ABSTRACT
PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Gene Expression Profiling/standards , Genetic Testing/standards , Mutation , Practice Guidelines as Topic/standards , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Genetic Predisposition to Disease , Guideline Adherence/standards , Heredity , Humans , Middle Aged , Pedigree , Phenotype , Predictive Value of Tests , Prospective Studies , Registries , Reproducibility of Results , Risk Factors , Transcriptome , Young AdultABSTRACT
BACKGROUND: Bispectral Index (BIS)-guided anesthesia administration has been reported to reduce the time to tracheal extubation. However, no trials have compared the ability of BIS guidance to promote earlier tracheal extubation relative to guidance by end-tidal anesthetic concentration (ETAC). We hypothesized that BIS-guided anesthesia would result in earlier tracheal extubation compared with ETAC-guided anesthesia in fast-track cardiac surgery patients. METHODS: This study consisted of patients at a single institution who were enrolled in the larger, multicenter BIS or Anesthesia Gas to Reduce Explicit Recall (BAG-RECALL) clinical trial that compared rates of postoperative awareness for patient whose anesthetic was guided by BIS versus ETAC. Patients undergoing cardiac surgery were randomized to BIS (n = 361) or ETAC (n = 362) guided anesthesia. Volatile anesthetic was titrated either to maintain a BIS value of 40 to 60 (BIS group), or an age-adjusted minimum alveolar concentration of 0.7 to 1.3 (ETAC group). In the ETAC group, anesthesiologists were blinded to the BIS values. In this substudy, time to tracheal extubation was compared between groups. Cox regression identified predictors affecting the instantaneous probability of tracheal extubation. RESULTS: Time to tracheal extubation was not significantly different between groups (odds ratio 1.04, 95% confidence interval, 0.88-1.23, P = 0.643). In addition, group assignment did not influence the instantaneous probability of tracheal extubation (P = 0.433). Predictors decreasing the instantaneous probability of tracheal extubation included higher body mass index (P = 0.001), higher logistic EuroSCORE (P = 0.015), complex surgery type (P = 0.034), and surgery completion in the evening (P = 0.03). CONCLUSIONS: Compared with management based on ETAC, anesthetic management based on BIS guidance does not strongly increase the probability of earlier tracheal extubation in patients undergoing fast-track cardiac surgery. The decision to extubate the trachea is more influenced by patient characteristics and perioperative course than the assignment to BIS or ETAC monitoring.