Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability

Fam Cancer. 2015 Mar;14(1):117-28. doi: 10.1007/s10689-014-9766-8.

Abstract

We have designed the user-friendly COS software with the intent to improve estimation of the probability of a family carrying a deleterious BRCA gene mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO software, but it incorporates improved assumptions on cancer incidence in women with and without a deleterious mutation, takes into account relatives up to the fourth degree and allows researchers to consider an hypothetical third gene or a polygenic model of inheritance. Since breast cancer incidence and penetrance increase over generations, we estimated birth-cohort-specific incidence and penetrance curves. We estimated breast and ovarian cancer penetrance in 384 BRCA1 and 229 BRCA2 mutated families. We tested the COS performance in 436 Italian breast/ovarian cancer families including 79 with BRCA1 and 27 with BRCA2 mutations. The area under receiver operator curve (AUROC) was 84.4 %. The best probability threshold for offering the test was 22.9 %, with sensitivity 80.2 % and specificity 80.3 %. Notwithstanding very different assumptions, COS results were similar to BRCAPRO v6.0.

MeSH terms

  • Area Under Curve
  • Bayes Theorem
  • Breast Neoplasms / genetics
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Penetrance
  • ROC Curve
  • Software*

Supplementary concepts

  • Breast Cancer, Familial