Atrophic gastritis is an important step in the Correa cascading pathway. It forms a pivotal period between chronic inflammation and a biologically-disrupted mucosal epithelial phenotype leading to gastric neoplasia. From a more than superficial perspective, both Helicobacter pylori (H. pylori)-associated atrophic gastritis and autoimmune atrophic gastritis converge on glandular loss and metaplastic reprogramming, but their etiologic pathways, molecular mediators, topographic distribution and neoplastic characteristics differ drastically. H. pylori infection induces multifocal atrophy and incomplete intestinal metaplasia and is the typical path to intestinal-type gastric adenocarcinoma, while autoimmune gastritis results in corpus-restricted oxyntic destruction, severe hypochlorhydria, hypergastrinemia, and a distinctive predisposition to type I gastric neuroendocrine neoplasms. Despite H. pylori eradication, the epigenetic landscape of metaplastic mucosa often persists, requiring risk-adapted surveillance approaches underpinned by histologic systems such as OLGA and OLGIM. This narrative review aggregates mechanistic, epidemiologic and clinical evidence establishing malignant potentials for both etiologies of atrophic gastritis, and offers an integrated framework for surveillance and prevention.
Identifying pathogenic/likely pathogenic variants in high-risk cancer genes is key to cancer risk management.Prophylactic surgeries like RRM and RRSO are guideline-recommended options. This study aims to provide real-world evidence on their clinical implementation. Between 2020 and 2025, 203 women referred for genetic testing at Genekor Medical S.A., were detected with P/LP variants in cancer susceptibility genes, for which risk-reducing surgical options are either recommended or considered for discussion. Referring clinicians were invited to complete a questionnaire to assess whether prophylactic surgical options had been discussed, if the patients had agreed to undergo such procedures, and whether the surgeries have already been performed or postponed. Among the individuals referred for genetic testing, 168(83%) were referred following a cancer diagnosis, while 35(17%) were unaffected individuals referred due to a family history. 153 individuals (76%) harbored BRCA1/2, 31(15%) harbored PALB2, PTEN, TP53 and 19 (9%) harbored BRIP1,RAD51C, RAD51D P/LP variants. RRSO was discussed with 78/153 (51%) of BRCA1/2 carriers and agreed in 60/78 (77%) cases. Addition of hysterectomy to RRSO was discussed in 16/78 (21%) of cases and agreed in 10/16 (63%). RRM was discussed with 113/203 (56%) of patients and agreed in 73/113(65%). In PALB2, PTEN, TP53 carriers, RRM was discussed in 21/31 (68%) cases, and accepted in 9/21 (43%), while in 5 cases both RRM/RRSO were discussed with 3 women agreeing. Finally, for 19 BRIP1,RAD51C, RAD51D carriers, in 9 cases the physician discussed RRSO as an option, with the examinees agreeing in 7 of them and in 5 cases RRM was discussed with agreement to proceed in 2 of them. In all cases, 22 individuals although agreed to proceed with RRM and/or RRSO, decided to postpone the procedure. This study highlights the high awareness and acceptance of surgical management demonstrating the adherence to the recommendations. Age under 35 years and receiving therapy at the time of genetic testing were significant factors in lowering risk reduction RRSO and hysterectomy performance rates. Stage IV cancer was the main reason for not discussing surgical intervention. K. Papazisis, M. Paraskeva, S. Giassas, M. Skondra, R. Iosifidou, C. Tolis, G. Kesisis, E. Zairi, V. Venizelos, C. Markopoulos, I. Natsiopoulos, E. Bleka, I. Xanthakis, A. Ananiadis, D. Matheos, D. Stefanou, A. Adamidis, A. Meintani, G. Kapetsis, D. Bouzarelou, E. Papadopoulou, G. Nasioulas. High-risk cancer susceptibility genes mutation carriers’ compliance with surgical risk reduction for breast and ovarian cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-05.
BACKGROUND:Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on germline pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. METHODS:A total of 9084 consecutive females with breast cancer or gynecological tumors underwent germline NGS-based genetic testing (52 cancer-relevant genes) at Genekor laboratory from 2020-2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. RESULTS:Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients <40 years to 15.90% in those ≥70 years, while Variants of Uncertain Significance (VUS) remained stable (40-43%). P/LP patients had earlier diagnosis (median 45 vs. 46 years, p < 0.001), driven predominantly by high-risk genes (13.87% in <40 y vs. 7.11% in ≥70 y). BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs. 3.16% in <40 y; median diagnosis 43 vs. 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78-0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67-0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19-1.66). CONCLUSIONS:Although derived from a referral-based (and thus selected) population, these findings show that while younger patients have a higher prevalence of high-risk P/LP variants, clinically actionable findings are present across all age groups, including those ≥70 years. These results suggest that reliance on age alone to determine eligibility for genetic testing may be insufficient. Broadening access to testing beyond strict age-based criteria could improve the identification of hereditary cancer risk and inform patient management, although further evaluation in less selected populations is warranted.
Aims Cryptogenic strokes are associated with patent foramen ovale (PFO), but accurate risk assessment remains difficult. To better identify clinical and anatomical high-risk profiles, we describe a morphological classification of PFO using 3D transoesophageal echocardiography (TEE). Methods and results 3D-TEE was performed in 95 consecutive patients with a right-to-left shunt. A classification was made based on the internal geometry: 'cone type' (wider left atrial end) and 'funnel type' (wider right atrial [RA] end). Morphology was related to the clinical history of ischaemic stroke or transient ischaemic attack (events). Thirty-seven (38.9%) had prior events. This group had a larger cross-sectional area of the RA opening (48.5 [18.4-67.0] vs. 11.75 [8.6-17.9] mm(2), P = 0.002). Funnel morphology was more common in the event group (81.1% vs. 50%, P = 0.001) and was associated with more than twice the rate of events than cone morphology (50.8% vs. 19.4%, P = 0.002). On multivariable analysis, dyslipidaemia (odds ratio [OR] 21.06), smoking (OR 6.25), funnel morphology (OR 6.47), and a larger RA opening area (OR 1.026 per mm(2)) were independent predictors of events. Receiver operating characteristic analysis identified an RA opening area >15.85 mm(2) as the optimal cut-off to predict events (area under the curve 0.719). Conclusion Prior events are highly correlated with funnel-type PFO, particularly when RA opening area exceeds 15.85 mm(2). This geometry may act as an embolic 'catchment' and favour in situ thrombosis due to disturbed flow from the wide RA inlet to the narrow tunnel exit. Integration of 3D-TEE morphology with systemic risk factors such as smoking and dyslipidaemia may refine patient stratification and guide management.
PURPOSE:This exploratory analysis assessed predictive biomarkers for sacituzumab govitecan (SG) in the open-label, phase III EVOKE-01 study of SG versus docetaxel in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:Trophoblast cell-surface antigen (Trop) 2 membrane protein expression was analyzed using immunohistochemistry in the Trop-2 biomarker-evaluable population (BEP). Circulating tumor DNA (ctDNA) analyses evaluated baseline and reduction of ctDNA with treatment and identified oncogenic driver alterations (KRAS, TP53, KEAP1, and STK11) and other relevant mutations in the ctDNA BEP. RESULTS:The median overall survival (OS) with SG versus docetaxel was 8.9 versus 9.8 months [hazard ratio (HR) = 0.96; 95% CI, 0.68-1.38] and 11.8 versus 10.7 months (HR = 0.89; 95% CI, 0.60-1.32) in subgroups with Trop-2 histologic scores greater than or equal to the median and less than the median, respectively. As expected, the median OS was longest in patients with undetectable baseline ctDNA. Reduction in ctDNA was observed after the first cycle with either treatment. KRAS driver alterations and potential immunotherapy resistance mutations (TP53, KEAP1, and STK11) were negative prognostic factors. Patients with TP53 mutations derived more benefit from SG than docetaxel. SG activity was observed independent of DNA damage repair (DDR) mutations. CONCLUSIONS:Trop-2 expression did not identify patients benefiting more from SG than from docetaxel. ctDNA reduction supported SG as active therapy in NSCLC. Evaluation of clinically relevant biomarkers in NSCLC identified KRAS, TP53, STK11, and KEAP1 mutations as negative prognostic factors in these second line-treated patients. SIGNIFICANCE:The biomarker analyses of the phase III EVOKE-01 trial found that neither Trop-2 expression nor DDR alterations predicted benefit with SG versus docetaxel. Reduction in ctDNA in both treatment arms confirmed the activity of SG in this population. Further evaluation of predictive biomarkers for SG response in NSCLC is warranted.
