Dissimilarity between sporadic, non-BRCA1/2 families and hereditary breast cancer, linked to BRCA genes, in the Tunisian population.

Background: Most breast cancers (90 %) are sporadic. Only 5-10 % of all cancer cases can be attributed to genetic defects. BRCA genes are strongly incriminated in the hereditary predisposition to the disease. The purpose of our study was to provide more efficient approach to identify pathogenic BRCA mutation carriers and to determine subgroups within the non-BRCA tumor class.

Methods: Different clinicopathological features, reproductive factors, as well as psychosocial ones were compared in women carrying mutations in the BRCA1/BRCA2 genes (12 cases) with non-BRCA1/2 family tumors (36 cases) and age-matched sporadic cases, unselected for family history (44 cases).

Results: A BRCA-related class was yielded based on age at diagnosis (age ≤ 35 years; p = 0.1), molecular subtypes(the triple-negative subtype was predominant: 43 % of cases; p = 0.025) and age at menarche (p = 0.04). Furthermore, a "probably sporadic" class was distinguished using hormonal contraceptive use (through 30-40 years of age; p = 0.039), the number of full-term pregnancies (age ≥40 years; p = 0.01), age at menopause(age > 50 years; p = 0.04) and psychosocial factors (age ≥ 40 years; p = 0.01). However, analysis of non-BRCA1/2 family tumors indicated that they constitute a heterogeneous class, showing few perceptible differences with sporadic group, but distinct from BRCA1/2 tumors.

Conclusions: In Tunisian population, breast cancer can be classified with a high level of accuracy as sporadic or related to BRCA germline mutations by combining different clinicopathological features and reproductive factors. This can be clinically useful in genetic counseling and decision making for BRCA genetic test.