Cancer genetic testing panels for inherited cancer susceptibility: the clinical experience of a large adult genetics practice.

Next-generation sequencing genetic testing panels for cancer susceptibility (cancer panels) have recently become clinically available. At present, clinical utility is unknown and there are no set criteria or guidelines established for whom to offer such testing. Although it may be a cost-effective method to test multiple cancer susceptibility genes concurrently, the rate of finding variants of unknown significance (VUS) may be high and testing may yield mutations in genes with no established management recommendations. We describe our Center's experience over a 14-month period (April 2012-June 2013) for patient interest and uptake in cancer panel testing and whether there were predictors of pursuing testing or identifying mutations. Using a clinical ranking system, patients' family histories were ranked from 0 to 3 (low likelihood to high likelihood for underlying genetic susceptibility). The clinical ranking system was assessed to determine its predictability of finding mutations. Of the 689 patients who met inclusion criteria, the option of pursuing a cancer panel was discussed with 357 patients; 63 (17.6 %) patients pursued testing. Those who pursued testing were more likely to be older, male, affected with cancer, affected with multiple primary cancers, and had a higher clinical rank than non-pursuers. There were no significant predictors of finding a mutation on panel testing. Of the 61 patients who have received results, there was a 6.6 % mutation rate and 19.7 % VUS rate. The yield of cancer panels in clinical practice is low and the strength of family history alone may not predict likelihood of finding a mutation.

10 rare tumors that warrant a genetics referral.

The number of described cancer susceptibility syndromes continues to grow, as does our knowledge on how to manage these syndromes with the aim of early detection and cancer prevention. Oncologists now have greater responsibility to recognize patterns of cancer that warrant referral for a genetics consultation. While some patterns of common cancers are easy to recognize as related to hereditary cancer syndromes, there are a number of rare tumors that are highly associated with cancer syndromes yet are often overlooked given their infrequency. We present a review of ten rare tumors that are strongly associated with hereditary cancer predisposition syndromes: adrenocortical carcinoma, carcinoid tumors, diffuse gastric cancer, fallopian tube/primary peritoneal cancer, leiomyosarcoma, medullary thyroid cancer, paraganglioma/pheochromocytoma, renal cell carcinoma of chromophobe, hybrid oncocytoic, or oncocytoma histology, sebaceous carcinoma, and sex cord tumors with annular tubules. This review will serve as a guide for oncologists to assist in the recognition of rare tumors that warrant referral for a genetic consultation.

Genetic testing by cancer site: ovary.

Approximately 1 in every 4 to 5 women with a diagnosis of ovarian cancer has a hereditary gene mutation that is responsible for the development of her cancer. Identifying women at increased risk of developing ovarian cancer due to a hereditary cancer syndrome can allow for early detection or prevention of not only ovarian cancer, but also other cancers, depending on the causative gene. This review focuses on 3 of the most common hereditary ovarian cancer syndromes, hereditary breast and ovarian cancer syndrome (the BRCA1 and BRCA2 genes), Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), and Peutz-Jeghers syndrome, including key features, genetics, and management of these syndromes. In addition, newly discovered genes (eg, RAD51C and RAD51D) linked to ovarian cancer are discussed.

Psychological impact of recall in high-risk breast MRI screening.

PURPOSE: To address the widespread concern that false-positive results during breast MRI screening may have adverse psychological effects. METHODS: Impact of Event Scale measurements in 103 high-risk women enrolled in a longitudinal MRI screening study and comparison of subjects with normal results vs. those with prior recall events. RESULTS: Of 189 MRI scans performed, 64 (34%) prompted further evaluation. Subjects with previously abnormal results had significantly higher Avoidance scores at the time of their second MRI. Multivariate analysis showed this was driven by the greater number of BRCA1/2 carriers in that group but was not related to screening recall. CONCLUSIONS: Practitioners' concerns about the high false positive rate of breast MRI may not be matched by actual psychological effects in most high-risk women.