Abstract 165P
Background
BRCA mutations are associated with a significant risk of breast cancer. Although there are data on the fact that different alterations in the genes can modulate this risk, they do not carry sufficient weight to modify the recommendations for follow-up or treatment, both because of the excessive fractionation of the data by specific mutations. The association by functional domains could represent an approach to the personalization of recommendations and patient follow-up, for which it is necessary to define and characterize these populations appropriately in order to look for differences between them.
Methods
We analyze 1987 germline studies performed in the Genetic Counseling Unit of the Hospital Universitario de Jaén. The domains are defined as follows: BRCA1: RING (8-96) DBD (452-1092) y BRCT (1650-1863) BRCA2: PALB2-BD (21-39) RAD51 (900-2085) y DBD (2459-3190).
Results
357 carriers were identified. 66% were female. 51.2% of BRCA1 mut. 22.4% had breast cancer, with 2 cases in males. The median age at diagnosis was 42 yr (24-76). The table shows epidemiological and clinical data of the patients, according to the affected domain. Median age at diagnosis was 42 yr in BRCA1 and 45 yr in BRCA2, with no statistically significant differences by domain. In BRCA1, 64% of luminal were BRCT-mut versus 48% of triple-negative, who showed a heterogeneous pattern in terms of mut distribution. Although a rare event, the majority of Her-2-positive patients had BRCA2 mutations (71%). As for patients with more than one tumor, ovarian cancer was detected in 7 cases, 4 due to mutations in RAD51. 8 more cases of second neoplasms were identified, 19% of the total. (Table). Table: 165P
| BRCA 1 | BRCA 2 | TOTAL | |||||||||
| RING | DBD | BRCT | Others | Total | PALB2-BD | RAD51 | DBD | Others | Total | ||
| Intrinsic subtypes | |||||||||||
| Luminal | 1 | 0 | 9 | 4 | 14 | 0 | 14 | 2 | 1 | 17 | 31 |
| TN | 2 | 2 | 14 | 11 | 29 | 0 | 5 | 1 | 2 | 8 | 37 |
| Her2 | 0 | 0 | 1 | 1 | 2 | 1 | 3 | 0 | 1 | 5 | 7 |
| Total | 3 (6.38%) | 2 (4.25%) | 25 (52.12%) | 19 (37.23%) | 49 | 1 (3.27%) | 23 (73.77 %) | 3 (9.83%) | 4 (13.11%) | 31 | 80 |
| Age at diagnosis | |||||||||||
| Media | 42.33 | 59.5 | 41.54 | 42.42 | 42.4 | 51 | 46 | 43 | 39.83 | 45 | 43 |
| Median | 38 (36-56) | 47 and 72 | 39.5 (26-68) | 45 (24-70) | 41 (24-72) | 51 | 44 (30-76) | 42 (29-60) | 41.5 (32-47) | 44 (29-76) | 42 (24-76) |
Conclusions
Characterization by functional domains can be a simple way to refine genetic counseling of patients carrying BRCA mut. There is evidence of trends towards different behaviors within each gene, although the data should be endorsed in multicenter real-life studies and yield data in less frequent mutations as well as in a wider range of tumors
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.