CASCADE III: Designing risk-stratified models of survivorship care for HBOC and Lynch syndrome families

CASCADE is a Swiss, multicenter, family-based, open-ended, prospective cohort established in 2017 by contacting individuals with pathogenic variants (PV) associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) and their biological relatives. The cohort includes individuals with PV who are either affected or unaffected by cancer, relatives without the familial PV (true negatives), and relatives who did not have genetic testing (cascade screening). Self-administered questionnaires collect information on epidemiological factors (e.g., cancer status) and risk management behaviors (e.g., risk reducing surgeries) approximately 18-24 months apart.

Since the initiation of the cohort we have examined rates of cascade screening among relatives and family communication of genetic risk (CASCADE I); and guideline-concordant cancer surveillance and risk reducing practices (CASCADE II). CASCADE III will focus on individuals from HBOC and LS families whose cancer surveillance and risk management behaviors do not correspond to the expectations of the healthcare system (discordant behaviors). We hypothesize that discordant behaviors may be related to the characteristics of the healthcare system and/or its responses to the needs of these individuals.

CASCADE III will: Aim 1: Examine the influence of individual domain clusters (e.g., cancer status), interpersonal domain clusters (e.g., partner status), and healthcare system domain clusters (e.g., provider specialty) on cancer risk management behaviors, and explore how changes in these clusters impact changes in risk management. Aim 1 will be addressed with two (additional) questionnaires approximately 24 months apart. Combined data will cover a period of close to 10 years and 6 data collection points for participants who have been in the cohort since its initiation - currently 461 carriers of pathogenic variants (index cases and relatives), and 86 untested or ‘true negative’ individuals. Newly-identified carriers and their biological relatives will also be recruited. Risk management behaviors will be analyzed longitudinally, in light of the trajectory of the person, using survival analyses.

Aim 2: Explore decision-making processes and the perceived role of providers and the healthcare system among individuals from HBOC and LS families with discordant cancer surveillance, risk management, and genetic testing behaviors. Aim 2 will be addressed with questionnaire and narrative data. Subgroups of individuals with discordant risk management behaviors (e.g., female, over 45 years old, without risk-reducing salpingo-oophorectomy) will be invited to participate either in in-depth interviews or in focus groups. Data will be analyzed with thematic analysis.

Aim 3: Design improvements in the healthcare system based on risk-stratified “survivorship care” models for families harboring HBOC or LS pathogenic variants. Aim 3 will be addressed with a Delphi survey of a panel with international and national experts and patient representatives. The panel will explore models of risk-stratified survivorship care for HBOC and LS families. Delphi methodology is based on the principle that decisions of an expert panel are more accurate than those of unstructured groups, given adequate diversity and representativeness of panel members.