ArticleJournal of the National Cancer Institute2014
Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies.
Open access · greenAbstract read
In one paragraph
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 4 pooled it
2.7field-weighted citation impact, top 10% of its field
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
19 citing papers in PubMed, 4 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.Clinical pharmacology and therapeutics · 2018Guideline
- Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.The pharmacogenomics journal · 2018Pooled it
- Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity.American journal of epidemiology · 2017Pooled it
- Fc-gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer.Cancer medicine · 2018Trial
- Toxicity profile and clinical outcomes of stereotactic body radiotherapy with a focal boost without fiducials or perirectal hydrogel spacer for localized prostate cancer.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025Article
- Sequencing of genes of drug response in tumor DNA and implications for precision medicine in cancer patients.The pharmacogenomics journal · 2023Article
- Single-nucleotide polymorphisms and the effectiveness of taxane-based chemotherapy in premenopausal breast cancer: a population-based cohort study in Denmark.Breast cancer research and treatment · 2022Article
- Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450.Journal of personalized medicine · 2020Review
- Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.Journal of cancer research and clinical oncology · 2020Review
- Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Non-Journal of clinical medicine · 2019Article
- Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy.The oncologist · 2019Article
- CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.Cancer causes & control : CCC · 2019Article
- Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People.Clinical and translational science · 2018Article
- Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study.Breast cancer research : BCR · 2017Article
- CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study.Breast cancer research and treatment · 2017Article
- Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses.Molecular oncology · 2015Article
- Effects of Pharmacogenetics on the Pharmacokinetics and Pharmacodynamics of Tamoxifen.Clinical pharmacokinetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Matthew P GoetzDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
James X SunDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Vera J SumanDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Grace O SilvaDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Charles M PerouDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Yusuke NakamuraDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Nancy J CoxDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Philip J StephensDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Vincent A MillerDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Jeffrey S RossDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
David ChenDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Stephanie L SafgrenDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Mary J KuffelDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Matthew M AmesDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Krishna R KalariDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Henry L GomezDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Ana M Gonzalez-AnguloDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Octavio BurguesDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Hiltrud B BrauchDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
James N IngleDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Mark J RatainDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Roman YelenskyDepartment of Oncology (MPG, MMA, JNI), Department of Health Sciences Research (VJS, KRK), and Department of Molecular Pharmacology and Experimental Therapeutics (MPG, SLS, MK, MMA), Mayo Clinic, Rochester, MN; Department of Genetics, University of North Carolina, Chapel Hill, NC (GOS, CMP); Center for Personalized Therapeutics, University of Chicago, Chicago, IL (YN, NJC, MJR); Foundation Medicine Inc., Cambridge, MA (JXS, PJS, VAM, JSR, RY); Novartis Pharmaceuticals Corporation, East Hanover, NJ (DC); Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY (JSR); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (HG); Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (AMGA, OB); Department Breast Cancer Susceptibility and Pharmacogenomics, Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, University Tuebingen, German Cancer Consortium (DKTK) and German Cancer Research (DKTK), Heidelberg, Germany (HB).Current affiliation of H. Gomez: Departamento de Medicina Oncologica, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
Mayo Clinic · USEmergency Medicine Foundation · USFoundation Medicine (United States)The University of Texas MD Anderson Cancer Center · USUniversity of Chicago · USVanderbilt University · US
Funding
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MStatistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0MTissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KATHERINE A. HOADLEY · 1992 to 2026
$59.3MThe Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9MTISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7MWhole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI DOLAN, MARY EILEEN · 2000 to 2014
$39.0MTHE ALLIANCE NCTN BIOREPOSITORY AND BIOSPECIMEN RESOURCEU24CA196171 · NCI · WASHINGTON UNIVERSITY · PI Mine Cicek, Wendy Frankel · 2015 to 2026
$35.0MRe-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2MNCTN Lead Academic Participating Sites ApplicationU10CA180838 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CAREY, LISA A · 2014 to 2018
$2.8MTamoxifen biotransformation pathway pharmacogenomicsR01CA133049 · NCI · MAYO CLINIC ROCHESTER · PI GOETZ, MATTHEW PHILIP · 2008 to 2013
$2.3MNCATS NIH HHS UL1 TR000430NCI NIH HHS 1R01CA133049-01NCI NIH HHS CA058223NCI NIH HHS CA116201NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA058223NCI NIH HHS P50 CA098131NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180838NCI NIH HHS U10 CA180882NCI NIH HHS U24 CA196171NIGMS NIH HHS U01GM61393
Abstract
backgroundControversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined loss of heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source.
methodsGenomic tumor data from the adjuvant and metastatic settings (The Cancer Genome Atlas [TCGA] and Foundation Medicine [FM]) were analyzed to characterize the impact of CYP2D6 copy number alterations (CNAs) and LOH on Hardy Weinberg equilibrium (HWE). Additionally, we analyzed CYP2D6 *4 genotype from formalin-fixed paraffin-embedded (FFPE) tumor blocks containing nonmalignant tissue and buccal (germline) samples from patients on the North Central Cancer Treatment Group (NCCTG) 89-30-52 tamoxifen trial. All statistical tests were two-sided.
resultsIn TCGA samples (n =627), the CYP2D6 LOH rate was similar in estrogen receptor (ER)-positive (41.2%) and ER-negative (35.2%) but lower in HER2-positive tumors (15.1%) (P < .001). In FM ER+ samples (n = 290), similar LOH rates were observed (40.8%). In 190 NCCTG samples, the agreement between CYP2D6 genotypes derived from FFPE tumors and FFPE tumors containing nonmalignant tissue was moderate (weighted Kappa = 0.74; 95% CI = 0.63 to 0.84). Comparing CYP2D6 genotypes derived from buccal cells to FFPE tumor DNA, CYP2D6*4 genotype was discordant in six of 31(19.4%). In contrast, there was no disagreement between CYP2D6 genotypes derived from buccal cells with FFPE tumors containing nonmalignant tissue.
conclusionsLOH at the CYP2D6 locus is common in breast cancer, resulting in potential misclassification of germline CYP2D6 genotypes. Tumor DNA should not be used to determine germline CYP2D6 genotype without sensitive techniques to detect low frequency alleles and quality control procedures appropriate for somatic DNA.
Indexed as
Loss of HeterozygosityAdultAgedAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsCytochrome P-450 CYP2D6Disease-Free SurvivalDNA, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleFormaldehydeGenotypeHumansMiddle AgedMouth MucosaAntineoplastic Agents, HormonalBiomarkers, TumorCytochrome P-450 CYP2D6DNA, NeoplasmERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesFormaldehydeReceptors, EstrogenTamoxifen
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