BackgroundOver recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs.ObjectiveTo explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC).MethodsBetween 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed.Results232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes.ConclusionsThe mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.
The only independent predictor of FGP development in our study was duration of PPI therapy greater than 48 months. Increased dosage of therapy did not significantly impact the development of FGP.
Purpose: Angiogenesis has a vital role in tumor growth and metastasis, and vascular endothelial growth factor (VEGF) represents a potent cytokine in this process. However, the influence of VEGF in ovarian cancer remains controversial. Interest has focused on the use of antiangiogenic drugs in ovarian cancer. This study aims to establish the pattern of expression and effect on prognosis of VEGF in a large population of ovarian cancer patients and to potentially identify a cohort in whom antiangiogenic therapy is appropriate.
Experimental Design: Using a tissue microarray of 339 primary ovarian cancers, the expression of VEGF was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied.
Results: Tumors expressing high levels of VEGF had significantly poorer survival (P = 0.04). Factors shown to predict prognosis independently of each other were age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. VEGF was independently predictive of prognosis on multivariate analysis (P = 0.02). There was no correlation between VEGF and any clinicopathologic variable. High expression of VEGF was seen in only 7% of the tumors, suggesting that the role of antiangiogenic drugs may be limited to a small subset of patients.
Conclusion: High VEGF expression occurs in a small proportion of ovarian cancers, and this independently predicts poor prognosis. The small percentage of tumors with high levels of VEGF activity suggests that the role of bevacizumab may potentially be limited to a few patients; these patients could be targeted by molecular profiling.
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