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.

Abstracting height and weight from medical records, and breast cancer pathologic factors.

Cancer registries routinely collect data on clinicopathologic factors, but rarely abstract anthropometric variables. We conducted a chart review study, examining the feasibility of abstracting weight, height, alcohol use, and smoking from medical records in women (n = 1,974) diagnosed with invasive breast cancer, and investigated the association between the abstracted variables with clinicopathologic features. Qualitative data were reviewed and categorized. Frequencies of the abstracted data, and demographic and clinicopathologic variables were calculated. Logistic regression models measured the relationship between the outcome variables, tumor size, stage of disease, and estrogen/progesterone (ER/PR) status with the abstracted variables. Data on current alcohol-use/no-use, current-smoker/non-smoker, and height/weight data were obtained on 96%, 97%, and 88-89% of the participants, respectively. The multivariate analysis showed that overweight (>or=25 kg/m(2)) women had significantly larger (>or=2 cm) tumor size compared with normal weight for both women <50 years (OR = 1.79; 95% CI = 1.14-2.81; p or=50 years at diagnosis (OR = 1.58; 95% CI = 1.19-2.09; p

BRCA mutations and the risk of angiosarcoma after breast cancer treatment.

Post-breast cancer treatment-related angiosarcomas were first observed in lymphedematous extremities after mastectomy and are now being reported with increasing frequency after lumpectomy and radiation. A case history is presented of a BRCA2 carrier who had a postmastectomy chest wall angiosarcoma but had neither therapeutic radiation nor clinically evident lymphedema. The absence of established risk factors led to speculation that the BRCA2 germline mutation could be a causative factor in the development of this patient's angiosarcoma. A literature review supported this concept.

Wool Base determination using dual energy X-ray absorptiometry (DEXA).

An industry grade dual energy X-ray absorptiometry (DEXA) scanner was calibrated for Wool Base determination. The calibration used 201 Crossbred and Merino wool samples, and a further 72 samples to validate the calibration. The prediction correlation had the smallest residual standard deviation (RSD) when the independently measured mean fibre diameter (MFD) was included in the multiple regression analysis. Best results were achieved when separate calibrations were used for individual wool breeds. The RSD for the Merino calibration set of 44 samples was 1.88, when the MFD was included in the regression, and 2.1 without. The RSD for 144 Crossbred samples was 1.73 including the MFD, and 2.59 without. The validation trial with 46 Crossbred and 24 Merino wool samples resulted in RSD of 2.35 and 2.23, respectively. An excellent DEXA repeatability was achieved at a standard deviation of approximately 0.2%. Improvement of the calibration is expected from concurrent laboratory testing and scanning. The research shows the promising potential for DEXA as a tool to determine Wool Base.

Comparing neutron and X-ray-based dual beam gauges for characterising industrial organic-based materials.

Comparisons are made of the neutron gamma transmission (NEUGAT) and dual energy X-ray absorption (DEXA) methods of measuring the composition of organic-based industrial products. A simple model is developed to allow comparisons to be made particularly of the measurement precision and the industrial performance. These gauges have similar applications but the latter gauge is shown to be more suitable for high and variable product throughputs. X-ray tube source and detector combinations provide higher beam fluxes, superior imaging and require less bulky shielding.

Measuring Physicians' Performances and Marketing the RESULTS: A Breast Cancer Model.

The recent transition to managed care has intensified the public's concerns about the quality of medical care. In response, payers, who until recently seemed preoccupied with costs, are demonstrating a renewed interest in value, which in turn could lead to an expansion of negotiations with physicians to include the tracking of such issues as physician performance, patient satisfaction, and patient outcomes. As a response to public concern and demand for accountability, the medical establishment must develop methods to assist payers in estimating relative value of competing medical services. In anticipation of a values transition in their specialty, breast care, the authors established a performance-oriented database which facilitated assessments of their performance in relation to community standards, and enhanced efforts to identify and correct performance deficiencies. Year-end results were summarized in a report-card format that improved marketability. The author's experiences should be of interest to physicians who are attempting to respond to changes in the rapidly evolving medical marketplace.

Multifocal Breast Cancer in Young Women with Prolonged Contact between Their Breasts and Their Cellular Phones.

Breast cancer occurring in women under the age of 40 is uncommon in the absence of family history or genetic predisposition, and prompts the exploration of other possible exposures or environmental risks. We report a case series of four young women-ages from 21 to 39-with multifocal invasive breast cancer that raises the concern of a possible association with nonionizing radiation of electromagnetic field exposures from cellular phones. All patients regularly carried their smartphones directly against their breasts in their brassieres for up to 10 hours a day, for several years, and developed tumors in areas of their breasts immediately underlying the phones. All patients had no family history of breast cancer, tested negative for BRCA1 and BRCA2, and had no other known breast cancer risks. Their breast imaging is reviewed, showing clustering of multiple tumor foci in the breast directly under the area of phone contact. Pathology of all four cases shows striking similarity; all tumors are hormone-positive, low-intermediate grade, having an extensive intraductal component, and all tumors have near identical morphology. These cases raise awareness to the lack of safety data of prolonged direct contact with cellular phones.

Multidisciplinary management of ductal carcinoma in situ: a 10-year experience.

BACKGROUND: Two ductal carcinoma in situ (DCIS) treatment controversies are (1) what is the preferred margin for patients undergoing lumpectomy plus radiation, and (2) is there a subgroup that can be safely treated with lumpectomy alone? A multidisciplinary team was established to evaluate these issues. METHODS: Patients with DCIS who were candidates for breast-conservation were divided into 2 groups. Group 1 had a minimum 5-mm margin and received radiation, and group 2 had a minimum 10-mm margin and received no radiation. RESULTS: One hundred fifty-two patients (153 cancers) met the inclusion criteria. The median follow-up was 8.2 years. Overall, there were 6 recurrences (3.92%); 1 of 71 recurred in group 1 (1.40%), and 5 of 82 recurred in group 2 (6.01%). CONCLUSION: Five-millimeter margins plus radiation results in low rates of recurrence. A subgroup of DCIS patients can be identified in which radiation can be safely avoided. The multidisciplinary team approach to managing DCIS enhances the potential for improved outcomes.

Risk of angiosarcoma following breast conservation: a clinical alert.

Approximately 100 cases of angiosarcoma following breast-conserving therapy have been reported. The prevalence of angiosarcoma following breast conservation has not been accurately established and optimal treatment has not been defined. The goal of this article is to clarify both issues. The Fisher's exact test was used to compare the prevalence of postirradiation angiosarcoma seen in our private practice to the prevalence reported from the two largest national database studies. A literature review was performed to determine optimal treatment guidelines. The results of the comparison indicated that the prevalence of postirradiation angiosarcoma seen in our practice was significantly higher than that reported in the two national database studies at p-values of 0.0124 and 0.0080. Also, results from the literature review suggest that early detection and aggressive treatment lead to improved outcomes. The data are insufficient to draw firm conclusions, but suggest that the current literature underestimates the prevalence of angiosarcoma following breast-conserving therapy. Since elderly women derive less benefit from radiation and may be more prone to develop postirradiation angiosarcoma, confirmation of our findings could lead to a reappraisal of the management of elderly patients with early stage breast cancer.