Incorporating tumor immunohistochemical markers in BRCA1 and BRCA2 carrier prediction

Excerpt

The pathology of a patient's breast carcinoma can be highly indicative of BRCA1 mutation status. Compared to sporadic and BRCA2 deficient breast carcinomas, BRCA1 deficient carcinomas tend to be estrogen receptor (ER) negative, progesterone receptor (PR) negative, HER2 negative, cytokeratin (CK)5/6 positive, and CK14 positive [1, 2]. BRCAPRO is an accurate, widely used risk prediction model that estimates the probability that an individual carries a deleterious germline mutation in BRCA1 or BRCA2 based upon their personal and/or family history of breast and ovarian cancer. Recently, when BRCAPRO carrier probabilities were updated using a patient's pathological sub-type, in a two-step process, risk estimation was improved [3]. Here we describe how we have substantially improved BRCAPRO by directly integrating marker information into the estimation of carrier probabilities and cancer risk. …