Evaluation of Multi-Cancer Early Detection Testing in a High-Risk Population: The INFORM Study

Inclusion Criteria Group 1- Cancer Predisposition Syndrome:

• Age ≥ 22 for patients with TP53 germline pathogenic variants, age ≥ 35 for all other variants in cancer predisposing genes
• Germline genetic testing revealed pathogenic germline variants in cancer predisposing genes (list of genes typically tested listed in pre-screening document)
• Individuals with a clinically based diagnosis of a Cancer Predisposition Syndrome (examples, neurofibromatosis, Fanconi Anemia, Ataxia-Telangiectasia)

Inclusion Criteria Group 2 - Familial Risk:

• Age ≥ 45
• Adults with family history suggestive of elevated cancer risk as defined by any the criteria below, who do not fall into Group 1:

• ≥ 1 first or second degree relative on same side of the family with:

• Breast, colon, gastric, endometrial, kidney cancer at or before age 50
• Triple negative breast cancer (any age)
• Male breast cancer (any age)
• Ovarian, pancreatic, sarcoma cancer (any age)
• Neuroendocrine cancer or tumors (any age)
• Metastatic prostate cancer (any age)
• Multiple primary cancers (example bilateral breast cancer)
• ≥ 2 first or second degree relative on same side of the family (any combination is acceptable) with breast or prostate cancer at any age

Exclusion Criteria

• Individuals diagnosed with invasive malignancy within 3 years of enrollment
• Have had a blood-based multi-cancer screening test within last year
• Individuals with evidence of symptomatic or active cancer requiring active therapeutic intervention at the time of participation (hormone therapy for breast/prostate cancer is considered acceptable and will not preclude participation)
• Individuals in Group 2 whose family history of cancer was the result of a germline mutation in a cancer predisposing gene and who have tested negative for that same familial germline mutation
• Individuals in Group 2 whose family history of cancer is sex-specific and who is a different sex than the proband with cancer (e.g., a male with a family history of endometrial or ovarian cancer would not be eligible)
• Individuals in process of being evaluated for clinical suspicion of cancer
• Individuals who have undergone a cancer risk-reducing surgery for hereditary cancer risk (e.g., mastectomy)