When cancer runs in the family

5% to 10% of all breast cancers are monogenic in origin. In other words, there is a mutation of the genes BRCA1, BRCA2 or other high-risk genes. In this edition of Deutsches Ärzteblatt International (Dtsch Arztebl Int 2011; 108(19): 323 30), Alfons Meindl of the Klinikum rechts der Isar (Munich) and coauthors report on new insights into the pathogenesis and treatment of hereditary breast and ovarian cancer and newly-discovered risk genes.

Meindl et al. evaluated data including those derived from the work of the German Consortium for Hereditary Breast and Ovarian Cancer. It was shown that if BRCA1 or BRCA2 is mutated, there is a breast cancer risk of up to 85% and an ovarian cancer risk of up to 50%. Another predisposing gene for breast and ovarian cancer is RAD51C. Like BRCA1 and BRCA2, it plays a central role in DNA repair and is mutated in approximately 1.5% to 4% of all families predisposed towards breast and ovarian cancer.

When there is evidence of a high-risk gene mutation, the authors recommend intensive risk-adjusted screening. Risk can be reduced by prophylactic bilateral removal of the breasts and ovaries. In the future, drug-based approaches to risk reduction may also be possible.

In Germany, breast cancer is the most common malignant disease in women and ovarian cancer the gynecological tumor with the highest mortality rate. There may be a hereditary cancer burden even if only two or more women, or one young woman, in a family develop the disease.

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Contact: Prof. Dr. Alfons Meindl
[email protected]
Deutsches Aerzteblatt International

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Hereditary Breast and Ovarian Cancer

New Genes, New Treatments, New Concepts

Background: Every year, 60 000 women in Germany are found to have breast cancer, and 9000 to have ovarian cancer. Familial clustering of carcinoma is seen in about 20% of cases.

Methods: We selectively review relevant articles published up to December 2010 that were retrieved by a search in PubMed, and we also discuss findings from the experience of the German Consortium for Hereditary Breast and Ovarian Cancer.

Results: High risk is conferred by the highly penetrant BRCA1 and BRCA2 genes as well as by other genes such as RAD51C. Genes for breast cancer that were originally designated as moderately penetrant display higher penetrance than previously thought in families with a hereditary predisposition. The role these genes play in DNA repair is thought to explain why tumors associated with them are sensitive to platin derivatives and PARP inhibitors. In carriers of BRCA1 and BRCA2, prophylactic bilateral mastectomy and adnexectomy significantly lowers the incidence of breast and ovarian cancer. Moreover, prophylactic adnexectomy also lowers the breast-and-ovarian-cancer-specific mortality, as well as the overall mortality. If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.