Citations

Background— Primary cardiac tumors are rare but have the potential to cause significant morbidity if not treated in an appropriate and timely manner. To date, however, there have been no studies examining survival characteristics of patients who undergo surgical resection. Methods and Results— From 1957 to 2006, 323 consecutive patients underwent surgical resection of primary cardiac tumors; 163 (50%) with myxomas, 83 (26%) with papillary fibroelastomas, 18 (6%) with fibromas, 12 (4%) with lipomas, 28 (9%) with other benign primary cardiac tumors, and 19 (6%) with primary malignant tumors. Operative (30 day) mortality was 2% (n=6). Univariate analysis indicated that patients who underwent resection of fibromas and myxomas had superior survival characteristics in comparison to the remainder of tumor variants; these results were consistent after adjusting for age at surgery, year of surgery, and cardiovascular risk factors. Based on actuarial characteristics of the 2002 U.S. population, patients who underwent myxoma resection had survival characteristics that were not significantly different from that of an age and gender matched population (SMR 1.11, P =0.57) whereas those who underwent resection of fibromas (SMR 11.17, P =0.002), papillary fibroelastomas (SMR 3.17, P =0.0003), lipomas (SMR 5.0, P =0.0003), other benign tumors (SMR 4.63, P =0.003), and malignant tumors (SMR 101, P <0.0001) had significantly poorer survival characteristics. Furthermore, malignant tumors in younger patients were highly fatal (HR 0.899, P <0.0001). Although the most significant predictor of mortality was tumor histology, survival was also influenced the by the duration of CPB and NYHA III/IV; the impact of these risk factors varied with time. The cumulative incidence of myxoma recurrence was 13% and occurred in a younger population (42 versus 57 years, P =0.003) with the risk of recurrence decreased after 4 years. Conclusions— Surgical resection of primary cardiac tumors is associated with excellent long-term survival; patients with cardiac myxomas have survival characteristics that are not significantly different from that of a general population. Predictors of mortality are primarily related to tumor histology but also include clinical characteristics such as symptomatology and duration of CPB.

PurposeTwenty percent of individuals with a strong family and/or personal history of breast and ovarian cancer carry a deleterious mutation in BRCA1 or BRCA2. Identification of mutations in these genes is extremely beneficial for patients pursuing risk reduction strategies. Approximately 7% of individuals who have genetic testing of BRCA1 and BRCA2 carry a variant of uncertain significance (VUS), making clinical management less certain. The majority of identified VUS occur only in one to two individuals; these variants are not able to be classified using current classification models with segregation analysis components.MethodsTo develop a clinically applicable method that can predict the pathogenicity of VUS that does not require familial information or segregation analysis, we identified characteristics of breast or ovarian tumors that distinguished sporadic tumors from tumors with BRCA1 or BRCA2 mutations. Study participants included individuals with known deleterious mutations in BRCA1 or BRCA2 and individuals with classified or unclassified BRCA variants.ResultsWe applied the models to 57 tumors with 43 different deleterious BRCA mutations and 57 tumors with 54 unique classified and unclassified BRCA variants. Of the 33 previously unclassified VUS studied, we found evidence of neutrality for 21.ConclusionOur models showed 98% sensitivity and 76% specificity for predicting classified DNA changes. We classified 64% of unknown variants as neutral. Classification of VUS as neutral will have immediate benefit for those individuals and their family members. These models are adaptable for the clinic and will be useful for individuals with limited available family history.

Purpose No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.