000-0001-6139-0696
Lothar HäberleDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Matthias RuebnerDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Matthias W BeckmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Wei HeDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Nicole L LarsonDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
Sebastian M ArmasuDepartment of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA.
Werner SchrothDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
Balram ChowbayLaboratory of Clinical Pharmacology, Division of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore, Singapore.
Chiea Chuen KhorGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-1128-4729
Mustapha AbubakarDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3728-6535
Antonis C AntoniouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Thomas BrüningInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany.
Jose E CastelaoOncology and Genetics Unit, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) Foundation, Complejo Hospitalario Universitario de Santiago, SERGAS, Vigo, Spain.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8919-1971
Nbcs CollaboratorsDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
Thilo DörkGynaecology Research Unit, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0002-9458-0282
Diana M EcclesFaculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0002-9935-3169
Jonine D FigueroaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5100-623X
Manuela Gago-DominguezCancer Genetics and Epidemiology Group, Genomic Medicine Group, Fundación Pública Galega de Medicina Xenómica, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.
José A García-SáenzMedical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.ORCID http://orcid.org/0000-0001-6880-0301
Melanie GündertMolecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Carolin C HackDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Ute HamannMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sileny HanLeuven Multidisciplinary Breast Center, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Maartje J HooningDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Hanna HuebnerDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.ORCID http://orcid.org/0000-0001-6889-1493
Abctb InvestigatorsAustralian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Esther M JohnDepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
Yon-Dschun KoDepartment of Internal Medicine, Johanniter GmbH Bonn, Johanniter Krankenhaus, Bonn, Germany.
Vessela N KristensenDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID http://orcid.org/0000-0001-5012-7438
Sabine LinnDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5541-0347
Sara MargolinDepartment of Oncology, Södersjukhuset, Stockholm, Sweden.
Dimitrios MavroudisDepartment of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
Heli NevanlinnaDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-0916-2976
Patrick NevenLeuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Nadia ObiInstitute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Tjoung-Won Park-SimonGynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Katri PylkäsLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, Medical Research Centre, University of Oulu, Oulu, Finland.
Muhammad U RashidMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7684-3122
Atocha RomeroMedical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.ORCID http://orcid.org/0000-0002-1634-7397
Emmanouil SaloustrosDepartment of Oncology, University Hospital of Larissa, Larissa, Greece.ORCID http://orcid.org/0000-0002-0485-0120
Elinor J SawyerSchool of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, UK.ORCID http://orcid.org/0000-0001-8285-4111
William J TapperFaculty of Medicine, University of Southampton, Southampton, UK.
Ian TomlinsonDepartment of Oncology, University of Oxford, Oxford, UK.
Camilla WendtDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Robert WinqvistLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, Biocenter Oulu, Medical Research Centre, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0003-0932-9104
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-6651-7166
Jacques SimardGenomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, Québec, Canada.ORCID http://orcid.org/0000-0001-6906-3390
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-5640-9126
Paul D P PharoahDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, CA, USA.ORCID http://orcid.org/0000-0001-8494-732X
Matthias SchwabDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.ORCID http://orcid.org/0000-0002-9984-075X
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.ORCID http://orcid.org/0000-0003-4885-8471
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-2444-3247
Marjanka K SchmidtDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-2228-429X
James N IngleDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1257-7731
Hiltrud BrauchDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.ORCID http://orcid.org/0000-0001-7531-2736
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Lila J. Rutten · 1985 to 2026
$151.3MThe Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9MNCIC Clinical Trials Group - Canadian Collaborating Clinical Trials NetworkU10CA180863 · NCI · QUEEN'S UNIVERSITY AT KINGSTON · PI Janet Ellen Dancey · 2014 to 2026
$40.4MCore-001U01CA164920 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Irene Andrulis, Sarah Violet Colonna · 2018 to 2026
$17.0MPharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8MNCIC Foreign AccrualsU10CA077202 · NCI · QUEEN'S UNIVERSITY AT KINGSTON · PI EISENHAUER, ELIZABETH · 1998 to 2013
$14.6MEpidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6MEpidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4MOvarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2MRisk and penetrance of mutations from breast cancer testing panels.R01CA192393 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH, NATHANSON, KATHERINE L. · 2014 to 2018
$6.3MResolving the cancer relevance of predisposition gene mutationsR35CA253187 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2020 to 2026
$5.8MA genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8MBreast Cancer Campaign 2010PR62Breast Cancer Campaign 2013PR044Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KH040Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KW0114Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KW9975/5Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KW9976/8Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KW9977/0Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) BMBF 01ZP0502Canadian Cancer Society Research Institute (Société Canadienne du Cancer) CCS 015469Cancer Research UK (CRUK) C12292/A11174Cancer Research UK (CRUK) C1275/A11699Cancer Research UK (CRUK) C1275/A15956Cancer Research UK (CRUK) C1275/A19187Cancer Research UK (CRUK) C1275/C22524Cancer Research UK (CRUK) C1281/A12014Cancer Research UK (CRUK) C1287/A10118Cancer Research UK (CRUK) C1287/A10710Cancer Research UK (CRUK) C1287/A16563Cancer Research UK (CRUK) C5047/A10692Cancer Research UK (CRUK) C5047/A15007Cancer Research UK (CRUK) C5047/A8384Cancer Research UK (CRUK) C8197/A16565Cancer Research UK (CRUK) PPRPGM-Nov20\100002Deutsche Forschungsgemeinschaft (German Research Foundation) DFG Do761/15-1Deutsche Forschungsgemeinschaft (German Research Foundation) EXC 2180-390900677Deutsche Forschungsgemeinschaft (German Research Foundation) SCHR 1323/2-1Deutsche Krebshilfe (German Cancer Aid) 106332Deutsche Krebshilfe (German Cancer Aid) 108253Deutsche Krebshilfe (German Cancer Aid) 108419Deutsche Krebshilfe (German Cancer Aid) 110826Deutsche Krebshilfe (German Cancer Aid) 110828Deutsche Krebshilfe (German Cancer Aid) 70-2892-BR IEC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health) HEALTH-F2-2009-223175MOH | National Medical Research Council (NMRC) MOH-000377MOH | National Medical Research Council (NMRC) MOH-000984MOH | National Medical Research Council (NMRC) NMRC/CIRG/1423/2015NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA116167NCI NIH HHS R01 CA128978NCI NIH HHS R01 CA176785NCI NIH HHS R01 CA192393NCI NIH HHS R01 CA196648NCI NIH HHS R35 CA253187NCI NIH HHS U01 CA164920NCI NIH HHS U10 CA077202NCI NIH HHS U10 CA180863NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148537NIGMS NIH HHS U19 GM061388
Abstract
The role of germline genetics in adjuvant aromatase inhibitor (AI) treatment efficacy in ER-positive breast cancer is poorly understood. We employed a two-stage candidate gene approach to examine associations between survival endpoints and common germline variants in 753 endocrine resistance-related genes. For a discovery cohort, we screened the Breast Cancer Association Consortium database (n ≥ 90,000 cases) and retrieved 2789 AI-treated patients. Cox model-based analysis revealed 125 variants associated with overall, distant relapse-free, and relapse-free survival (p-value ≤ 1E-04). In validation analysis using five independent cohorts (n = 8857), none of the six selected candidates representing major linkage blocks at CELA2B/CASP9, NR1I2/GSK3B, LRP1B, and MIR143HG (CARMN) were validated. We discuss potential reasons for the failed validation and replication of published findings, including study/treatment heterogeneity and other limitations inherent to genomic treatment outcome studies. For the future, we envision prospective longitudinal studies with sufficiently long follow-up and endpoints that reflect the dynamic nature of endocrine resistance.
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.