In Germany, most breast cancer patients are treated in specialized breast cancer units (BCU), which are certified, and routinely monitored. Herein, we evaluate up-to-date oncological outcome of breast cancer (BC) molecular subtypes in routine clinical care of a specialized BCU. The study was a prospectively single-center cohort study of 4102 female cases with primary, unilateral, non-metastatic breast cancer treated between 01 January 2003 and 31 December 2012. The five routinely used molecular subtypes (Luminal A-like, Luminal B/HER2 negative-like, Luminal B/HER2 positive-like, HER2-type, Triple negative) were analyzed. The median follow-up time of the whole cohort was 55 months. We calculated estimates for local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and relative overall survival (ROS). Luminal A-like tumors were the most frequent (44.7 %) and showed the best outcome with LCR of 99.1 % (95 % CI 98.5; 99.7), OS of 95.1 % (95 % CI 93.7; 96.5), and ROS of 100.0 % (95 % CI 98.5; 101.5). Triple negative tumors (12.3 %) presented the poorest outcome with LCR of 89.6 % (95 % CI 85.8; 93.4), OS of 78.5 % (95 % CI 73.8; 83.3), and ROS of 80.1 % (95 % CI 73.8; 83.2). Patients with a favorable subtype can expect an OS above 95 % and an LCR of almost 100 % over 5 years. On the other hand the outcome of patients with HER2 and Triple negative subtypes remains poor, thus necessitating more intensified research and care.

Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3) are autosomal‐dominantly inherited, neurodegenerative diseases caused by CAG repeat expansions in the coding regions of the genes encoding ataxin‐2 and ataxin‐3, respectively. To provide a rationale for further functional experiments, we explored the protein architectures of ataxin‐2 and ataxin‐3. Using structure‐based multiple sequence alignments of homologous proteins, we investigated domains, sequence motifs, and interaction partners. Our analyses focused on presumably functional amino acids and the construction of tertiary structure models of the RNA‐binding Lsm domain of ataxin‐2 and the deubiquitinating Josephin domain of ataxin‐3. We also speculate about distant evolutionary relationships of ubiquitin‐binding UIM, GAT, UBA and CUE domains and helical ANTH and UBX domain extensions.

Over the last few years, circulating microRNAs (miRNAs) have emerged as promising novel and minimally invasive markers for various diseases, including cancer. We already showed that certain miRNAs are deregulated in the plasma of breast cancer patients when compared to healthy women. Herein we have further explored their potential to serve as breast cancer early detection markers in blood plasma. Circulating miR-127-3p, miR-376a and miR-652, selected as candidates from a miRNA array-based screening, were found to be associated with breast cancer for the first time (n = 417). Further we validated our previously reported circulating miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) in an independent cohort (n = 210) as elevated in the plasma of breast cancer patients compared to healthy women. We described, for the first time in breast cancer, an over-representation of deregulated miRNAs (miR-127-3p, miR-376a, miR-376c and miR-409-3p) originating from the chromosome 14q32 region. The inclusion of patients with benign breast tumors enabled the observation that miR-148b, miR-652 and miR-801 levels are even elevated in the plasma of women with benign tumors when compared to healthy controls. Furthermore, an analysis of samples stratified by cancer stage demonstrated that miR-127-3p, miR-148b, miR-409-3p, miR-652 and miR-801 can detect also stage I or stage II breast cancer thus making them attractive candidates for early detection. Finally, ROC curve analysis showed that a panel of these seven circulating miRNAs has substantial diagnostic potential with an AUC of 0.81 for the detection of benign and malignant breast tumors, which further increased to 0.86 in younger women (up to 50 years of age).

Introduction: While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations. Methods: A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status. Results: The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families. Conclusions: Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy.