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Breast cancer is the most frequent female cancer with more than 1.5 million newly diagnosed cases and more than 350.000 women dying from the disease each year worldwide. This is attributed to the lack of knowledge on how to maximize the efficacy of drug treatment and genetic risk factors. My research employs strategies that might help to cut down the burden of breast cancer by finding concepts that will improve treatment outcomes of endocrine therapy with tamoxifen and aromatase inhibitors.  We employ large patient collections (case-control and treatment cohorts) for the identification of susceptibility genes and treatment predictors by candidate gene, whole genome and epigenetic approaches. Candidates are further explored in mechanistic studies to establish biological evidence. Our translational research involves interdisciplinary collaborations among scientists with medical, epidemiological, molecular biology, pharmacology, and statistical expertise for the evaluation of clinical and complex omics data sets. The overall goal is to provide the knowledge and diagnostic tools as well as novel targets for the future exploration and implementation of personalized treatment schemes. Examples are:  (1) Tamoxifen: our pharmacogenomic approach identified cytochrome P450 (CYP) 2D6 as the limiting factor in the formation of endoxifen, an active metabolite critical for favorable outcome. Thus, supplementation of standard tamoxifen with endoxifen holds promise to overcome tamoxifen treatment failure in patients with compromised CY2D6 activity. The translational potential of this novel concept is currently being tested within a phase II trial (TAMENDOX) at the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology in collaboration with M. Schwab and T. Mürdter. (2) Overcoming endocrine resistance, which develops under long-term estrogen deprivation therapy, requires a better understanding of the underlying biological processes that result in the reprogramming of residual cancer cells towards becoming sensitive to estrogen-induced apoptosis. The latter is a proven concept in models and has been observed in patients, thus providing an intriguing novel treatment concept for patients who completed long-term endocrine treatment. In collaboration with the Jordan Laboratory at MD Anderson my group established a comprehensive miRNAome database of endocrine resistance models and identified key miRNAs and their regulatory pathways as well as potentially relevant miRNA-mRNA interactions that currently serve as a basis for the identification of novel targets for the amplification of the apoptotic trigger and biomarkers for the prediction of a recurrence risk. (3) At the molecular risk factor level my research team within a German collaborative effort established the Gene-Environment Interaction and Breast Cancer in Germany (GENICA) project, a population-based breast cancer case-control study that participates in the global efforts of the Breast Cancer Association Consortium (BCAC) towards the discovery of novel breast cancer susceptibility loci. Over the past decade more than 100 novel breast cancer susceptibility loci have been identified which provide a better understanding of the complex heritability of breast cancer.

Research Topics

· Breast cancer susceptibility

· Breast cancer pharmacogenomics

· Target identification to overcome endocrine resistance

· Biomarker development for breast cancer management

· Novel drug concepts for the improvement of endocrine therapy