Germline mutations of the E‐cadherin gene in families with inherited invasive lobular breast carcinoma but no diffuse gastric cancer

BACKGROUND: Present data are highly suggestive but do not unequivocally prove the cosegregation of germ‐line CDH1 mutations with inherited invasive lobular breast cancer (ILBC). METHODS: Two Caucasian families with 6 pathologically confirmed ILBC cases but no diffuse gastric cancer (DGC) were identified in our oncogenetics consultations. Screening for mutations of CDH1, BRCA1, and BRCA2 genes was performed on blood samples. When available, loss of heterozygosity (LOH) and immunohistochemistry (IHC) analyses were performed on tumor samples. RESULTS: No BRCA1 or BRCA2 mutation was found. Deleterious CDH1 germ‐line mutations c.283C>T and c.1582del were found in all the 4 living women with ILBC in family 1 and family 2, respectively. The mutation c.283C>T was also present in a healthy 71‐year‐old male and 2 obligate carriers in family 1. No DGC was observed in the 2 families. Loss of the wild‐type CDH1 allele in 1 of the breast tumors was confirmed by LOH and IHC studies, in accordance with the “2‐hit” model of tumor suppressor genes. CONCLUSIONS: Germline CDH1 mutation can be cosegregated with ILBC in the absence of DGC. Present data do not support recommendation of prophylactic gastrectomy in CDH1 germline mutation carriers with ILBC. Cancer 2011. © 2011 American Cancer Society. Germline CDH1 mutation can be cosegregated with inherited invasive lobular breast cancer (ILBC) in the absence of diffuse gastric cancer (DGC). Present data do not support recommendation of prophylactic gastrectomy in CDH1 germline mutation carriers with ILBC.