title: Loss of heterozygosity at the CYP2D6 locus in breast cancer: implications for germline pharmacogenetic studies.
abstract: BACKGROUND
  Controversy 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.
  
  
  METHODS
  Genomic 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  LOH 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.
authors.affiliation: Department 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.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Goetz
authors.affiliation: Department 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.
authors.forename: James X
authors.initials: JX
authors.lastname: Sun
authors.affiliation: Department 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.
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.affiliation: Department 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.
authors.forename: Grace O
authors.initials: GO
authors.lastname: Silva
authors.affiliation: Department 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.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Department 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.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department 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.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Department 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.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Department 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.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Department 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.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Department 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.
authors.forename: David
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department 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.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Safgren
authors.affiliation: Department 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.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Kuffel
authors.affiliation: Department 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.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ames
authors.affiliation: Department 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.
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Kalari
authors.affiliation: Department 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.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gomez
authors.affiliation: Department 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.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.affiliation: Department 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.
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgues
authors.affiliation: Department 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.
authors.forename: Hiltrud B
authors.initials: HB
authors.lastname: Brauch
authors.affiliation: Department 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.
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Department 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.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.affiliation: Department 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.
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005557:Formaldehyde; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009061:Mouth Mucosa; D016612:Paraffin Embedding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D016707:Tissue Fixation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019389:Cytochrome P-450 CYP2D6; D004273:DNA, Neoplasm; D005557:Formaldehyde; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; C508053:ERBB2 protein, human