Medicina predittiva nelle pazienti con tumore della mammella: l’identificazione di varianti in geni diversi da BRCA1 e BRCA2
Predictive medicine in breast cancer patients: the identification of variants in genes other than BRCA1 and BRCA2

AUTORI

ABSTRACT

Predictive medicine in breast cancer patients: the identification of variants in genes other than BRCA1 and BRCA2

Breast cancer is the most common cancer in the female population. The majority of breast cancers are sporadic: they appear after 45 years of age, in people without other cases of cancer in their families. Only 20-30% of cases have clinical and familial characteristics that are highly suggestive of predisposition. Notably, about half of these cases are confirmed by the presence of a pathogenic variation in the BRCA genes. Patients that are carriers of these variants can benefit from highly specific prevention and medical-surgical treatment. However, BRCA genes account for only about 25% of suspected cases of genetic predisposition.
The remaining ~75% of patients, because of the absence of a confirmed genetic cause, cannot enjoy the benefits resulting from the presence of disease-genes mutation. At the same time, very often, these patients cannot be treated as sporadic tumors in the presence of a genetic predisposition phenotype. In particular, the absence of pathogenic variants in the BRCA genes has suggested the possible association of other disease-genes to breast cancer and the possibility of extending the genetic analysis to a multi-gene panel, beyond the BRCA genes. The use of multigenic panels to study genes other than BRCAs is fundamental. The greatest limitation remains the number of variants of uncertain significance that are found coupled with their clinical significance in the complexity of phenotypes. Variants in the MUTYH, FANCC and RNASEL genes were identified in a cohort of patients from Southern Italy. Therefore, it appears that the target panel approach is an effective way to identify new susceptibility genes associated with breast cancer.

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