Addition of pathology and biomarker information significantly improves the performance of the Manchester scoring system for <i>BRCA1</i> and <i>BRCA2</i> testing

Abstract

Data from breast pathology allowed adjustment of BRCA1 and combined BRCA1/2 scores alone. There was a lack of pathological homogeneity for BRCA2, therefore specific pathological correlates could not be identified. Upward adjustments in BRCA1 mutation prediction scores were made for grade 3 ductal cancers, oestrogen receptor (ER) and triple-negative tumours. Downward adjustments in the score were made for grade 1 tumours, lobular cancer, ductal carcinoma in situ and ER/HER2 positivity. Application of the updated scoring system led to four and nine more mutations in BRCA1 being identified at the 10% and 20% threshold, respectively. Furthermore, 65 and 58 fewer cases met the 10% and 20% threshold, respectively, for testing. Moreover, the adjusted score significantly improved the trade-off between sensitivity and specificity for BRCA1/2 prediction.