Multigene testing for breast cancer risk assessment: an illusion of added clinical value
The discovery of breast cancer (BC) predisposing genes, BRCA1 and BRCA2, is apparently the most impressive example of the triumph of translational medical research. BRCA1 and BRCA2 were initially identified through the linkage analysis of uniquely large cancer pedigrees, but their contribution to BC and ovarian cancer (OC) morbidity turned out to extend beyond clearly familial cancer cases: indeed, frequency of BRCA1 and BRCA2 germ-line mutations approaches close to 10% in BC and 15% in OC patients, being even higher when the affected women are selected for young age, presence of multiple tumors, specific tumor histology, etc. BRCA1 and BRCA2 play a role in cancer incidence worldwide, although significant country- and ethnicity-specific variations in frequency and spectrum of these mutations are recognized. Great efforts were invested into the estimation of BRCA1- and BRCA2-associated disease risks; based on these calculations, appropriate guidelines for BC/OC screening and prevention were formulated and subjected to clinical validation. Finally, novel drugs, which were intentionally designed to target vulnerabilities in BRCA1/2-driven cancers, recently entered clinical practice. Virtually all current standards of clinical management of healthy people and cancer patients carrying BRCA1/2 germ-line mutations rely on solid medical evidence (1-4).