Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer.

BACKGROUND: Recently introduced multigene panel testing including BRCA1 and BRCA2 genes for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study was to evaluate rates of pathogenic BRCA1/2 mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multigene testing. METHODS: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2 testing only (limited group, n = 629) to those who underwent multigene testing with 5-43 cancer-related genes (panel group, n = 337). RESULTS: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0 vs. 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5 vs. 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9 % (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. CONCLUSIONS: Multigene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly as a result of non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from up-front, more efficient, multigene panel testing.

Are octogenarians at high risk for carotid endarterectomy?

BACKGROUND: Several prospective randomized trials have proved carotid endarterectomy to be safe and effective for both symptomatic and asymptomatic patients younger than 80 years of age. Recently, carotid artery stenting (CAS) has been approved for use in selected high-risk patients. It has been proposed that being an octogenarian places patients in this high-risk category. STUDY DESIGN: All patients between the ages of 80 to 89 years undergoing carotid endarterectomy during a 12-year period were included in the study. Information included indications for carotid endarterectomy, associated risk factors, length of stay, and hospital course. Perioperative morbidity and mortality, including neurologic events and myocardial infarction, were recorded. RESULTS: A total of 103 carotid endarterectomies were performed in 95 octogenarians. Procedures were performed on 59 men and 36 women. Indications for operation included symptomatic carotid stenosis in 44 patients (43%) and asymptomatic carotid stenosis in 59 (57%). Associated risk factors included diabetes mellitus (17%), hypertension (76%), coronary artery disease (28%), hyperlipidemia (39%), and history of smoking (42%). There were 4 perioperative neurologic complications, which included 1 transient ischemic attack (0.97%), 2 minor strokes (1.94%), and 1 major stroke (0.97%). There were no deaths. CONCLUSIONS: Combined end points for adverse events are acceptable in the octogenarian. Carotid endarterectomy remains the gold standard for treatment of extracranial carotid disease in all age groups. Age alone should not place patients in the high-risk category for carotid endarterectomy.

The efficacy of MRI as an adjuvant to traditional mammography.

The objective of our study is to assess the utility of breast Magnetic Resonance Imaging (MRI) when used for indications other than those published in peer-reviewed studies. A retrospective chart review was conducted of the records of 588 women who underwent both mammography and breast MRI. Patients excluded from the study were those who had breast MRI for accepted indications based on published peer-review studies. Included on the study were the remaining 122 patients. An evaluation was then made in each case as to whether the MRI finding caused a change in the patient's management. In this review, subject age ranged from 27- to 85-years-old. The mean age of the sample was 54.5 years. Of the positive MRI results, 29 (27.7%) had additional findings. There were 25 (20.3%) subjects with a treatment change and 97 (79.5%) without. In conclusion, breast MRI affected the clinical management in 25 (20.3%) of 122 patients. The majority of the 25 patients have invasive ductal carcinoma, followed by ductal carcinoma in situ. We believe this is a significant percentage positively affected by the additional use of breast MRI. We suggest that indications for the use of breast MRI in addition to traditional breast imaging should include all patients with invasive ductal carcinoma.