Medicina Molecular e Genética

The Clinical Characteristics of Breast Cancers with A Familial Risk in Which No BRCA1/2 Mutations were found are Sometimes Suggestive for A Genetic Etiology

Abstract

Joris S, Shahi RB, De Brakeleer S, Fontaine C, Bonduelle M, Pauwels I, Teugels E and De Grève J

Aim: We investigated the patient and tumor characteristics of breast cancer patients with a high familial risk. The families in which the standard genetic testing revealed a BRCA1 or BRCA2 mutation were excluded to identify clinical characteristics that can be linked with an unknown genetic mutation. These characteristics were compared with those from patients in the same cohort in whom a mutation was found in BRCA1 or BRCA2 and to those from sporadic breast cancer cases (Belgian cancer registry).

Methods: The files of familial cancer cases that underwent BRCA1/2 testing between 1994 and 2012 were retrospectively analyzed.

Results: The BRCA1 related breast cancers occur at a median age of 42, BRCA2 at a median age of 44, familial non-BRCA1/2 at a median age of 47 and sporadic breast cancer at the age of 63. The lower median age of incidence in the non-BRCA1/2 group compared to the sporadic breast cancer group makes use conclude that there are probably moderate risk genes involved. Generational anticipation was also observed in some of the BRCA1/2 negative families. We did not find any significant differences in the pathological characteristics of breast cancers occurring in BRCA1/2 negative patients with a high familial risk compared to sporadic cases.

Conclusion: A shift towards a younger age of disease incidence and “anticipation” in some families suggests the involvement of a genetic factor. The identification of other genetic causes in these familial cases is therefore warranted.