Guideline for designing microbiome studies in neoplastic diseases.

Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the oncobiome can support the progression of tumors, and the emerging therapeutic opportunities they present. The review highlights the inherent challenges and limitations faced in sampling and accurately characterizing oncobiome. Additionally, the review underscores the critical need for the standardization of microbial analysis techniques and the consistent reporting of microbiome data. We provide a suggested metadata set that should accompany microbiome datasets from oncological settings so that studies remain comparable and decipherable.

Beyond a decade: a comparative study of 15-year survival rates in screen-detected vs. symptomatic breast cancer patients in Hungary.

BACKGROUND: Breast cancer is the leading cancer in women globally. Despite decreasing mortality rates, largely due to early detection and modern treatment, the effectiveness of screening on long-term survival outcomes remains unclear. AIMS: This study evaluates the 15-year survival outcomes of a national breast cancer screening program initiated in Hungary in 2002. METHODS: Using a prospectively maintained patient database, the study included individuals from the first 6 years of the program who underwent surgery for histologically confirmed breast cancer and had available follow-up information. Patients were categorized based on the method of breast cancer detection into two groups: those diagnosed during or 2 years after the population-based screening exam (Group A), and those who self-detected or sought medical attention for symptoms (Group B). RESULTS: Of the 309 patients who underwent breast cancer surgery, 208 were screen-detected (Group A) and 101 were symptomatic (Group B). The 15-year overall survival was 75.0% for Group A and 76.2% for Group B (p = 0.927). The 15-year disease-specific survival was 85.6% and 81.2% (p = 0.249), respectively. A statistically not significant positive trend in disease-free survival was observed in Group A (81.7% vs. 75.2%; p = 0.144). CONCLUSIONS: The study underscores the importance of extended follow-up periods in evaluating the outcomes of breast cancer screening programs. While the screening program may not significantly enhance overall survival rates, it has demonstrated a reduction in the mastectomy rate and could potentially extend periods of disease-free survival. These findings contribute to the ongoing discourse about the long-term benefits of breast cancer screening programs.

Use of Diagnostic Imaging Modalities in Modern Screening, Diagnostics and Management of Breast Tumours 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

Breast radiologists and nuclear medicine specialists updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference in Kecskemét. A recommendation is hereby made that breast tumours should be screened, diagnosed and treated according to these guidelines. These professional guidelines include the latest technical developments and research findings, including the role of imaging methods in therapy and follow-up. It includes details on domestic development proposals and also addresses related areas (forensic medicine, media, regulations, reimbursement). The entire material has been agreed with the related medical disciplines.

[Radiology/Nuclear Medicine Group. Use of imaging methods in the current screening, diagnostics and treatment of breast cancer - Professional guidelines. 4th Breast Cancer Consensus Conference]. / A képalkotó vizsgálómódszerek alkalmazása az emlodaganatok korszeru szurésében, diagnosztikájában és ellátásában ­ Szakmai útmutató a IV. Emlorák Konszenzus Konferencia alapján.

Breast radiologists and nuclear medicine specialists have updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference. They suggest to adopt this actual protocol for the screening, diagnostics and treatment of breast tumors from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the followup. Suggestions for improvement of the current Hungarian practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The guidance has been in agreement with the related medical disciplines.

Indolepropionic Acid, a Metabolite of the Microbiome, Has Cytostatic Properties in Breast Cancer by Activating AHR and PXR Receptors and Inducing Oxidative Stress.

Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and animal experiments, we showed that IPA supplementation reduced the proportions of cancer stem cells and the proliferation, movement, and metastasis formation of cancer cells. These were achieved through inhibiting epithelial-to-mesenchymal transition, inducing oxidative and nitrosative stress, and boosting antitumor immune response. Increased oxidative/nitrosative stress was due to the IPA-mediated downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), upregulation of inducible nitric oxide synthase (iNOS), and enhanced mitochondrial reactive species production. Increased oxidative/nitrosative stress led to cytostasis and reductions in cancer cell stem-ness. IPA exerted its effects through aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR) receptors. A higher expression of PXR and AHR supported better survival in human breast cancer patients, highlighting the importance of IPA-elicited pathways in cytostasis in breast cancer. Furthermore, AHR activation and PXR expression related inversely to cancer cell proliferation level and to the stage and grade of the tumor. The fecal microbiome's capacity for IPA biosynthesis was suppressed in women newly diagnosed with breast cancer, especially with stage 0. Bacterial indole biosynthesis showed correlation with lymphocyte infiltration to tumors in humans. Taken together, we found that IPA is a cytostatic bacterial metabolite, the production of which is suppressed in human breast cancer. Bacterial metabolites, among them, IPA, have a pivotal role in regulating the progression but not the initiation of the disease.

Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma is one of the most lethal cancers in both men and women, with a median five-year survival of around 5%. Therefore, pancreatic adenocarcinoma represents an unmet medical need. Neoplastic diseases, such as pancreatic adenocarcinoma, often are associated with microbiome dysbiosis, termed oncobiosis. In pancreatic adenocarcinoma, the oral, duodenal, ductal, and fecal microbiome become dysbiotic. Furthermore, the pancreas frequently becomes colonized (by Helicobacter pylori and Malassezia, among others). The oncobiomes from long- and short-term survivors of pancreatic adenocarcinoma are different and transplantation of the microbiome from long-term survivors into animal models of pancreatic adenocarcinoma prolongs survival. The oncobiome in pancreatic adenocarcinoma modulates the inflammatory processes that drive carcinogenesis. In this review, we point out that bacterial metabolites (short chain fatty acids, secondary bile acids, polyamines, indole-derivatives, etc.) also have a role in the microbiome-driven pathogenesis of pancreatic adenocarcinoma. Finally, we show that bacterial metabolism and the bacterial metabolome is largely dysregulated in pancreatic adenocarcinoma. The pathogenic role of additional metabolites and metabolic pathways will be identified in the near future, widening the scope of this therapeutically and diagnostically exploitable pathogenic pathway in pancreatic adenocarcinoma.

Microbiome-Microbial Metabolome-Cancer Cell Interactions in Breast Cancer-Familiar, but Unexplored.

Breast cancer is a leading cause of death among women worldwide. Dysbiosis, an aberrant composition of the microbiome, characterizes breast cancer. In this review we discuss the changes to the metabolism of breast cancer cells, as well as the composition of the breast and gut microbiome in breast cancer. The role of the breast microbiome in breast cancer is unresolved, nevertheless it seems that the gut microbiome does have a role in the pathology of the disease. The gut microbiome secretes bioactive metabolites (reactivated estrogens, short chain fatty acids, amino acid metabolites, or secondary bile acids) that modulate breast cancer. We highlight the bacterial species or taxonomical units that generate these metabolites, we show their mode of action, and discuss how the metabolites affect mitochondrial metabolism and other molecular events in breast cancer. These metabolites resemble human hormones, as they are produced in a "gland" (in this case, the microbiome) and they are subsequently transferred to distant sites of action through the circulation. These metabolites appear to be important constituents of the tumor microenvironment. Finally, we discuss how bacterial dysbiosis interferes with breast cancer treatment through interfering with chemotherapeutic drug metabolism and availability.

Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors.

Recent studies showed that changes to the gut microbiome alters the microbiome-derived metabolome, potentially promoting carcinogenesis in organs that are distal to the gut. In this study, we assessed the relationship between breast cancer and cadaverine biosynthesis. Cadaverine treatment of Balb/c female mice (500 nmol/kg p.o. q.d.) grafted with 4T1 breast cancer cells ameliorated the disease (lower mass and infiltration of the primary tumor, fewer metastases, and lower grade tumors). Cadaverine treatment of breast cancer cell lines corresponding to its serum reference range (100-800 nM) reverted endothelial-to-mesenchymal transition, inhibited cellular movement and invasion, moreover, rendered cells less stem cell-like through reducing mitochondrial oxidation. Trace amino acid receptors (TAARs), namely, TAAR1, TAAR8 and TAAR9 were instrumental in provoking the cadaverine-evoked effects. Early stage breast cancer patients, versus control women, had reduced abundance of the CadA and LdcC genes in fecal DNA, both responsible for bacterial cadaverine production. Moreover, we found low protein expression of E. coli LdcC in the feces of stage 1 breast cancer patients. In addition, higher expression of lysine decarboxylase resulted in a prolonged survival among early-stage breast cancer patients. Taken together, cadaverine production seems to be a regulator of early breast cancer.

Short- and Long-Term (10-year) Results of an Organized, Population-Based Breast Cancer Screening Program: Comparative, Observational Study from Hungary.

BACKGROUND: A nationwide breast cancer screening program was introduced in Hungary in the year 2002 for women aged 45-65 years to be performed biannually. METHODS: To investigate and report the short-term and 10-year follow-up results, we analyzed our Breast Unit's prospectively led database of screened (Group A) and age-matched symptomatic (Group B) patients from 2002 to 2007. We compared the clinicopathologic features of tumors and the impact of screening on surgical treatment, as well as the overall (OS), disease-specific (DSS) and disease-free survival (DFS) of different groups. RESULTS: Data from 208 screen-detected and 101 symptomatic patients between 45 and 65 years of age were examined. Screen-detected women were younger (54 vs. 58.5 years; p = 0.001) had significantly smaller tumors (15.5 vs. 17 mm; p = 0.044), and more breast-conserving surgery (68.8 vs. 59.4%; p = 0.032). Survival statistics were not statistically different at the median follow-up of 123 months; however, there was a trend toward improved DFS in Group A (82.7 vs. 74.3%; p = 0.074). CONCLUSIONS: Our study showed a significant reduction in rates of mastectomy in the screen-detected group in the short term, which does not translate into better survival rates based on initial long-term data. In order to realize the real advantage of this newly enstated screening program, a longer period of investigation is needed.

[Use of imaging methods in the current screening, diagnostics and treatment of breast cancer - Professional guidelines. 3rd Breast Cancer Consensus Meeting]. / A képalkotó vizsgálómódszerek alkalmazása az emlõdaganatok korszerû szûrésében, diagnosztikájában és ellátásában - Szakmai útmutató a III. Emlõrák Konszenzus Konferencia alapján.

Breast radiologists and nuclear medical specialists have refreshed their previous statement text during the 3rd Hungarian Breast Cancer Consensus Meeting. They suggest taking into consideration this actual protocol for the screening, diagnostics and treatment of breast tumors, from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the follow-up. Suggestions for improvement of the Hungarian current practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The statement text has been cross-checked with the related medical disciplines.

Predictive Factors for Positive Margin and the Surgical Learning Curve in Non-Palpable Breast Cancer After Wire-Guided Localization - Prospective Study of 214 Consecutive Patients.

To investigate the most commonly used technique, the wire-guided localization (WGL) in non-palpable breast cancer. To analyze the effective factors on positive surgical margins in our practice and determine the surgical learning curve of this method. Prospective consecutive study was performed from January 2005 to December 2011. Inclusion criteria was a non-palpable breast lesion with malignancy on preoperative histology. All lesions were localized by ultrasound or stereotactic guided wire placement. Margins 1 mm or closer were accepted as positive margins which required re-excision. To determine the learning curve of WGL method we investigated the change in the reoperation rate after primary procedure performed by "high-volume" surgeon. Two hundred and fourteen consecutive patients were enrolled. In 23 patients (10.7%) reexcision was needed. Positive surgical margins were significantly influenced by the patient's age (p = 0.03), tumor volume (p < =0.001), proportion of tumor volume/specimen volume (p < 0.001), presence of DCIS (p < 0.001), multifocality (p = 0.03) and the learning curve (p = 0.006) with univariate analysis. Only the tumor volume, presence of DCIS and the learning curve were proved as independent prognostic factor for reoperation by multivariate analysis. The reoperation rate decreased below 20% after the fortieth operation. Results of our single institutional study suggest, that this localization technique can be performed safely with very good results after 40 procedures as a learning curve for surgeons.

Role of core needle biopsy in the treatment of radial scar.

Invasive tumor or ductal carcinoma in situ occur in radial sclerosing lesions in one third of the cases therefore, surgical excision is mandatory. Forty-five patients with radial scar morphology were examined. Ultrasound guided fine-needle aspiration biopsy (FNAB) and core biopsy (CB) were performed in all cases. The postoperative pathological findings were compared to the results of preoperative biopsies. Sensitivity of preoperative percutaneous biopsies (FNAB and CB) was 17.6% and 70.6%, false-negative rate was 82.4% with FNAB and 29.4% with CB. The negative predictive value was 48.1% and 84.8% respectively. Had we done preoperative cytology only, we would have had to perform a two-step procedure (sentinel lymph node biopsy) in 7 patients (15.6%), while with preoperative core biopsy it has decreased to 2 patients (4.4%). Preoperative CB in small radial stellate lesions is recommended to achieve accurate diagnosis in order to avoid a two-step surgical procedures.