Letters Section Editor: Robert M. Golub, MD, Senior Editor.
In Reply: Dr Iversen and colleagues recognize the important effect of family structure on BRCA mutation prediction. We agree that BRCAPRO is probably the most robust of the models commonly used in genetic cancer risk assessment clinics.1 Our article noted that the mendelian construction of BRCAPRO should allow it to account for family characteristics, such as the presence or absence of unaffected relatives, if its parameters are correctly specified. Our data, whether or not an artifact of our specific cohort, call into question those parameters. Among the women with identified BRCA mutations, 16 of 29 (55%) had a BRCAPRO probability of less than 5%, significantly less than the 10% threshold commonly used for offering BRCA testing (Table).1,2 Family structure was limited in 11 of 16 (69%) of those cases. Although it is correct that the number of carriers identified was within 1 SD of the BRCAPRO estimates, clinicians may use only the single point estimate in determining whether a given woman exceeds a specified threshold for BRCA testing.
Weitzel JN, Lagos VI, MacDonald DJ. Limited Family Structure and Breast Cancer Risk—Reply. JAMA. 2007;298(17):2007–2008. doi:10.1001/jama.298.17.2007-b