The goal of this study is to understand the performance of an experimental blood test that aims to detect early tumors in patients with hereditary cancer syndromes. If this new blood test is accurate, it could be used to screen patients for cancer and allow for earlier cancer detection. The study will compare cancer detection rates between those receiving the new blood test and those receiving standard care, assess if the test leads to earlier cancer diagnosis, and evaluate its impact on patient outcomes. The study will also use questionnaires and interviews to understand how patients feel about the blood test, its incorporation into routine medical care, and perceptions of the medical value of test results. This research could lead to more effective and less invasive cancer screening for high-risk individuals.

Through the CHARM Consortium (www.charmconsortium.ca), the investigators have shown that cell-free DNA (cfDNA) profiling can enable more frequent cancer surveillance from readily accessible blood collections. The investigators are now conducting a prospective, multi-center, randomized control trial of cfDNA testing of 1,000 HCS carriers from across Canada to 1) compare cancer detection rates with and without cfDNA testing, 2) assess cancer stage shift and clinical impact reducing mortality and morbidity cancers, and 3) assess impact of access to cfDNA results on patients' quality of life and psychological distress.

Inclusion Criteria:

• Patients with a confirmed diagnosis of hereditary breast and ovarian cancer (HBOC), Lynch Syndrome (LS), Neurofibromatosis type I (NF1), Li-Fraumeni Syndrome (LFS), PALB2, and Hereditary Diffuse Gastric Cancer (HDGC), (i.e., patients with an identified pathogenic variant in the respective cancer predisposition gene, or patients with uninformative genetic testing but with a family history suggestive of the cancer predisposition syndrome).
• Patients must be receiving standard-of-care clinical assessment for cancer by a managing physician under a provincial screening program or cancer surveillance protocol.
• All patients must have signed and dated an informed consent form for this study.

Exclusion Criteria:

• Patients must not have a personal history of cancer diagnosed and treated within 3 years prior to the expected first sample collection date for this study. If a patient has a personal history of cancer, treatment must have been completed successfully at least 3 years prior to first study sample collection.
• Patients diagnosed more than 3 years prior to the expected first sample collection date, but never been treated for the cancer.
• Patients undergoing investigations for a clinical suspicion of cancer.
• Patients who are not able to comply with the protocol (i.e., tri-annual blood sample collection if randomized into the experimental cohort).

The population to be studied includes:

Any individual that underwent clinical genetic testing for hereditary breast and ovarian cancer syndrome, Lynch Syndrome, Neurofibromatosis Type 1, Li-Fraumeni Syndrome or Hereditary Diffuse Gastric Cancer, and was found to carry a detectable variant that is likely pathogenic or pathogenic.