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Prof. Dr. Hiltrud Beatrix Brauch

Affiliation

Margarete Fischer-Bosch-Institute of Clinical Pharmacology (IKP)
Deputy Head of the IKP
Section Head of the Department Breast Cancer Susceptibility and Pharmacogenomics

Auerbachstr. 112
D-70376 Stuttgart, Germany

Phone: +49 (0) 711 - 8101 3705
Fax: +49 (0) 711 - 859 295
e-mail: hiltrud.brauch@ikp-stuttgart.de

Prof. Hiltrud Brauch came to the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology (IKP) in 1999 after completing her training in Molecular Genetics of Cancer and Habilitation in the field of Molecular Pathology. She has held positions of increasing responsibility at the National Cancer Institute (NCI), USA, the German Cancer Research Center, Heidelberg, the Technical University Munich (Klinikum rechts der Isar), the University of Hamburg, and the IKP Stuttgart.

During her postdoctoral training at the NCI, she was part of the team identifying the VHL Tumor Suppressor Locus and since then pursues a range of scientific interests including the Molecular Origin of Hereditary (VHL disease) and Sporadic Kidney Cancer. Within the last decade she has established a reputation within the field of Breast Cancer Susceptibility and Treatment Outcomes. At IKP she has expanded her research towards a strong focus on the Pharmacogenomics of Breast Cancer.

Prof. Brauch participates in a number of national and international research networks including the Gene Environment Interactions and Breast Cancer in Germany (GENICA), the Breast Cancer Association Consortium (BCAC) and the International Tamoxifen Consortium (ITPC). She coordinated the 5FP EU European Marie Curie PhD training site Stuttgart/Tübingen “Fighting Breast Cancer”, and teaches at the University of Tübingen. Currently she coordinates the 7FP EU Initial Training Network Fighting Drug Failure, which establishes the first European Curriculum in the field of Pharmacogenomics for young investigators.

Scientific accomplishments include more than 150 peer reviewed publications, including more than 220 original research articles.

Academic Education and Professional Career

  • 1975 - 1981
    Study of Chemistry, University Fridericiana Karlsruhe (TH) , Germany
  • 1981 - 1985
    Dissertation, Institute of Immunology and Serology, Ruprecht Karls University Heidelberg, Germany
  • 1985 - 1989
    Visiting Fellow, Laboratory of Immunobiology (LIB)-National Cancer Institute (NCI)-National Institutes of Health (NIH), Frederick Cancer
    Research and Development Center (FCRDC)
    , Frederick, MD, USA 
  • 1989 - 1990
    Scientist, LIB, PRI-Inc. NCI-FCRDC, Frederick, MD, USA
  • 1990 - 1992
    Scientist, German Cancer Research Center (DKFZ), Germany
  • 1992 - 1996
    Section Head, Laboratory of Molecular Pathology, Institute of Pathology and Pathological Anatomy, Klinikum rechts der Isar, Technical University Munich, Germany
    Habilitation and Venia Legendi in Molecular Pathology
  • 1996 - 1999
    Head of Research Laboratory and Gynecological Diagnostics, Womens Hospital Eppendorf, University of Hamburg, Germany
    Venia Legendi in Molecular Biology
  • 1999 -
    Section Head Molecular Mechanisms of Origin and Treatment of Breast Cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart
  • 2000
    Venia Legendi in Molecular Pathology
  • 2006
    Extraordinary Professorship at the University Tübingen Medical School
  • Since 2008
    Deputy Head of the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Section Head of Breast Cancer Susceptibility and Pharmacogenomics, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Germany

Fellowship

  • 1985
    Forgarty international Visiting Fellowship, Program of Collaborative Research Experience in the United States, The National Institutes of Health (NIH), USA

Contents and Research Group

Can breast cancer risk, disease and drug treatment outcome be explained by genetic variation?

The high morbidity and mortality rates among breast cancer patients are mainly attributed to the lack of known risk factors as well as lack of efficient and non-toxic anti-cancer drugs. To improve women’s health and in particular to improve the quality of life of breast cancer patients, efficient approaches must include strategies for breast cancer prevention and improvement of individual drug therapy and response. My research team, therefore, focuses on the translation of basic research findings towards breast cancer prevention and the improvement of drug therapy, particular endocrine treatment. This involves laboratory and clinical investigations with defined patient collections, including case-control and treatment cohorts by way of candidate gene approaches, which currently focus on variations of drug metabolizing enzymes. This translational research involves a high degree of interdisciplinary collaboration among scientists with clinical, research and statistical expertise for the complex evaluation of clinical and laboratory data obtained via high-throughput molecular analyses.

Major projects

  • Genetic Variation and Breast Cancer Risk
  • Pharmacogenomics of Tamoxifen and other Endocrine Treatment
  • Target Identification for Breast Cancer Therapy
  • Clinical Sample Collections and Biobanking
  • Pharmacogenomic Curriculum Fighting Breast Cancer

Group Members

Research Scientists

  • Werner Schroth, PhD
  • Reiner Hoppe, PhD

Medical Doctor

  • Lisa Bacchus, MD

ITN Project Manager

  • Agapi Theodoridou MSc

Experienced Researcher (ER)

  • Wing-Yee Lo PhD

PhD Students (ESR)

  • Joanna Achinger, Ofure Akhibi,  Pilar Saladores

Former PhD Students trained within Marie Curie Program

  • Malgorzata Jaremko, PhD 2007 (current appointment: Mount Sinai, New York)
  • Zsuzanna Szabo, 2007 (current appointment: Maternity, University Debrecin)
  • Matjaz Rokavec, PhD 2008 (current appointment: Scripps, Florida)
  • Irena Andonova, PhD 2009 (current appointment: University Sofia)
  • Sandra Margarida Caldas Amaral, PhD 2010, (current appointment: University Lisboa)
  • Stefan Bozhanov (current appointment: University Sofia)

Study Nurse

  • Jasmin Happle

Technicians

  • Jana Ihring

Networks and Collaboration

Research

  • Since 1999
    Coordinator and Principle Investigator (PI) of the Research Network: The Interdisciplinary Study Group on Gene ENvironment Interactions and Breast CAncer in Germany (GENICA) for the identification of breast cancer susceptibility genes
  • 2005 - 2009
    Head of the Steering Committee and PI within the MARIE-GENICA Consortium for the identification of constitutional factors predictive for the risk to develop breast cancer following hormone replacement therapy (MARIE: MAmmakarzinom Risikofaktoren-Erhebung)
  • Since 2005
    Project Leader within the Network: Improvement of Breast Cancer Diagnosis and Treatment Tübingen-Stuttgart
  • Since 2005
    Member of the International Breast Cancer Association Consortium (BCAC) for the identification of breast cancer susceptibility genes
  • Since 2007
    Member of the Steering Committee International Tamoxifen Pharmacogenomics Consortium
  • Since 2007
    Member of the Scientific Advisory Board of the VHL Family Alliance Germany (Verein für von der von Hippel-Lindau (VHL) Erkrankung betroffene Familien e.V.)

European Marie Curie Actions

  • 2001 - 2005
    5FP: Coordinator Marie Curie Training Site Stuttgart/Tübingen: "Fighting Breast Cancer" - PhD Training Program
  • 2009-2013
    7FP: Coordinator of PEOPLE-Initial Training Network (ITN) "FightingDrugFailure" - PhD and young investigator training within dedicated research projects

Professional Memberships

Societies

American Association of Cancer Research (AACR)

AACR-Molecular Epidemiology Group (MEG)

AACR-Women in Cancer Research (WICR)

American Society of Human Genetics (ASHG)

Gesellschaft für Biochemie und Molekularbiologie (GBM

Editorial Board

Pharmacogenetics and Genomics

Conference Organization

Cold Spring Harbor Laboratory Conference Pharmacogenomics & Personalized Medicine

Extramural Funding

Bundesministerium für Bildung und Forschung (BMBF)

European Union (FP5, FP7)

Selected peer-reviewed publications

Selected peer-reviewed publications

Breast Cancer Pharmacogenomic

Province MA, Goetz MP, Brauch H, et al. CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations. Clin Pharmacol Ther. 2014 Feb;95(2):216-27.

Garcia-Closas M, Couch FJ, Lindstrom S, et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet. 2013 Apr;45(4):392-8, 398e1-2.

Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013 Apr;45(4):353-61, 361e1-2.

Precht JC, Schroth W, Klein K, Brauch H et al. The letrozole phase 1 metabolite carbinol as a novel probe drug for UGT2B7 Drug Metab Dispos. 2013 Nov;41(11):1906-13.

Hoppe R, Achinger-Kawecka J, Winter S et al. Increased expression of miR-126 and miR-10a predict prolonged relapse-free time of primary oestrogen receptor-positive breast cancer following tamoxifen treatment. Eur J Cancer. 2013 Nov;49(17):3598-608.

Justenhoven C, Pentimalli D, Rabstein S, et al. CYP2B6*6 is associated with increased breast cancer risk. Int J Cancer. 2013 Jul 3. doi: 10.1002/ijc.28356. [Epub ahead of print]

Justenhoven C, Obazee O, Winter S, et al. The UGT1A6_19_GG genotype is a breast cancer risk factor. Front Genet. 2013 Jun 11;4:104. 2013 Jun 11;4:104.

French JD, Ghoussaini M, Edwards et al. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. Am J Hum Genet. 2013 Apr 4;92(4):489-503.

Bojesen SE, Pooley KA, Johnatty SE, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013 Apr;45(4):371-84, 384e1-2. doi: 10.1038/ng.2566.

Obazee O, Justenhoven C, Winter S, et al. Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant. Breast Cancer Res Treat. 2013 Apr;138(2):543-8.

Justenhoven C, Obazee O, Winter S, et al. The Postmenopausal Hormone Replacement Therapy-Related Breast Cancer Risk is Decreased in Women Carrying the CYP2C19*17 Variant. Breast Cancer Res Treat. 2012 Jan;131(1):347-50.

Mürdter TE, Kerb R, Turpeinen et al. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet 2012 Mar 1;21(5):1145-54.

Precht JC, Ganchev B, Heinkele G et al. Simultaneous quantitative analysis of letrozole, its carbinol metabolite, and carbinol glucuronide in human plasma by LC-MS/MS. Anal Bioanal Chem. 2012 Apr;403(1):301-8.

Stevens KN, Fredericksen Z, Vachon CM, et al. 19p13.1 is a triple negative-specific breast cancer susceptibility locus. Cancer Res. 2012 Apr 1;72(7):1795-803.

Ghoussaini M, Fletcher O, Michailidou K, et al. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet. 2012 Jan 22;44(3):312-8.

Mürdter TE, Kerb R, Turpeinen M,et al. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet. 2012 Mar 1;21(5):1145-54.

Brauch HB, Schroth W, Ingle JN, et al. CYP2D6 and tamoxifen: awaiting the denouement. J Clin Oncol. 2011 Dec 1;29(34):4589-90.

Justenhoven C, Obazee O, Winter S et al. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant. Breast Cancer Res Treat. 2012 Jan;131(1):347-50.

Haiman CA, Chen GK, Vachon CM et al. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet. 2011 Oct 30;43(12):1210-4.

Figueroa JD, Garcia-Closas M, Humphreys M, et al. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium. Hum Mol Genet. 2011 Dec 1;20(23):4693-706.

Stevens KN, Vachon CM, Lee AM et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res. 2011 Oct 1;71(19):6240-9

Filipits M, Rudas M, Jakesz R et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011 Sep 15;17(18):6012-20.

Crooke PS, Justenhoven C, Brauch Het al. Estrogen metabolism and exposure in a genotypic-phenotypic model for breast cancer risk prediction. Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1502-15.

Broeks A, Schmidt MK, Sherman ME et al. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium. Hum Mol Genet. 2011 Aug 15;20(16):3289-303.

Mürdter TE, Schroth W, Bacchus-Gerybadze Let al. Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin Pharmacol Ther. 2011 May;89(5):708-17.

Yang XR, Chang-Claude J, Goode EL et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011 Feb 2;103(3):250-63.

Antoniou AC, Wang X, Fredericksen ZS et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet. 2010 Oct;42(10):885-92.

Konduri SD, Medisetty R, Liu W et al. Mechanisms of estrogen receptor antagonism toward p53 and its implications in breast cancer therapeutic response and stem cell regulation. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15081-6.

Schroth W, Hamann U, Fasching PA et al. CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Clin Cancer Res. 2010 Sep 1;16(17):4468-77.

Schroth W, Goetz MP, Hamann U, et al. Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Breast Cancer Treated With Tamoxifen. Journal of the American Medical Association 2009 Oct 7;302(13):1429-36.

Rokavec M, Schroth W, Amaral SM et al. A Polymorphism in the TC21 Promoter Associates with an unfavorable tamoxifen treatment outcome in Breast Cancer. Cancer Research 2008 Dec 1;68(23):9799-808.

Amaral S, Schroth W, Kugler S et al. The Promoter C Specific ERa Isoform is Associated with Tamoxifen Outcome in Breast Cancer. Breast Cancer Research and Treatment 2009 Nov;118(2):323-31.

Kaipparettu BA, Malik S, Konduri SD et al. Estrogen-mediated Down-regulation of CD24 in Breast Cancer Cells. International Journal of Cancer 2008 Jul 1;123(1):66-72.

Schroth W, Antoniadou L, Fritz P et al. Breast Cancer Treatment Outcome with Adjuvant Tamoxifen in Relation to Patient CYP2D6 and CYP2C19 Genotypes. Journal of Clinical Oncology 2007 Nov 20;25(33):5187-93.

Jaremko M, Justenhoven C, Schroth W, et al. A Polymorphism of the DNA Repair enzyme XRCC1 is associated with treatment prediction in anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of patients with primary invasive breast cancer. Pharmacogenetics and Genomics 2007 Jul;17(7):529-38.

Jaremko M, Justenhoven C, Abraham BK et al. MALDI-TOF MS and TaqMan assisted SNP genotyping of DNA isolated from formalin-fixed and paraffin embedded tissues (FFPET). Human Mutation 2005 Mar;25(3):232-8.

Abraham BK, Fritz P, McClellan M et al. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clinical Cancer Research 2005 Feb 1;11(3):1154-9.

Reviews

Schwab M, Schaeffeler1 E, Zanger UM et al. Pharmacogenomics: hype or hope ? Dtsch Med Wochenschr. 2011; 136(10): 461-467.

Brauch H, Mürdter TE, Eichelbaum M, et al. Pharmacogenomics of Tamoxifen Therapy Clinical Chemistry 2009 Oct;55(10):1770-82.

Brauch H and Jordan VC Targeting of Tamoxifen to Enhance Antitumour Action for the Treatment and Prevention of Breast Cancer: the "Personalised" Approach? European Journal of Cancer 2009 Sep;45(13):2274-83.

Brauch H, Schroth W, Eichelbaum M et al. Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Cancer. Breast Care 2008;3(1):43-50

Breast Cancer Susceptibility

The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer. Postmenopausal Estrogen Monotherapy Associated Breast Cancer Risk is Modified by CYP17A1_-34_T>C Polymorphism Breast Cancer Research and Treatment 2010, 120:737-744.

The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk associated with menopausal hormone therapy International Journal of Cancer 2010, 126:2935-46.

Wang X, Fredericksen ZS, Vierkant RA, Kosel ML, Pankratz VS, Cerhan JR, Justenhoven C, Brauch H, The GENICA Consortium, Olson JE, Couch FJ: Association of Genetic Variation in Mitotic Kinases with Breast Cancer Risk. Breast Cancer Research Treatment 2010; 119:453-462

The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Polymorphisms in the BRCA1 and ABCB1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women Breast Cancer Research and Treatment 2010, 120: 727-736, Epub 2009 Aug 12

MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women The Breast Cancer Res Treat 2009 May 8. [Epub ahead of print]

Milne et al. Risk of estrogen receptor positive and negative breast cancer and SNP rs13387042 on 2q35. Journal of the National Cancer Institute 101: 1012-1018, 2009 Epub 2009 Jun 30

Ahmed et al. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet. 2009 May;41(5):585-90. Epub 2009 Mar 29.

Justenhoven et al. The CYP1B1_1358_GG Genotype is Associated with Estrogen Receptor-Negative Breast Cancer. Breast Cancer Research and Treatment 2008; 111:171-177

Justenhoven et al., Breast Cancer: A Candidate Gene Approach across the Estrogen Metabolic Pathway Breast Cancer Research and Treatment 108: 137-149, 2008 [Epub ahead of print 2007 Jun 23, 2007]

Rokavec et al. A Novel Polymorphism in the Promoter Region of ERBB4 is Associated with Breast and Colorectal Cancer Risk Clinical Cancer Research 13:7506-7514, 2007

Easton et al. Genome-wide association study identifies breast cancer susceptibility loci Nature 447: 1087-1093, 2007 [Epub ahead of print]

Cox et al. A common coding variant in CASP8 is associated with breast cancer risk. Nature Genetics 39:352-358, 2007