Abstract 1842: Familial demonstration of the involvement of E-cadherine germ-line mutation in inherited invasive lobular breast carcinomas

Abstract Introduction Germline mutations of the CDH1 (epithelial cadherin, OMIM 192090) gene have been extensively studied in hereditary diffuse gastric cancer (HDGC) families. Carriers of CDH1 germline mutations have a cumulative gastric cancer risk of 40-67% for men and 63-83% for women. Putative associated risk of lobular breast cancer(LBC) has also been documented in some HDGC families. Here we report a 86 members family, with a deleterious CDH1 germline mutation identified in 3 LBC affected members on 2 successive generations, 2 of them being bilateral LBC cases. It is noteworthy that no DGC was observed in this family. Subjects and Methods The family is of Caucasian origin, with 5 women affected by breast cancers. The proband is a female diagnosed with ILBC at the age of 60, her daughter was diagnosed with bilateral ILBC at the age of 42, one of her sisters died of breast cancer diagnosed at the age of 53, histological type was unknown. Two of her cousins were also diagnosed with breast cancer at the age of 63 and 54 respectively (one is a bilateral ILBC, another unknown). There is no confirmed diffused gastric cancer diagnosis in the history of this family. The affected members, their offspring, and siblings were recruited for genetic consultation. Two independent blood samples were tested after signing informed consent for each family member. Complete screening of CDH1, BRCA1 and BRCA2 genes was performed on 7 cases by sequencing exons and intron-exon boundaries. Results No BRCA1 and BRCA2 mutations were found in the family. A CDH1 Q95X germ-line mutation was found in all the 3 living women with invasive lobular breast cancers (2 of them developed bilateral ILBCs) and a 71-year-old healthy male member (one of the brothers of the proband). The mutation is also present in an obligatory carrier woman who developed a pancreatic cancer at the age of 56. Gastrointestinal endoscopy was recommended for indicative living individuals during genetic consultations, when they harbored the CDH1 mutations. No suspected gastric lesion was found. Conclusion Our report demonstrates the first clear example of the involvement of a deleterious E-cadherine germ-line mutation in inherited invasive lobular breast carcinoma. Screening for CDH1 mutation should be considered in families with multiple ILBC cases, even in the absence of DGC cases; ILBC risk should be considered for female carriers during consultations; prophylactic gastrectomy may not be regularly recommended in CDH1 mutations carriers without family histories of DGC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1842.