SUMMARY

Life-saving, risk-reducing medical interventions are required for women with a BRCA1/2 mutation. Interventions comprise a four-stage approach that involves risk assessment, genetic counseling, gene-mutation analysis and medical intervention strategies. Genetic counseling should be offered at specialized familial breast-cancer clinics and gene-mutation analysis should be recommended on the basis of personal and family-history-based risk criteria. Prophylactic bilateral salpingo-oophorectomy appears to offer the optimal benefit–risk ratio compared with prophylactic bilateral mastectomy, chemoprevention, or intensified surveillance. Tamoxifen is an alternative approach only for BRCA2 mutation carriers. The comprehensive, clinical decision-making Ioannina algorithm provided here can facilitate the complex preventive strategic approach. Newly diagnosed BRCA1/2 carriers might bene-fit from extensive surgery and a specific pharmacological treatment, but data to support this strategy are limited. Microarray gene-expression studies show that breast tumors from BRCA1 carriers are predominantly of basal subtype (i.e. triple negative) and BRCA2 carriers are of luminal subtype (i.e. estrogen-receptor-positive). Although optimum management of women with familial susceptibility to breast and ovarian cancer has not yet been prospectively validated, data indicate substantial benefits when an individualized evidence-based prevention strategy is provided by an experienced team.