Hereditary diffuse gastric cancer is a rare disorder and guidelines are based on expert opinion of the International Gastric Cancer Linkage Consortium. Updated clinical guidelines were published in 2020r based on information gathered since the original recommendations were published in 1999. The guidelines are based on observation and the outcome of research protocols.
The published diffuse gastric and lobular breast cancer risks are derived from CDH1 families ascertained because of a history of DGC. In the absence of a family history of DGC, the risk of diffuse gastric or lobular breast cancer is unclear.r
Expert consensus supports gastrectomy in asymptomatic individuals with a germline CDH1 pathogenic variant.r This is because of the high risk of death from gastric cancer, the elimination of risk of gastric cancer after gastrectomy and lack of evidence that surveillance is effective in preventing advanced gastric cancer. Endoscopy is recommended in CDH1 patients prior to total gastrectomy for staging.r
Families with a history of very early onset gastric cancer have been described,r and gastrectomy may be considered earlier than usual in these families. The impact of early gastrectomy and associated nutritional problems on normal growth and pubertal development in adolescents must be taken into account when considering the timing of surgery.
The limitations of endoscopy and nature of DGC should be explained to all patients.
For those declining or postponing gastrectomy, endoscopic surveillance should be offered. An Endoscopy Surveillance Protocol for HDGC has been developed by expert consensusr (see Supplementary Appendix Supplementary Text 1: Endoscopy Surveillance Protocol to Blair et al. 2020). Whenever possible, surveillance should occur in expert centres familiar with HDGC. Signet ring lesions are detected in gastric biopsies for 40-61% of CDH1 carriers, and a positive biopsy is most likely during the first endoscopy.rr
Surveillance should only be offered to asymptomatic individuals who would be surgical candidates for gastrectomy if gastric cancer were to be identified.
There is currently insufficient data on the role and outcome of breast cancer screening in carriers of a CDH1 pathogenic variant, so recommendations are based on the high lifetime risk of breast cancer, particularly the lobular subtype, and the precedents established in other hereditary breast cancer syndromes. MRI may be more sensitive than mammogram for detection of lobular cancer.r The addition of ultrasound to mammogram can be considered if MRI is not available or contraindicated.r
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high-risk women. There have been no studies to date to determine if it is specifically effective for the primary prevention of lobular breast cancer. In view of the potential side effects associated with tamoxifen/raloxifene, risk-reducing medications should be discussed with an experienced medical professional to determine the relevant risks and benefits in an individual pathogenic variant carrier. See COSA medication to lower the risk of breast cancer: clinician guide.
Therapeutic levels of chemopreventative agents could be compromised after total gastrectomy.