Next Top Model: An Overview of Breast Cancer Risk Assessment Models CME REVIEW high-risk susceptibility genes, age information on unaffected family members, information on year of birth to capture birth cohort, Ash- kenazi Jewish origin, and common cancer genetic susceptibility variants (Polygenic Risk Scores). 45 The model has been validated in several studies, largely consisting of women of European ancestry, and has been found to be well-calibrat- ed. 24,46-48 However, it may not be as reliable in populations at lower risk for breast cancer or those of non-Eu- ropean ancestry. 49 Like the Tyrer-Cuzick model, the CanRisk Tool includes a diverse range of risk factors, including comprehensive family history. Addi- tionally, this is the only model that includes lifestyle risk factors such as alcohol consumption. The model is easily accessible online but requires the user to create an account for access. Unlike other models, it can be used in patients with a previous diagnosis of breast cancer. The CanRisk tool should not be used in patients with personal his- tory ductal carcinoma in situ (DCIS). Additionally, it will underestimate risk in those with Ataxia-Telangiecta- sia or homozygous carriers of patho- genic CHEK2 pathogenic truncating variants and should not be used in these patients. The CanRisk tool does not incorporate information on prior breast biopsies (number or result). Table 1 provides a summary of the factors included in several risk assessment models. Case Study A 37-year-old White female wishes to know her lifetime risk for de- veloping breast cancer. She has no significant medical history and is not Ashkenazi Jewish. She has never been tested for genetic mutations, had a mammogram, or had a breast biopsy. Menarche was at age 14, and she is premenopausal. She had a daughter at the age of 22, who is currently 15 and healthy. The patient’s mother (diagnosed at age 50, deceased age 65) and sister (diagnosed at age 44, alive (currently 47) had unilateral breast cancer (Figure 2). Her father is living, age 70, and healthy. There is no family history of ovarian cancer. Genetic test- ing for the patient’s relatives has never been performed. She is 5 foot 4 inches, weighs 150 pounds, and does not drink alcohol. She has never used hormone replacement therapy or oral contracep- tives. She has never had an SNP array/ PRS calculated. What is the patient’s lifetime risk for developing breast cancer? What are the appropriate breast cancer screening recommendations? Risk Model Assessment The Tyrer-Cuzick and CanRisk models calculate the patient’s lifetime Figure 2. A pedigree for case study 1 shows that the patient’s mother and sister were diagnosed with breast cancer. Figure 3. Lifetime breast cancer risk as calculated by the Tyrer-Cuzick (21.1%), BRCAPRO (13.0%), and CanRisk (22.3%) models for case study 1. Applied Radiology 12 January / February 2024