Selina Casalino

Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting

Objective The purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients. Methods Genetic testing was conducted on 2977 individuals originally referred for BRCA1 and BRCA2 hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted to PALB2 for the purposes of this study. A patient recontact decision tree was developed to assist in the returning of updated genetic test results to clinics and patients. Results Novel clinically actionable pathogenic variants were identified in the PALB2 gene in 18 participants (0.6%), the majority of whom were recontacted with their new or updated genetic test results. Eight individuals were unable to be recontacted; five individuals had already learnt about their new or updated findings from genetic testing outside the context of this study; three individuals prompted cascade testing in family members; two individuals were deceased. Conclusion Novel pathogenic variants in PALB2 were identified in 18 individuals through retrospective gene panel testing. Recontacting these individuals regarding these new or updated findings had a range of outcomes. The process of conveying genomic results within this framework can be effectively accomplished while upholding patient autonomy, potentially leading to advantageous outcomes for patients and their families.

Exploring the role of a multidisciplinary hereditary gynecologic oncology clinic in epithelial ovarian cancer risk‐reducing surgical decision‐making practices: A mixed‐methods study

AbstractIndividuals that have gynecologic reproductive organs with pathogenic variants in BRCA1 or BRCA2 (“BRCA‐positive”) have an increased risk of developing high‐grade serous ovarian cancer (HGSOC). The majority of HGSOC develops in the fallopian tubes and later spreads to the ovaries and peritoneal cavity. Therefore, risk‐reducing salpingo‐oophorectomy (RRSO) is recommended for those who are BRCA‐positive to preventatively remove their ovaries and fallopian tubes. The Hereditary Gynecology Clinic (HGC) is a provincial program in Winnipeg, Canada, that specifically targets care to the unique needs of such individuals through an interdisciplinary team of gynecological oncologists, menopause specialists, and registered nurses. A mixed‐methods study design was used to explore the decision‐making processes of these BRCA‐positive individuals who have been recommended (or who completed) RRSO and experiences with healthcare providers at the HGC influenced this decision. Individuals who are BRCA‐positive without a previous diagnosis of HGSOC and who had previously received genetic counselling were recruited from the HGC and the provincial cancer genetics program (Shared Health Program of Genetics & Metabolism). Forty‐three people completed a survey and 15 participated in an in‐depth interview about their experiences and decisions surrounding RRSO. Surveys were analyzed to compare scores on validated scales related to decision‐making and cancer‐related worry. Qualitative interviews were transcribed, coded, and analyzed using interpretive description. Participants described the complex decisions faced by those who are BRCA‐positive, which are intertwined with life experiences and circumstances including age, marital status, and family disease history. Participants interpreted their HGSOC risk through a personalized “lens” of contextual factors that impacted perceptions about the practical and emotional implications of RRSO and the need for surgery. Mean scores on validated scales evaluating the HGC's impact on decisional outcomes and preparedness for decision‐making about RRSO were not significant, indicating that the HGC played a supportive role, rather than helping with decision‐making itself. Therefore, we present a novel framework that consolidates the various influences on decision‐making and connects them to the psychological and practical implications of RRSO in the context of the HGC. Strategies for improving support, decisional outcomes, and the overall experiences of individuals who are BRCA‐positive attending the HGC are also described.