Judy E. Garber

Video Education Is an Acceptable Alternative to Pretest Genetic Counseling for Patients With Breast, Ovarian, Pancreatic, and Metastatic Prostate Cancer: Results From a Randomized Study

PURPOSE With increased demand for cancer genetic testing (GT), providers are exploring alternative service delivery models such as video education (VE). We compare the uptake of GT among 250 patients with breast, ovarian, pancreatic, or metastatic prostate cancer randomly assigned to receive either pretest VE or a pretest visit with a genetic counselor (GC). MATERIALS AND METHODS Using a 3:1 ratio, 187 patients were randomly assigned to the VE arm and 63 patients to the GC arm. GT was arranged after participants either watched an informative video (VE arm) or met with a GC (GC arm). Satisfaction, knowledge, distress, decisional regret, and family communication were assessed as secondary study end points. RESULTS Participants were age 39-88 years with no significant demographic differences between the two arms. In the VE arm, 170 (90.95%) participants completed GT versus 49 (77.8%) in the GC arm ( P = .01). The dropout rate before the pretest visit was higher in the GC arm compared with the VE arm: 10 (15.9%) versus 9 (4.8%). In the GC arm, 97.4% of participants felt all questions and concerns had been addressed compared with 66.9% of the VE arm ( P < .0001). Of the 219 participants tested, 29 (13.2%) had a pathogenic or likely pathogenic variant. CONCLUSION In this study, there was high acceptance of VE and it led to better GT uptake compared with the GC arm. However, it will be important for programs using VE to build-in more opportunities for patients to ask questions. Pretest VE is a viable option for patients with cancer who need their germline genetic test results to help guide surgical and medical decisions.

Endometrial Cancer Risk Among Germline BRCA1/2 Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps

PURPOSE To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline BRCA1/2 pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population. DESIGN A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among BRCA1/2 PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined. RESULTS Patients with BRCA1/2 PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to BRCA1/2 PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of BRCA1/2 PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions. CONCLUSION This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with BRCA1/2 PVs. Evidence-based clinical guidelines for rr-hysterectomy in BRCA1/2 PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either BRCA1 or BRCA2 PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in BRCA1/2 PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for BRCA1/2 PV carriers.

Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy

Abstract Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes.