The AKT1 (E17K) mutation is rare and occurs in colon, ovarian, lung, and especially breast cancer where its frequency ranges between 1.4% and 8.2%. It's precise role in cancer development and progression in clinical context is still unknown. To increase our understanding of the AKT1 (E17K) mutation in breast cancer we analyzed more than 600 tumor samples from breast cancer patients (UICC I - IV, including untreated and neoadjuvantly treated patients) which were provided by the non-profit organization PATH (Patients’ Tumor Bank of Hope, Germany). Extensive clinical data with a median follow-up time of 4.8 years to record disease progression were available for 95% of the patients included in this study. The AKT1 (E17K) mutation was detected in ∼6% of samples in the analyzed cohort using the BEAMing technology. Correlation with clinical parameters showed that the prevalence of the AKT1 (E17K) mutation was statistically independent of age or post-/pre-menopausal stage and was comparable between HER-2 positive and negative patients. In addition, FOUNDATION ONE® targeted exome Next Generation Sequencing (NGS) analysis of some of the tumor samples was done to demonstrate the fingerprint of individual tumors in correlation with the AKT1 (E17K) mutation. NGS and BEAMing technology had a ∼98% concordance for AKT1 (E17K) mutated and non-mutated samples. In 12 out of 36 AKT1 (E17K) mutated samples no additional somatic mutations (SNVs, indels) described to drive cancer development were detected. Moreover, neither amplification nor deletion of tested genes known to be recurrently amplified or deleted in cancer were found in 10 out of these 12 samples. This supports the hypothesis that AKT1 (E17K) can be a driver mutation. However, in all of these samples mutations with yet unannotated function in additional oncogenes were detected. It remains open whether these aberrations impact the role of AKT1 (E17K) as a driver mutation in tumor growth. Analyses of patient cohort data from large databases, as demonstrated here, holds promise for discovering the role of rare somatic mutations in known oncogenes (such as AKT1 (E17K)) in the development of breast cancer. Citation Format: Marion Rudolph, Tobias Anzeneder, Matthias Ocker, Eleni Lagkadinou, Oliver Politz, Martin Michels, Anke Schulz, Georg Beckmann, Michael Teufel, Henrik Seidel, Richie Soong, Heinz Bodenmüller, Ulla Ohlms, Khusru Asadullah, Joachim Reischl. AKT1 (E17K) mutation: coexistence with oncogenic alterations, prevalence, and correlation to clinical parameter in a large series of breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 569. doi:10.1158/1538-7445.AM2014-569

Introduction: Since 2002, PATH Foundation has kept a biobank collecting high-quality fresh frozen breast cancer specimens adhering to uniform SOPs at seven certified breast cancer centres in Germany. Research groups from academia and industry can obtain samples after application and review. PATH Biobank is a not-for-profit organisation and asks for a cost recovery fee in exchange for sample allocation to sustainably finance the expenses it incurs. Material and methods: The PATH Biobank consists of a centralized database and a decentralized bio repository. The samples are collected and stored at seven institutes for pathology at certified German breast cancer centres. Tumour tissue, along with normal (benign) adjacent tissue and blood serum aliquots are processed, labelled and stored according to uniform SOPs. Informed consent to biobanking and the use of the samples and data for research is obtained from the donors individually during pre-operation discussions. Results: Since 2004, more than 8,600 breast cancer patients have given their informed consent to the storage and analysis of their tissue and blood serum for research purposes. Breast cancer tissue samples from 59% of donors could be stored due to size of the surgically removed tissue specimen. In addition, normal adjacent tissue is available from 62% of donors and blood serum aliquots can be derived from 92% of patients. Using the annotating data, 96% of donors can be classified into the intrinsic molecular breast cancer subtypes in accordance with the St. Gallen Criteria. In 2008, PATH Biobank started to support research groups by providing breast cancer samples and data as well as informing the public about the projects on-line. In 2015 three co operations resulted in scientific publications. One landmark collaborations started in 2012 and has been studying the frequency and background of defined mutations in breast cancer. A number of 701 tissue samples have been used for this study. All samples were subject to quality testing, only 11% failed due to less than 5% tumour content. Tumour content depended on clinical conditions and staging (ranging from 34% failure in samples derived from neo adjuvantly treated patients to 2% in cases with staging UICC IV). Additional results concerning the quality of samples from PATH Biobank will be presented. Conclusions: For breast cancer research and biomarker studies, PATH Biobank can be a valuable resource. Citation Format: Tobias Anzeneder, Ulla Ohlms, Heinz Bodenmüller. Real-life example of biobanking: results of the PATH Biobank. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 398.

No abstract

Purpose: Breast Cancer Patients established PATH in 2002 to collect tumor sam-ples, blood samples and data at high ethical standards and under uniform SOPs. Since 2004 more then 4500 women and men in Germany gave their informed consent for the collection. In addition, PATH has successfully started to collect follow-up data from all patients, covering both disease and therapy process. Design: Specimen (tumor, normal tissue, blood serum) are stored in liquid nitrogen tanks (fresh frozen quality) operated by pathologists at seven certified breast cancer centers in Germany. To provide a benefit for the donors, the first aliquot is stored exclusively for the patient. The rest of the material is donated to research purposes. Processing, handling and labelling of the samples is defined in rigid SOPs, accompanied by monitoring. Data regarding clinical findings, tumor-biology and sample processing are collected and centrally managed. In order to annotate the samples follow up started in early 2009. As a patient driven, non-profit organization PATH has a special reliability. Thus, the Foundation is given the right to establish direct contact with any patient that has given informed con-sent. This approach was confirmed by ethics committee, the Bavarian Commission of Data Protection and a university professor of medical law. In order to get the follow-up data, PATH contacts the patient by letter. A structured phone call follows, carried out by female medical students, who are specially trained. The patient is asked to provide details on their individual course of disease. Additionally they are asked about their compliance with therapy. Procedure, data volume and data quality are specified and standardized. If patients could not be reached by call they are asked to complete an additionally mailed questionnaire. As the last source for data PATH will try to get data from tumor registers. In case of re-currence the data obtained from the patients is validated by check-ups with medical reports from the practitioners. Results: By May 2010 more than 4500 patients gave informed consent. 4042 cases have been documented in their entirety in the data base. 75% have stored a patient's tumor specimen and 61% a research tumor sample in the bio bank. As many patients have multiple samples there is a total of 4080 tumor specimen, 9029 blood serum and 4075 normal tissue aliquots for research purposes. 2253 cases were contacted for follow up, 1491 (66,2%) patients were interviewed by phone and 142 (6,3%) women returned the questionnaire. In 72,5% of the con-tacted cases follow-up data is available. The mean age of all patients who do-nated their tumor specimen is 60,3 years. 78,9% of the tumors are ER-positive, 11,4% triple negative. The data includes 20 cases of recurrence and 61 cases of metastases. Conclusion: Within 16 months PATH contacted 40% of all patients included in the bio bank and gained follow up data. Thus PATH will provide a great variety and quantity of fresh frozen tissue and blood samples with excellent quality and a mean follow up of 5 years in less than 12 months. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-13-01.

No abstract