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Geburtshilfe Frauenheilkd 2013; 73(12): 1228-1235
DOI: 10.1055/s-0033-1360178
DGGG Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Breast Cancer Risk – From Genetics to Molecular Understanding of Pathogenesis

Mammakarzinomrisiko – Genetik und molekulare Mechanismen der Pathogenese
P. A. Fasching
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
A. B. Ekici
2   Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
D. L. Wachter
3   Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
A. Hein
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
C. M. Bayer
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
L. Häberle
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
C. R. Loehberg
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
M. Schneider
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
S. M. Jud
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
K. Heusinger
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
M. Rübner
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
C. Rauh
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
M. R. Bani
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
M. P. Lux
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
,
R. Schulz-Wendtland
4   Institute of Diagnostic Radiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
A. Hartmann
3   Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
M. W. Beckmann
1   Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

received 01 December 2013
revised 01 December 2013

accepted 02 December 2013

Publication Date:
20 December 2013 (online)

Also available at
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Abstract

Several advancements over the last decade have triggered the developments in the field of breast cancer risk research. One of them is the availability of the human genome sequence along with cheap genotyping possibilities. Another is the globalization of research, which has led to the growth of research collaboration into large international consortia that facilitate the pooling of clinical and genotype data of hundreds of thousands of patients and healthy control individuals. This review concerns with the recent developments in breast cancer risk research and focuses on the discovery of new genetic breast cancer risk factors and their meaning in the context of established non-genetic risk factors. Finally the clinical application is highly dependent on the accuracy of breast cancer risk prediction models, not only for all breast cancer patients, but also for molecular subtypes, preferably for those which are associated with an unfavorable prognosis. Recently risk prediction incorporates all possible risk factors, which include epidemiological risk factors, mammographic density and genetic risk factors.

Zusammenfassung

In den letzten Jahren sind, begünstigt durch einige Fortschritte, neue Entdeckungen auf dem Gebiet der Erforschung des Brustkrebserkrankungsrisikos gemacht worden. Zum einen stehen nach der Veröffentlichung des Referenz-Genoms preiswerte Genotypisierungsmethoden zur Verfügung und zum anderen haben sich Forschungskooperationen im Rahmen der Globalisierung in riesige Konsortien weiterentwickelt. In diesen Konsortien stehen genetische und nicht genetische Informationen von mehreren hunderttausend Brustkrebspatientinnen und gesunden Kontrollpersonen zur Verfügung. Diese Übersichtsarbeit stellt die jüngsten Entwicklungen und Entdeckungen sowohl für genetische Risikofaktoren als auch für deren Interaktion mit etablierten klinischen und epidemiologischen Risikofaktoren dar. Da die klinische Anwendung von der Genauigkeit einer Risikoprädiktion abhängig ist, versuchen Risikoprädiktionsmodelle so viele Risikofaktoren wie möglich in die Prädiktion des Erkrankungsrisikos mit einzubeziehen. Die Risikoprädiktion sollte sich nicht nur auf alle Frauen und Brustkrebspatientinnen beziehen, sondern, wenn möglich, auch das Risiko für molekulare Subtypen berücksichtigen. Insbesondere die Risikoprädiktion für molekulare Subtypen, wie das triple-negative Mammakarzinom, wären von besonderer Bedeutung.

Key words

breast cancer risk - genetic risk factors - prediction models - gene–environment interaction - BRCA

Schlüsselwörter

Mammakarzinom - Risikofaktoren - Risikoprädiktion - Gen-Umwelt-Interaktion
 

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