Risk algorithms that include pathology adjustment for HER2 amplification need to make further downward adjustments in likelihood scores

AbstractTo assess the need for adjustment in the likelihood of germlineBRCA1/2 mutations in women with HER2+ breast cancers. We analysed primary mutation screens on women with breast cancer with unequivocal HER2 overexpression and assessed the likelihood ofBRCA1/BRCA2 mutations by age, oestrogen receptor status and Manchester score. Of 1111 primary BRCA screens with confirmed HER2 status only 4/161 (2.5%) of women with HER2 amplification had aBRCA1 mutation identified and 5/161 (3.1%) aBRCA2 mutation. The pathology adjusted Manchester score between 10 and 19% and 20%+ thresholds resulted in a detection rate of only 6.5 and 15% respectively. BOADICEA examples appeared to make even less downward adjustment. There is a very low detection rate ofBRCA1 andBRCA2 mutations in women with HER2 amplified breast cancers. The Manchester score and BOADICEA do not make sufficient downward adjustment for HER2 amplification. For unaffected women, assessment of breast cancer risk andBRCA1/2 probability should take into account the pathology of the most relevant close relative. Unaffected women undergoing mutation testing forBRCA1/2 should be advised that there is limited reassurance from a negative test result if their close relative had a HER2+ breast cancer.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research