Search

Introduction: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. Methods: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. Results: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. Conclusions: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing. [ABSTRACT FROM AUTHOR]

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective study was to assess the risk factors for developing ipsilateral breast tumor reappearance (IBTR) and de novo contralateral breast cancer (BC) after primary BC treatment. Methods: Retrospectively, 15,168 consecutive patients with primary monolateral BC were enrolled in this monocentric study (from June 1994 to December 2006). Clinicopathological features, follow-up, and survival at 15 years were considered for statistical analysis. Results: Significant associations of increased risk for IBTR were verified with metastatic axillary lymph nodes (HR 1.37 [1.15–1.62], p = 0.0004), high tumor grade G2 (HR 1.35 [1.05–1.74], p = 0.02) and G3 (HR 1.35 [1.01–1.79], p = 0.04), luminal B (HR 1.51 [1.25–1.82], p < 0.0001), and HER2-positive (HR1.66 [1.14–2.41], p = 0.008) and triple-negative subtype (HR 1.54 [1.07–2.21], p = 0.02). Older age (HR 1.44 [1.08–1.91], p = 0.01) and positive family history (HR 1.85 [1.47–2.32], p < 0.0001) were risk factors for contralateral BC. Significant protective factors for IBTR were hormonotherapy (HR 0.71 [0.59–0.85], p = 0.0003), chemotherapy (HR 0.72 [0.60–0.87], p = 0.001), and radiotherapy (HR 0.73 [0.61–0.87], p = 0.0005). Hormonotherapy was also confirmed as a protective factor for contralateral second BC (HR 0.43 [0.30–0.60], p < 0.0001). Conclusions: We classified factors for IBTR and contralateral BC in high- and low-risk groups. In the high-risk group, breast surgery still remains more important than in the low-risk group, which seems to benefit more from adjuvant treatments. [ABSTRACT FROM AUTHOR]

Background: Increased C-reactive protein (CRP) is a known predictor of vascular events in asymptomatic individuals and stroke patients. Only a few studies included transient ischaemic attack (TIA) patients. We assessed CRP levels in addition to traditional risk factors in a cohort of patients with TIA to examine the relationship of these parameters to the occurrence of ischaemic stroke. Methods: This is a prospective, longitudinal clinical evaluation of the efficacy of CRP as a prognostic indicator. CRP levels were measured in 194 TIA patients and in 1,024 asymptomatic individuals (recruited from a project on stroke prevention, the PrATO, which was ongoing at the same time in the Aosta Valley). A clinical risk score was determined using the ABCD2 score in TIA patients. The area under the receiver operating characteristic curve (AUC) was used to evaluate the significance of the markers as predictors. Two models were evaluated: model 1 used the ABCD2 score and model 2 used serum CRP levels in addition to the ABCD2 score. The primary outcome was an ischaemic stroke. Results: Within 2 years ischaemic strokes occurred in 33/194 patients. The Cox proportional hazards models, after adjustments for conventional risk factors, identified CRP levels ≥3 mg/l and ABCD2 scores ≥4 as independent predictors of stroke. The corresponding AUCs were 0.565 and 0.636, based on model 1 and model 2, respectively; this represented a statistically significant difference (p = 0.043). The absolute integrated discrimination improvement was 0.0249 (p = 0.007) and the relative integrated discrimination improvement was 2.3710. The net benefit became significant from a predicted probability ≥10% and was 0.077 when based on model 1 and 0.087 when based on model 2. Conclusions: Routine CRP measurements in the acute phase might be a useful tool for identifying TIA patients who are at a higher risk of ischaemic stroke. The additional use of CRP levels for the risk assessment in TIA patients improves risk definition in terms of the ABCD2 score alone. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Only 1% of diffuse gastric cancers occur in families with autosomal dominant gastric cancer susceptibility. Germline mutations in the E-cadherin gene account for the hereditary diffuse gastric cancer (HDGC) syndrome. We studied a large cohort of gastric cancer patients from Tuscany, a region in Italy, to evaluate the presence of familial clustering of gastric cancer. Methods: 238 pedigrees were retrospectively studied by structured interviews. All probands with diagnosed gastric cancer were contacted in-person or by phone and tumor types were assessed in first- and second-degree relatives. Familial aggregation was investigated in order to search for families with suspected HDGC. Results: Familial aggregation for gastric cancer was observed in 79 of 238 cases (33.2%). Among these, there were 64 families (81%) with one gastric cancer other than the proband, 10 families with two gastric cancers (12.7%) and 5 families with three gastric cancers (6.3%). Fourteen families fulfilled the HDGC clinical criteria, one of them presenting with a pathogenic germline mutation in the E-cadherin gene (7.1%). Conclusions: The prevalence of familial HDGC appears extremely high. Since only one pathogenic germline mutation was noted in a family fulfilling the HDGC clinical criteria, factors other than E-cadherin gene mutations may contribute to the familial clustering of HDGC. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]