BRCAPRO 6.0 Model Validation in Male Patients Presenting for BRCA Testing

Abstract

Background: BRCAPRO is a risk assessment model to estimate the risk of carrying a BRCA mutation. BRCA mutation carriers are at higher risk of developing breast, ovarian, pancreatic, and prostate cancer. BRCAPRO was developed for women and found to be superior to other risk assessment models. The present study evaluated the validity of BRCAPRO at predicting the risk of male patients carrying a BRCA mutation.

Patients and methods: A total of 146 men who presented for genetic counseling and testing from February1997 to September 2011, and their test results were included in the present study. BRCAPRO risk assessment for all patients was calculated using the BRCAPRO clinical CancerGene assessment software.

Results: The mean age at presentation was 57 years. Of the 146 patients, 48 had breast cancer, 18 had pancreatic cancer, 39 had prostate cancer, 27 had other primary cancers, and 37 had no cancer. Fifty patients (34%) tested positive for a BRCA mutation (22 BRCA1, 27 BRCA2, and 1 BRCA1 and BRCA2). The mean BRCAPRO score for all patients was 24.96%. The BRCAPRO score was significantly higher for patients who tested positive for a BRCA mutation (46.19% vs. 13.9%, p < .01). The area under the receiver operating characteristics curve was 0.83 for all patients for the BRCAPRO score to predict the risk of carrying a BRCA mutation. At a cutoff point of 30.02%, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.74, 0.81, 0.67, and 0.86, respectively.

Conclusion: BRCAPRO appears to be a valid risk assessment tool for determining the risk of carrying a BRCA mutation in men.

Implications for practice: Men carrying genetic mutations in the BRCA gene have a greater risk than the general population of developing certain types of cancer, including breast, pancreatic, and prostate cancer. BRCAPRO is a risk assessment model that predicts the risk of carrying a BRCA mutation. The present study aimed at validating BRCAPRO for use with men seen for genetic counseling, whether affected by cancer or not. The data available for 146 patients revealed that BRCAPRO was effective at identifying patients at risk of BRCA mutation. These findings could help in identifying a subset of high-risk patients who should proceed to genetic testing.

Keywords: BRCA; BRCAPRO; Cancer genetics; Genetic counseling; Male breast cancer; Risk models.

Figure 1.

Diagnostic test for BRCAPRO 6.0 score to predict BRCA mutations. Entire group, n = 146 (odds ratio estimate, 1.061 [95% confidence interval (CI), 1.040–1.083]). Area under ROC curve = 0.8331 (95% CI, 0.7591–0.9071). Abbreviation: ROC, receiver operating characteristics.

Figure 2.

Multivariable logistic regression analysis results. Area under ROC curve = 0.8379 (95% CI, 0.7634–0.9125). Abbreviations: CI, confidence interval; KFM, known family mutation; OR, odds ratio; ROC, receiver operating characteristics.