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

Jacopo Berrino, Franco Berrino, Silvia Francisci, Bernard Peissel, Jacopo Azzollini, Valeria Pensotti, Paolo Radice, Patrizia Pasanisi, Siranoush Manoukian

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)117-128
Number of pages12
JournalFamilial Cancer
Issue number1
Publication statusPublished - Nov 6 2014


  • BRCA genes
  • Breast cancer
  • Mutation probability
  • Ovarian cancer
  • Penetrance
  • Risk estimation model

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)
  • Medicine(all)


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