Clinical trial NCT03124212: Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
Official title: Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Breast and Ovarian Cancer
Lynch Syndrome
Keywords: mutation carrier
blood relative
genetic testing
family-based cohort
Lead sponsor: University of Basel
Sponsor class: OTHER
Collaborators: name: Kantonal Spital Solothurn, Olten
name: Kantonal Spital Wallis, Sion
name: Kantonal Hospital Lucerne
First posted: 2017-04-21
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Living carriers of pathogenic mutations associated with HBOC and LS, and their blood relatives (first- and second-degree, and first cousins)

Brief summary: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland and affect more than 12,000 individuals annually. Several hundred of these patients are likely to carry known genetic mutations associated with HBOC or LS. Genetic testing for hereditary susceptibility to cancer can prevent many cancer deaths through early identification and engagement in high-risk management care that involves intensive surveillance, chemoprevention and/or prophylactic surgery. However, current rates of genetic testing indicate that many Swiss mutation carriers and their family members do not use cancer genetic services (counseling and/or testing), either due to lack of coordination of care or due to lack of communication about the mutation among family members.

Cascade screening identifies and tests family members of a known mutation carrier. It determines whether asymptomatic family members are carriers of the identified mutation and proposes management options to reduce harmful outcomes. Robust evidence of basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for HBOC and LS. However, translation of this knowledge into public health interventions is lacking.

Specific Aims of the CASCADE study are:

1. Survey Index Patients diagnosed with HBOC or LS from clinic-based genetic testing records and determine their cancer status and surveillance practices; needs for coordination of medical care; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to serve as advocates for cancer genetic services for blood relatives.
2. Survey first- and second-degree relatives, and first cousins identified from pedigrees and/or family history records of HBOC and LS Index Patients and determine their cancer and mutation status; cancer surveillance practices; needs for coordination of medical care; barriers and facilitators to using cancer genetic services; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to participate in a study designed to increase use of cancer genetic services.
3. Explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and blood relatives.

Detailed description: Please see study protocol provided in the references

Eligibility criteria: Inclusion Criteria:

1. Carrier of a mutation associated with HBOC or LS
2. Have at least one living blood relative
3. Men and women
4. 18 years old and older
5. Mentally and physically able to provide informed consent
6. Can read and speak German or French or Italian or English
7. Currently living in Switzerland.

Exclusion Criteria:

1. Carriers of unclassified variants (VUS) in BRCA1, BRCA2 or MLH1, MSH2, MSH6, PMS2, EPCAM genes
2. Not living in Switzerland
3. Patients who are critically ill and cannot complete the CASCADE survey
4. Participants who are institutionalized (e.g., nursing homes) or incarcerated

Primary outcomes:
measure: Establishing the CASCADE Cohort
timeFrame: 12 months
Secondary outcomes:
measure: Cancer Surveillance
timeFrame: 12 months
Other outcomes:
Locations:
city: Delémont
country: Switzerland
facility: Hôpital du Jura Service d'Oncologie
state: Jura
city: Winterthur
country: Switzerland
facility: Katonsspital Winterthur Tumorzentrum Brustzentrum
state: Zurich
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Zvizzera Italiana
city: Bern
country: Switzerland
facility: Gastroenterology clinic
city: Bern
country: Switzerland
facility: Universitatklinik fur Medizinische Onkologie, Inselspital
city: Fribourg
country: Switzerland
facility: HFR Fribourg - Hôpital Cantonal
city: Geneva
country: Switzerland
facility: Unite d'Oncogenetique et de Prevention des Cancers
city: Geneva
country: Switzerland
facility: Hirslanden Clinic Des Grangettes
Study officials:
affiliation: University of Basel
name: Maria C Katapodi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Katapodi MC, Viassolo V, Caiata-Zufferey M, Nikolaidis C, Buhrer-Landolt R, Buerki N, Graffeo R, Horvath HC, Kurzeder C, Rabaglio M, Scharfe M, Urech C, Erlanger TE, Probst-Hensch N, Heinimann K, Heinzelmann-Schwarz V, Pagani O, Chappuis PO. Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol. JMIR Res Protoc. 2017 Sep 20;6(9):e184. doi: 10.2196/resprot.8138.
citation: Nikolaidis C, Ming C, Pedrazzani C, van der Horst T, Kaiser-Grolimund A, Ademi Z, Buhrer-Landolt R, Burki N, Caiata-Zufferey M, Champion V, Chappuis PO, Kohler C, Erlanger TE, Graffeo R, Hampel H, Heinimann K, Heinzelmann-Schwarz V, Kurzeder C, Monnerat C, Northouse LL, Pagani O, Probst-Hensch N, Rabaglio M, Schoenau E, Sijbrands EJG, Taborelli M, Urech C, Viassolo V, Wieser S, Katapodi MC; for the CASCADE Consortium. Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop. Public Health Genomics. 2018;21(3-4):121-132. doi: 10.1159/000496495. Epub 2019 Jan 29.