Breast Cancer Susceptibility and Pharmacogenomics
Breast cancer is the most frequent female cancer with more than one million newly diagnosed cases and more than 350.000 women dying from the disease each year worldwide. This is mainly attributed to the lack of known risk factors as well as lack of efficient and non-toxic anti-cancer drugs. My research employs strategies that might help to cut down the incidence of breast cancer by way of molecular epidemiological studies and to improve treatment outcomes of available therapies by way of pharmacogenomic approaches. My research team employs large patient collections (case-control and treatment cohorts) for the identification of susceptibility genes and treatment predictors by candidate gene, whole genome as well as epigenetic approaches. Candidates are further explored in mechanistic studies to establish biological evidence. This translational research involves a high degree of interdisciplinary collaboration among scientists with medical, epidemiological, laboratory and statistical expertises for the complex evaluation of clinical and laboratory data obtained via high-throughput molecular analyses. The overall goal is to provide the knowledge and diagnostic tools for future exploration and implementation of personalized treatment schemes.
Major projects
- Candidate and genome wide search for breast cancer susceptibility genes
- Genotype – phenotype correlations for the description of breast cancer subtypes
- Tamoxifen pharmacogenomics and translation
- Estrogen receptor regulation
- Pharmacogenomics of anti cancer drugs
- Epigenetic approaches for the identification of novel treatment predictors and drug targets
- PhD Curriculum “Fighting Drug Failure”
Prof. Dr. Hiltrud B. Brauch
phone: ++49-711-8101 3705
Selected References
Original Articles
Reviews
- 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 126:2935-46, 2010
- 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 302:1429-1436, 2009
- Ahmed S, Thomas G, Ghoussaini M, et al. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nature Genetics. 2009 May;41(5):585-90. Epub 2009 Mar 29.
- 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 2008 Nov [Epub ahead of print] 118:323-331, 2009
- 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 68:9799-808, 2008
- Abraham Kaipparettu B, Zubairy S, et al. Estrogen-mediated Down-regulation of CD24 in Breast Cancer Cells. International Journal of Cancer 2008; 123:66-72
- 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 33:5187-5193, 2007
- Jaremko M, Justenhoven C, Schroth W, et al. A Polymorphism of the DNA Repair enzyme XRCC1 is associated with treatment prediction in aqnthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of patients with primary invasive breast cancer. Pharmacogenetics and Genomics 17:529-538, 2007
- Easton DF, Pooley KA, Dunning AM, et al. Genome-wide association study identifies breast cancer susceptibility loci. Nature 447: 1087-1093, 2007 [Epub ahead of print]
- Cox A, Dunning AM, Garcia-Closas M, et al. A common coding variant in CASP8 is associated with breast cancer risk. Nature Genetics 39:352-358, 2007
- 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 25:232-238, 2005
- 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 11:1154-59, 2005
Reviews
- Brauch H, Mürdter TE, Eichelbaum M, Schwab M Pharmacogenomics of Tamoxifen Therapy. Clinical Chemistry 2009 Jul 2 [Epub ahead of print ] 55:1770-1782, 2009
- 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 45: 2274-2283, 2009
- Brauch H, Schroth W, Eichelbaum M, Schwab M, and Harbeck N in cooperation with the AGO TRAFO Commission Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Care 3: 43-50, 2009
Major Networks and Collaborations
- Breast Cancer Association Consortium (BCAC)
- International Tamoxifen Pharmacogenomics Consortium (Member of Steering Committee)
- The Interdisciplinary Study Group on Gene ENvironment Interactions and Breast CAncer in Germany (GENICA) (Scientific Coordinator)
- The MARIE-GENICA Consortium for the identification of constitutional factors predictive for the risk to develop breast cancer following hormone replacement therapy (Head Steering Committee)
- Scientific Advisory Board of the VHL Family Alliance Germany (Verein für von der von Hippel-Lindau (VHL) Erkrankung betroffene Familien e.V.
- Marie Curie Initial Training Network (ITN) “Fighting Drug Failure: Priorities and Standards in Pharmacogenomics Research: Opportunities for a Safer and More Efficient Pharmacotherapy (Coordinator)
Curriculum Vitae Hiltrud Beatrix Brauch, PhD
Affiliation
Deputy Head Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Head Breast Cancer Susceptibility and Pharmacogenomics
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Auerbachstrasse 112
70376 Stuttgart, Germany
phone: ++49-711-8101 3705
fax: ++49-711-859295
email: hiltrud.brauch@ikp-stuttgart.de
Head Breast Cancer Susceptibility and Pharmacogenomics
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Auerbachstrasse 112
70376 Stuttgart, Germany
phone: ++49-711-8101 3705
fax: ++49-711-859295
email: hiltrud.brauch@ikp-stuttgart.de
Education and Professional Career
| 1975-1981 | Study of Chemistry (Diploma), University Fridericiana Karlsruhe (TH), Germany |
| 1981-1985 | Dissertation: Regulation of Complement Lysis by a Membrane Glycoprotein (Glycophorin A), Institute of Immunology and Serology and Institute of Physical Chemistry, Ruprecht-Karls-University Heidelberg, Germany |
| 1985-1988 |
Fogarty International Visiting Fellowship, Program of Collaborative Research Experience in the United States, The National Institutes of Health (NIH), USA 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 |
| 1988-1990 | Scientist, LIB, PRI-Inc. NCI-FCRDC, Frederick, MD, USA |
| 1990-1992 | Scientist, German Cancer Research Center (DKFZ), Germany |
| 1992-1996 |
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 Research Laboratory and Gynecological Diagnostics, Womens Hospital Eppendorf, University of Hamburg, Germany; Venia Legendi in Molecular Biology |
| 1999-present | 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 University Tübingen |
| 2006 | Extraordinary Professorship at the University Tübingen Medical School |
| since 2008 | Deputy Head of Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Head Breast Cancer Susceptibility and Pharmacogenomics |
Professional Memberships
1996-present: American Association of Cancer Research (AACR)
AACR-Molecular Epidemiology Group (MEG)
AACR-Women in Cancer Research (WICR)
1996-present: American Society of Human Genetics (ASHG)
2000-present: Gesellschaft für Biochemie und Molekularbiologie (GBM)
2007-present: Verein für von der von Hippel-Lindau (VHL) Erkrankung betroffene Familien e.V. (Board of Scientists of the VHL Family Alliance Germany)
AACR-Molecular Epidemiology Group (MEG)
AACR-Women in Cancer Research (WICR)
1996-present: American Society of Human Genetics (ASHG)
2000-present: Gesellschaft für Biochemie und Molekularbiologie (GBM)
2007-present: Verein für von der von Hippel-Lindau (VHL) Erkrankung betroffene Familien e.V. (Board of Scientists of the VHL Family Alliance Germany)
Scientific Journal Editorial Board Memberships
2006-present: Pharmacogenetics and Genomics
Member of Organization Committees for Scientific Conferences
Cold Spring Harbor Laboratory Conference: Pharmacogenomics & Personalized Medicine (since 2009)
New Developments in the Endocrine Treatment of Breast Cancer, IKP Stuttgart, February 5, 2009
New Developments in the Endocrine Treatment of Breast Cancer, IKP Stuttgart, February 5, 2009