Suspected Hereditary Cancer Syndrome
Who Should Be Referred for Cancer Genetic Risk Assessment
Guidelines Adapted From
Hereditary Breast and Ovarian Cancer Syndrome
Personal or family history of breast cancer diagnosed <40 years of age;
Personal or family history of male breast cancer, any age;
Personal or family history of epithelial ovarian cancer, any age;
Personal or family history of triple negative breast cancer diagnosed <50 years of age
Family with 2 or more breast cancers, at least one aged < 50 years of age;
Family with both breast and epithelial ovarian cancers;
Two or more tumours in the same patient (bilateral breast cancer; multiple breast cancers; breast and ovarian cancer);
Known BRCA1/2 mutation in family
An a priori 10% probability of finding a mutation based on predictive models such as BRCAPRO, BOADICEA or Manchester Scorea
( Special note: BRCA1/2 mutation carriers are also at risk for pancreatic and prostate cancer and clinicians should additionally ask for these cancers in taking the family history. Physicians should consider referring families with breast cancer and young onset pancreatic or prostate cancer diagnosed before age 50. )
European Society for Medical Oncology (ESMO) Guidelines Working Group (2011)
Lynch Syndrome (LS)
Tumour microsatellite instability (MSI) and/or Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins should be considered in1
1. Patient with CRCbdiagnosed <50;
2. Patient with synchronous or metachronous CRC or other LS-related tumoursc, regardless of age;
3. Patient with CRC diagnosed <60 years of age with the MSI-Hdhistology (presence of tumour infiltrating lymphocytes, Crohn's-like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern)
4. Patient with CRC diagnosed at any age, and who has at least one first-degree relative diagnosed with CRC or LS-related tumour diagnosed <50 years;
5. Patient with CRC at any age, and who has two or more first- or second relatives with CRC or LS-related tumour at any age
1 Alternatively, patients fulfilling these criteria may be referred to a cancer genetics clinic for genetic evaluation and workup.
( Special note: If an MSI unstable tumour harbours the BRAF gene p.V600E mutation, it is most likely sporadic and germ line testing for mismatch repair genes is not necessary. )
When referral for clinical germline testing for mismatch repair genes should be considered:
1. Meets Amsterdam criteriaeor any of the above 5 listed criteria for tumour MSI or IHC testing for MMR proteins
2. Endometrial cancer <50 years;
3. Known LS mutation in family;
( Special note: Consider testing individuals with 10% risk of LS on any mutation model39-44(e.g., MMRpro, PREMM, MMRpredict )a
ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (2013)
National Comprehensive Cancer Network Guidelines - Genetic/ Familial High Risk Assessment Colorectal (2014)
Familial Adenomatosis Polyposis (FAP)
1. Patients with classic FAP (>100 adenomas) should be advised to pursue genetic counselling and genetic testing, particularly if they have siblings or children who could potentially benefit from predictive testing.
2. Patients with classic FAP, in whom APC genetic testing is negative, should undergo genetic testing for bi-allelic MYH mutations.
3. Patients with 10 100 adenomas can be considered for genetic testing for attenuated FAP and if negative, for MYH associated polyposis.
( Special note: It should be highlighted that the number of adenomas is the cumulative number of adenomas seen in a patients lifetime. )
American College of Gastroenterology - Medical Specialty Society 2009
aThis assessment should be made by a trained cancer genetics specialist;bCRC: colorectal cancer;cLS-related cancers include cancers of the endometrium, stomach, pancreas, small intestine, ovary, kidney, brain, ureters, or bile duct;dMSI-H: microsatellite instability (high);eAmsterdam criteria: At least 3 family members affected with cancer, spanning two generations, with at least one affected family member diagnosed below age 50 years; the 3 affected family members have to be first degree relatives of each other. In the Amsterdam I criteria, all 3 affected family members must have colorectal cancer; in Amsterdam II criteria, the affected family members may have colorectal, uterine, small bowel, ureteric or renal pelvis cancer.