Somatic Tumor Profile Analysis in a Patient with Germline PMS2 Mutation and Synchronous Ovarian and Uterine Carcinomas.

Lynch syndrome patients with synchronous endometrial and ovarian cancer (SEOC) are rare. When these cases occur, they are most often endometrioid histology and early grade. Early-grade tumors are not often sent for somatic tumor profiling. We present a 39 year old SEOC patient with germline PMS2 Lynch syndrome and clinical tumor analysis leading to insight regarding the origin and cause of these tumors, with potential therapy options. PMS2-related SEOC is less common due to lower risks for these cancers associated with germline PMS2 mutation compared to other Lynch genes. While synchronous cancers are not common, they are more likely to occur with Lynch syndrome. Tumor profiling with next-generation sequencing of 648 genes identified sixteen shared somatic actionable and biologically relevant mutations. This case is a rare example of a patient with PMS2 germline Lynch syndrome with shared somatic variants that demonstrate clonality of the two tumors arising from one common site.

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.

Preoperative Panel Testing for Hereditary Cancer Syndromes Does Not Significantly Impact Time to Surgery for Newly Diagnosed Breast Cancer Patients Compared with BRCA1/2 Testing.

BACKGROUND: This study seeks to determine whether there is a delay in time to surgery in breast cancer patients with panel tests compared with traditional BRCA testing. METHODS: This study was a retrospective review of women diagnosed with breast cancer who underwent genetic evaluation from our institution's Genetic Counselor Database from January 2013 to August 2015. Patients were excluded if they were male, clinical information was unavailable, the patient underwent neoadjuvant chemotherapy, had a diagnosis of recurrent breast cancer during time of study, or had postoperative genetics evaluation. RESULTS: Included in the study were 138 patients. The time from diagnosis to surgery for BRCA1/2 tested patients was 43.5 days compared with 51.0 days in the panel group (p = 0.186). Turnaround time for genetic testing decreased during the period studied and was approximately 6 days longer for panel testing than BRCA testing. It took 12.2 days for BRCA results and 18.9 days for the panel results (p < 0.01). Turnaround time for BRCA1/2 testing in 2014 and 2015 was 12.4 and 10.5 days respectively, whereas panel testing was 20.5 and 18.2 days (p ≤ 0.001). Of the variables included in multivariable linear regression, only mastectomy significantly contributed to time to surgery (p < 0.001). DISCUSSION: Panel genetic testing did not delay time to surgery compared with BRCA testing alone. The use of panel testing has increased over time, and lab turnaround time has decreased. Mastectomy was the only clinical variable contributing to longer time to surgery.

Differences in physician referral practices and attitudes regarding hereditary breast cancer by clinical practice location.

PURPOSE: To compare physician referral practices and attitudes regarding hereditary breast cancer by clinical practice location. METHODS: A self-administered survey of 214 physicians in Ohio's tri-state region. RESULTS: Rural-practice physicians were less likely to have ever referred for an indication of hereditary breast cancer than urban- and suburban-practice physicians combined. Rural-practice physicians reported stronger barriers to referral, including distance, lack of awareness, lack of effective cancer risk reduction, and lack of patient interest. CONCLUSION: These findings demonstrate a need for increased clinical genetics outreach, physician education, and public awareness of genetic services for hereditary breast cancer in rural areas.

Clinical interpretation and recommendations for patients with a variant of uncertain significance in BRCA1 or BRCA2: a survey of genetic counseling practice.

The intent of this study was to document current practices in breast cancer genetic counseling and identify areas of variability for patients with a variant of uncertain significance (VUS) in the BRCA1 or BRCA2 gene. Registered members of the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group (SIG) were sent an invitation via electronic mail to participate in an online questionnaire. The questionnaire was divided into three sections: clinical experience, clinical meaning, and risk perceptions and clinical recommendations for clinical situations involving a VUS. Fifty-seven of the eligible members responded. During the pre-test counseling session for a BRCA risk assessment patient, the vast majority of counselors (80.7%) mention VUS as a possible test result. Nearly half, 49.1%, report having given such a result to their patients at least one to four times. However, only 63.2% felt as though their patients understood the meaning of a VUS result. When asked to conclude the implication of a VUS and make medical management recommendations, the responses were varied. Nevertheless, a good proportion of counselors expressed the importance of testing other family members to help clarify the proband's risk and aid in medical management issues. Although the recent recommendations by the American College of Medical Genetics suggest standards for the interpretation of sequence variations, they do not provide guidelines for making clinical recommendations based on these variations. The results of this study reveal significant diversity in the personal interpretation of a VUS result, leading to various clinical recommendations, and suggest a need for clinical management recommendations as well.

Breast cancer genetics education for college women: an evaluation of approaches.

BACKGROUND: A strong family history of breast cancer may greatly increase the chances for young women to develop the disease. Breast cancer genetics education for college-age women would increase awareness, but an effective method remains elusive. METHODS: Thirty-five college women viewed four education tools (CD-ROM, video, brochure, and lecture) and discussed topic importance, tool preference, and distribution ideas in focus groups. RESULTS: The participants considered breast cancer genetics important; however, the information must be made relevant to their peers to be accepted. CONCLUSION: An ideal education method would focus on general breast health, mentioning family history as an important risk factor.