Health benefits of the Mediterranean Diet (MD) have been shown in different at-risk populations. A German translation of the Mediterranean Diet Adherence Screener (MEDAS) from the PREvención con DIeta MEDiterránea (PREDIMED) consortium was used in the LIBRE study, investigating effects of lifestyle-intervention on women with BRCA1/2 mutations. The purpose of the present study is to validate the MEDAS German version. LIBRE is a multicentre (three university hospitals during this pilot phase), unblinded, randomized, controlled clinical trial. Women with a BRCA1/2 mutation of age 18 or over who provided written consent were eligible for the trial. As part of the assessment, all were given a full-length Food Frequency Questionnaire (FFQ) and MEDAS at baseline and after 3 months. Data derived from FFQ was compared to MEDAS in order to evaluate agreement or concordance between the two questionnaires. Additionally, the association of dietary intake biomarkers in the blood (β-carotene, omega-3, omega-6 and omega-9 fatty acids and high-sensitivity C-reactive protein (hsCRP)) with some MEDAS items was analyzed using t-Tests and a multivariate regression. The participants of the LIBRE pilot study were 68 in total (33 Intervention, 35 Control). Only participants who completed both questionnaires were included in this analysis (baseline: 66, month three: 54). The concordance between these two questionnaires varied between the items (Intraclass correlation coefficient of 0.91 for pulses at the highest and −0.33 for sugar-sweetened drinks). Mean MEDAS scores (sum of all items) were 9% higher than their FFQ counter-parts at baseline and 15% after 3 months. Higher fish consumption (at least 3 portions) was associated with lower omega-6 fatty acid levels (p = 0.026) and higher omega-3 fatty acid levels (p = 0.037), both results being statistically significant. We conclude that the German MEDAS in its current version could be a useful tool in clinical trials and in practice to assess adherence to MD. ClinicalTrials.gov , registered on March 12, 2014, identifier: NCT02087592 . World Health Organization Trial Registration, registered on 3 August 2015, identifier: NCT02087592 .

There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years. Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.

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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.

PURPOSE: Rapidly expanding medical literature challenges oncologists seeking targeted cancer therapies. General-purpose large language models (LLMs) lack domain-specific knowledge, limiting their clinical utility. This study introduces the LLM system Medical Evidence Retrieval and Data Integration for Tailored Healthcare (MEREDITH), designed to support treatment recommendations in precision oncology. Built on Google's Gemini Pro LLM, MEREDITH uses retrieval-augmented generation and chain of thought . METHODS: We evaluated MEREDITH on 10 publicly available fictional oncology cases with iterative feedback from a molecular tumor board (MTB) at a major German cancer center. Initially limited to PubMed -indexed literature (draft system), MEREDITH was enhanced to incorporate clinical studies on drug response within the specific tumor type, trial databases, drug approval status, and oncologic guidelines. The MTB provided a benchmark with manually curated treatment recommendations and assessed the clinical relevance of LLM-generated options (qualitative assessment). We measured semantic cosine similarity between LLM suggestions and clinician responses (quantitative assessment). RESULTS: MEREDITH identified a broader range of treatment options (median 4) compared with MTB experts (median 2). These options included therapies on the basis of preclinical data and combination treatments, expanding the treatment possibilities for consideration by the MTB. This broader approach was achieved by incorporating a curated medical data set that contextualized molecular targetability. Mirroring the approach MTB experts use to evaluate MTB cases improved the LLM's ability to generate relevant suggestions. This is supported by high concordance between LLM suggestions and expert recommendations (94.7% for the enhanced system) and a significant increase in semantic similarity from the draft to the enhanced system (from 0.71 to 0.76, P = .01). CONCLUSION: Expert feedback and domain-specific data augment LLM performance. Future research should investigate responsible LLM integration into real-world clinical workflows.

Denaturing high performance liquid chromatography (DHPLC) is generating increasing interest in clinical genetics as a reliable tool for the analysis of genetic alterations. In the work presented here our intentions were to optimize primer design and DHPLC analysis conditions for a qualitative detection of BRCA1 and BRCA2 variations. The BRCA1 and BRAC2 genes display a high proportion of polymorphisms. Sequencing efforts geared towards the distinction of tumor-related mutations and benign variants still remain time-consuming and expensive. DHPLC elution profiles, however, permit the correlation of a characteristic chromatographic profile with a specific sequence alteration. In this study we evaluate the sensitivity of DHPLC for the identification of unique polymorphisms, which are frequent in the Caucasian population, in lieu of sequence analysis. The complete BRCA1 gene and parts of BRCA2 were examined. In the case of BRCA1, 431 out of 432 heterozygotes were identified correctly. In addition, 18 new profiles were identified which had not been detected previously in our studies and which represented new mutations or rare polymorphisms. For BRCA2, 135 out of 137 simple sequence variants were classified correctly. In addition, six new profiles were identified which represented new mutations or rare polymorphisms.