Tyrer-Cuzick Lifetime Risk Is Not Associated With Non-BRCA1/2 Pathogenic Variants for Breast Carcinoma.

Area of Science:

• Oncology
• Genetics
• Risk Assessment

Background:

• The Tyrer-Cuzick (TC) calculator assesses breast cancer risk using multiple factors.
• Its association with non-BRCA1/2 pathogenic variants (PVs) is not well-established.
• TC guides decisions on further diagnostic imaging, genetic testing, and preventative measures.

Purpose of the Study:

• To evaluate the association between Tyrer-Cuzick (TC) scores and non-BRCA1/2 pathogenic variants (PVs) in breast cancer susceptibility genes.
• To determine if TC scores can predict the presence of non-BRCA1/2 PVs.

Main Methods:

• A cohort of 964 patients with TC scores underwent genetic testing for 12 PVs and variants of unknown significance (VUS).
• TC scores were compared among patient groups with BRCA mutations, non-BRCA PVs, and no PVs.
• Statistical analyses included Kruskal-Wallis tests, pairwise comparisons, and logistic regression with ROC curve analysis.

Main Results:

• The average TC score was 7.71%.
• 12.03% of patients had PVs, with an average TC of 8.98%.
• Patients with BRCA1/2 variants had higher TC scores compared to those with non-BRCA1/2 PVs (average TC 5.47%).

Conclusions:

• TC scores are not associated with the prediction of non-BRCA1/2 PVs.
• TC is not a reliable predictor for genetic testing panels concerning non-BRCA1/2 PVs.
• There is a need for a new genetic risk calculator incorporating predictive value for non-BRCA1/2 PVs in women with low or average TC scores.