Hereditary gastric and breast cancer syndromes with lung metastasis: narrative review of molecular and clinical insights

Background and Objective: CDH1 germline variants have been linked to hereditability in diffuse gastric (DGC) and lobular breast cancer (LBC). Although the incidence rate of these cases is relatively low, it is expected that there will be a concomitant increase in the diagnosis of germline pathogenic variants due to more frequent genetic testing. Hence, precise and selectively targeted clinical management is needed. Hereditary DGC and breast cancer syndromes are emerging entities linked to CDH1 gene germline mutations where molecular and cellular pathways are yet to be studied and described. In our review, we aimed to narrate the current state of the problem to enhance the understanding and emphasize the urging need for future investigations for identification, stratification, and management of the patients with subsequent prognosis improvement. Methods: We conducted an ample literature review from ultimate reliable online library sources to provide a summary on the contemporary syndrome understanding, where the key role in tumorigenesis belongs to CDH1 mutations and main metastatic pathways are triggered by the epithelial-to-mesenchymal transition. Key Content and Findings: E-cadherin is nowadays regarded as a tumor suppressor and its loss is related to tumor progression and metastasis formation. Other genes mutations may be involved in cell proliferation and motility enhancement. Here, we observed that one of the most common tumor patterns was signet-ring cell carcinoma, and one of common, yet insufficiently described in the literature, metastatic sites were lung. Screening guidelines and preventive surgery is proposed as an actual management trend. Conclusions: Further investigations in molecular mechanisms involved should be conducted to create precise and fulfilling molecular and genetic testing panels to identify and stratify the affected patients.