BackgroundGermline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition.MethodTo determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions.ResultsNo truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis.ConclusionPotentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.
There was no significant difference in prognosis (DFS and OS rates) between the genders, but significant differences in sociodemographic and clinical characteristics were detected between male and female breast cancer cases.
Authors PB and CRC managed the literature searches, collected the data, performed the statistical analysis, checked the analyses, drafted and revised the manuscript. Authors AB and LCST conceived the idea and its analytic strategy, checked data extraction and analyses, interpreted the findings, drafted and revised the manuscript. All authors read and approved the final manuscript.
Background: Male breast cancer is an uncommon disease and the therapy is mainly based on what is know from female breast cancer. Objective: To investigate the clinicopathologic characteristics of male breast cancer and the overall survival in a single institution. Methods: The clinical data and survival status of 75 male breast cancer treated in a Brazilian public cancer hospital from 2000 to 2009 were collected. The association with clinicopathological characteristics and overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards regression (enter method) was used to assess survival differences after adjusting for confounders. The study was approved by National Cancer Institute Research and Ethics Committee (number 128/11). Results: The median patient age was 64 years (range 33–86). Estrogen receptor (ER) was positive in 58 (77.3%) patients, while progesterone receptor (PR) were positive in 47 (62.7%). Histology type was ductal infiltrant carcinoma for 57 (76.0%) and 51 (68.0%) patients underwent surgery. The median follow-up period was 43,1 months (range 2.7–147.8). The median survival from the diagnosis of breast cancer was 97.0 months (95%CI 53.6 −140.4) with a 61.7% 5-year overall survival (OS). In the final Cox regression model, independent factors associated with increased risk of death were metastasis at diagnosis (HR = 18.1; 95%CI: 5.9–55.2), ≥ 65 years old (HR = 4.3; 95%CI: 1.7–10.5); tumor stages ≥ IIb (HR = 3.5; 95%CI: 1.3–9.7) and smoking (HR = 1.6; 95%CI: 1.04–2.6). Conclusions: Invasive ductal carcinoma is the main pathologic type. The median survival from the diagnosis of breast cancer was 97.0 months and metastasis at diagnosis, patient age, tumor stage and smoking are independent prognostic factors. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-11-04.
Background: CDH1 encodes the cell-cell adhesion molecule, E-cadherin, for which loss of expression facilitates the infiltrative and metastatic potential of cancers. Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC), and in this setting female carriers have been estimated to have a 39-50% risk of lobular breast cancer (LBC) by age 80 years. Aim: To determine the frequency of CDH1 germline mutations inindividuals with early-onset LBC or those with LBC and a family history of multiple breast cancers but no gastric cancers. Methods: Germline DNA analysis of CDH1 in women with LBC, for whom germline BRCA1 and BRCA2 mutations have been excluded, who have been (1) diagnosed before the age of 45 years or (2) diagnosed at any age and have a family history of breast cancer. Results: Analysis of 194 LBC cases has thus far revealed two novel missense mutations predicted to affect protein function. Functional assays to assess their pathogenicity along with germline analyses of the remaining 200 cases are currently underway. Several unreported silent changes have also been identified and will be measured in a case- control sample to assess whether they are associated with LBC risk. Conclusion: Germline CDH1 mutations may cause a small proportion of familial and early onset LBC.
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