Breast Cancer Risk – Genes, Environment and Clinics

Abstract

The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case–control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patientʼs breast cancer risk.

Zusammenfassung

Das Wissen über Brustkrebsrisikofaktoren hat in den letzten 10 Jahren deutlich zugenommen. Insbesondere die Bedeutung von niedrigpenetranten Risikogenen konnte besser verstanden werden. Zusätzlich werden erste Schritte unternommen, um das Zusammenspiel zwischen Umweltfaktoren und genetischen Faktoren besser zu verstehen. Einige genomweite Assoziationsstudien von Fall-Kontroll-Studien und groß angelegte Validierungsstudien konnten mehr als ein Dutzend validierte Single Nucleotid Polymorphismen (SNPs) als genetische Risikofaktoren etablieren. Dabei handelt es sich um Veränderungen in Genen, von denen teilweise bekannt war, dass sie bei der Pathogenese des Mammakarzinoms eine Rolle spielen. Andere dieser Gene waren bislang noch nicht mit der Biologie des Mammakarzinoms in Verbindung gebracht worden. Auch konnten SNPs identifiziert werden, die das Lebenszeitrisiko von BRCA-Mutationsträgern modifizieren können. In Bezug auf nicht genetische Risikofaktoren hat das Wissen um die Hormonersatztherapie (HRT) in den letzten 10 Jahren deutlich zugenommen, sodass eine bessere Nutzen-Risiko-Bewertung vorgenommen werden konnte. Die mammografische Dichte hat sich als wichtiger und akzeptierter Risikofaktor etabliert. Lifestyle und Ernährung werden nach wie vor mit großem Interesse als Risikofaktoren für das Mammakarzinom untersucht. Einige Studien konnten auch auf diesem Gebiet das Wissen erweitern. Mehr als 10 Jahre nach der Publikation der ersten Chemopräventionsstudien gibt es nunmehr nicht nur zur Substanz Tamoxifen Ergebnisse. Auch zu Raloxifen und Aromatasehemmern gibt es Studien, die deren protektive Wirkung nachgewiesen haben. Schließlich wurde in den meisten westlichen Industrieländern das Mammografiescreening als Früherkennung etabliert und bereits jetzt werden Überlegungen unternommen, wie man durch die Integration von individualiserter Risikoprädiktion die Früherkennung verbessern könnte.

Key words

BRCA (breast cancer antigen) - breast - breast feeding - CAM (Complementary and Alternative medicine) - cancer registry - estrogen receptor

Schlüsselwörter

BRCA - Mamma - Mammakarzinom - mammografische Dichte - Plazenta - Polymorphismus

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