Guide to Hereditary Cancer Indications for Referral

Guide to Hereditary Cancer Indications for Referral

This tool was developed to help clinicians identify patients that would benefit from risk evaluation, genetic counseling and possible genetic testing for hereditary cancer syndromes.

This tool primarily assesses a patient’s risk of hereditary breast and ovarian cancer syndrome (HBOC), and Lynch syndrome (LS).

The Centers for Disease Control and Prevention Public Health Genomics program classifies these two conditions as Tier 1 conditions – those for which there is sufficient evidence that identifying and appropriately managing individuals at increased risk improves health.

This tool does not identify individuals at risk for all hereditary cancer syndromes. If you have questions or concerns about your patient’s risk, contact a genetics provider.

How to Use this Tool

  1. Go through the questions with your patient.
  2. For each question, indicate “yes” or “no,” then use the buttons that appear to go to the next section.
  3. This risk assessment will give you two possible outcomes:
    1. If your patient is found to have an increased risk of hereditary cancer, you will be directed to take action.
    2. If your patient does not meet any of the criteria for hereditary cancer risk, you will be directed to manage their care as appropriate.


Each question is color-coded to indicate whether your patient is at risk for a particular cancer predisposition syndrome. As such:

  • A “yes” to a question in the orange section indicates an increased cancer risk based on a specific gene identified via tumor profiling or a blood relative with a known mutation (pathogenic variant) in a cancer susceptibility gene.
  • A “yes” to a question in the pink section indicates an increased risk of HBOC
  • A  “yes” to a question in the blue section indicates an increased risk of Lynch syndrome
  • A “yes” to a question in the purple section indicates an increased risk of HBOC, Lynch or other syndromes
  • A “yes” to a question in the green section indicates an increased risk of hereditary colorectal/polyposis syndromes


Close relative

A close relative is a 1st degree relative (parents, siblings, and children) or a 2nd degree relative (grandparents, grandchildren, aunts, uncles, and half-siblings). Information about 3rd degree relatives is also used in risk assessment, specifically related to BRCA1/2 testing criteria, and/or when a patient has a small family that makes it difficult to adequately assess risk based on just 1st and 2nd degree relatives.

Gleason score

The most common prostate cancer grading system used. It describes how aggressive the cancer is. The highest a Gleason score can be is 10.

Tumor profiling test

A genetic test that evaluates genetic changes that caused the tumor to develop.

Mismatch repair deficiency

Mismatch repair genes repair mutations that occur by chance when genes are replicated. Mismatch repair errors lead to a characteristic called microsatellite instability (MSI) that can be detected in tumor tissue using a specific type of genetic test. Immunohistochemical staining (IHC) is another test that can screen for mismatch repair deficiency by looking to see if mismatch repair proteins are expressed or missing. MSI or IHC testing should be done on all colorectal and endometrial cancers to screen for Lynch syndrome.

BRCA-related cancer

HBOC-related cancers (also referred to as BRCA-related cancers) are breast cancer (male and female), ovarian cancer (including fallopian tube and primary peritoneal cancer), high grade (Gleason score ≥7) or metastatic prostate cancer, pancreatic cancer, and melanoma.

LS cancer

Lynch syndrome-related cancers and tumors are colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, pancreatic cancer, ureter and renal pelvis cancer, brain tumors (usually glioblastoma), biliary tract cancer, small intestinal cancer, sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas.