Assessing the added value of breast tumor markers in genetic risk prediction model BRCAPRO View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-05

AUTHORS

Swati Biswas, Neelam Tankhiwale, Amanda Blackford, Angelica M. Gutierrez Barrera, Kaylene Ready, Karen Lu, Christopher I. Amos, Giovanni Parmigiani, Banu Arun

ABSTRACT

The BRCAPRO model estimates carrier probabilities for the BRCA1 and BRCA2 genes, and was recently enhanced to use estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. No independent assessment of the added value of these markers exists. Moreover, earlier versions of BRCAPRO did not use human epidermal growth factor receptor 2 (Her-2/neu) status of breast cancer. Here, we incorporate Her-2/neu in BRCAPRO and validate all the markers. We trained the enhanced model on 406 germline tested individuals, and validated on a separate clinical cohort of 796 individuals for whom test results and family history are available. For model-building, we estimated joint probabilities of ER, PR, and Her-2/neu status for carriers and non-carriers of BRCA1/2 mutations. For validation, we obtained BRCAPRO predictions with and without markers. We calculated area under the receiver operating characteristic curve (AUC), sensitivity, specificity, predictive values, and correct reclassification rates. The AUC for predicting BRCA1 status among individuals who are carriers of at least one mutation improved when ER and PR were used. The AUC for predicting the presence of either mutation improved when Her-2/neu was added. Use of markers also produced highly significant correct reclassification improvements in both cases. Breast tumor markers are useful for prediction of BRCA1/2 mutation status. ER and PR improve discrimination between BRCA1 and BRCA2 mutation carriers while Her-2/neu helps discriminate between carriers and non-carriers, particularly among women who are ER positive and Her-2/neu negative. These results support the use of the enhanced version of BRCAPRO in clinical settings. More... »

PAGES

347-355

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-012-1958-z

DOI

http://dx.doi.org/10.1007/s10549-012-1958-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000823396

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22270937


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