Doctors use a computer program -- a predictive model -- to help them decide which women are most likely to have an abnormal breast cancer gene. Based on the results of the model, doctors may suggest genetic testing for women likely to have an abnormal gene. Insurance companies use the same models to decide who gets coverage for genetic testing.
The study reviewed here found that two models used to predict BRCA1 and BRCA2 abnormalities aren't very accurate when used on Asian women. This could mean Asian women aren't referred for genetic testing when they should be or that insurance companies don't cover the testing even when it's recommended. The two models looked at in this study are BRCAPRO and Myriad II.
Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2). Women with an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70. Abnormal BRCA1 and BRCA2 genes are found in 5% to 10% of all breast cancer cases in the United States.
Factors that increase the risk of an abnormal BRCA1 or BRCA2 gene are:
The models doctors and insurance companies use to decide who should get genetic testing consider these and other factors, including ethnicity, to determine a woman's risk of having an abnormal breast cancer gene and whether testing makes sense for her. This study looked at how accurate the BRCAPRO and Myriad II models were in estimating the likelihood that 200 Asian women and a smaller number of white women would have an abnormal breast cancer gene.
The results:
If you're an Asian woman and you and your doctor are considering genetic testing based on your personal or family history, ask your doctor about this study. If you're an Asian woman and your doctor has said you don't need genetic testing, you should also discuss the results of this study.
No matter what your ethnic background is, if you know you have an abnormal BRCA1 or BRCA2 gene, your risk of developing breast cancer is higher than the average woman's. You can't change your genetics. But you can make sure that if breast cancer develops it's diagnosed as early as possible. You and your doctor should develop a screening plan designed for your unique situation that includes more frequent screenings that start at an early age and possibly MRI scans or other screening tests. Abnormal breast cancer genes also increase the risk of ovarian cancer, so it's important to discuss this with your doctor, too.
Visit the Genetics and Breast Cancer Risk section to learn more about abnormal breast cancer genes.
STANFORD, Calif., Sept. 15 (MedPage Today) -- Half of the Asian women who carry BRCA1/2 cancer mutations may fall through the statistical cracks of two widely used prediction models, investigators here concluded.
Both the BRCAPRO and Myriad II programs predicted 50% fewer Asian carriers than were actually observed, Allison W. Kurian, M.D., of Stanford, and colleagues reported online in the Journal of Clinical Oncology.
In contrast, both programs' predictions for white mutation carriers were virtually identical to the observed number of carriers.
"Both models' two-fold underprediction of the total number of Asian BRCA1/2 mutation carriers argues for caution in their use to guide clinical testing in patients of Asian descent," the authors concluded.
Breast cancer epidemiology differs between Asian and white populations, but knowledge about hereditary breast cancer in Asians is lacking, the researchers said.
More Asians are being tested for BRCA1/2 mutations, they continued, but the predictive accuracy of models used to guide testing had not been determined in Asians.
To evaluate the BRCAPRO and Myriad II models, the investigators recruited 200 Asian women and a control group of white women. All participants underwent testing for BRCA1/2 mutations at four cancer genetics clinics.
In the white control population, genetic testing identified 25 mutation carriers. The BRCAPRO model predicted 24, and the Myriad II predicted 25.
Genetic testing identified 49 mutation carriers in the Asian participants. However, BRCAPRO predicted only 25, and Myriad II predicted 26.
The ethnic difference with BRCAPRO reflected substantial underestimation of BRCA2 in the Asian participants, as testing identified 26 carriers but the model predicted only four. Separate mutation predictions were not available for Myriad II.
Comparison of area under the receiver operating characteristic curves for both models revealed a trend toward lower curves in the Asian participants compared with the white participants, suggesting less accurate discrimination between carriers and noncarriers in the Asian group.
The two prediction models are available as part of a free software package that can be downloaded from the Internet, the authors noted. Additionally, the models are updated regularly.
"Given their availability and their generally superior performance on validation, BRCAPRO and Myriad II are by far the most widely used models to guide BRCA1/2 mutation testing in the United States," the authors said. "Consequently, their performance in Asian-Americans has high clinical relevance, which guided our selection of these two models for the study."
The study was supported by the Susan G. Komen Breast Cancer Research Foundation. The authors reported no potential conflicts of interest.
Primary source: Journal of Clinical Oncology Source reference: Kurian AW, et al "Performance of BRCA1/2 mutation prediction models in Asian Americans" J Clin Oncol 2008; 26: DOI: 10.1200/JCO.2008.16.8310.
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