Double heterozygosity for disease-causing BRCA1 and BRCA2 mutations is a very rare condition in most populations. Here we describe genetic and clinical data of eight female double heterozygotes (DH) for BRCA1 and BRCA2 mutations found in a cohort of 8162 German breast/ovarian cancer families and compare it with the data of their single heterozygous relatives and of the index patients of the German Consortium for Hereditary Breast and Ovarian Cancer. Furthermore, we analyze the phenotypic features of these patients with respect to age at onset of first cancer, first breast/ovarian cancer and the number of disease manifestations and compare them to that of published Caucasian female DHs and their single heterozygous female relatives. German DHs were not significantly younger at diagnosis of first breast cancer than the single heterozygous index patients of the German Consortium. However, if the data of our study were pooled with that of the literature, DHs were substantially younger at onset of first cancer (mean age 40.4 years, 95 % CI = 36.6-44.1) than their single heterozygous female relatives (mean age 51.9 years, 95 % CI = 46.8-57.0). The two groups also differed concerning the onset of first breast cancer (mean age 40.6 years, 95 % CI = 36.6-44.5 vs. 52.6, 95 % CI = 47.5-57.6). In addition, DHs had a more severe disease than their female relatives carrying a single BRCA mutation (1.4 vs. 0.6 manifestations per person). In contrast to Ashkenazi Jewish females, Caucasian DH females might develop breast cancer at an earlier age and have a more severe disease than single heterozygous BRCA mutation carriers. Therefore, DHs may benefit from more intensive surveillance programs/follow-up care and prophylactic surgery.

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Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2 and nine additional can-cer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and methods: In 1600 women with sTNBC (median age at diagnosis 41 years, range 19-78 years) we investigated the association between age at diagnosis and PV occur-rence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n=170 [10.6%]; BRCA2: n=46 [2.9%], other: n=44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n=194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95%CI 1.21-1.65; p <0.001). The PV prevalence pre-dicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still wide confi-dence interval (7.6-16-6), we recommend the implementation within the framework of a knowledge-generating care concept.

Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.

In January 2007, the ‘AGO Kommission Mamma’ for the 5th time updated the ‘AGO Recommendations for the Diagnostic and Therapy of Breast Cancer’ that were established and published for the first time in 2002. The most important statements and modifications are described here. With regard to adjuvant therapy, the definition of the recommended regimens could be established more precisely. The increasing knowledge about the clinical value of sentinel lymph node excision is taken into consideration. For the pathological work-up, the needs and standards of additional markers and prognostic factors were better defined and adjusted to the guidelines of the German pathologists. The routine use of gene arrays for therapy decision is still rejected. Detailed recommendations were established for acute and long-term side effects of therapy. In the chapter ‘specific situations’, CUP (carcinoma of unknown primary) syndrome and phyllodes tumor were included. Taking into account the improved prognosis of breast cancer, specific advice for survivors and information about complementary therapy, hormone therapies, and contraception was prepared in detail. The treatment principles of metastastic disease have not changed substantially, thus pronouncing the significance of guiding therapy by defining the goal and estimating the therapeutic index for each situation.