Abstract 4110
Background
Impaired DNA damage response (DDR) mechanisms and subsequent genomic instability is associated with carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. As a result, BRCA1/2 testing is recommended for a group individuals with breast/ovarian cancer.
Methods
In this study, we retrospectively invesitigated clinicopathologic features of 303 breast cancer patients tested for BRCA 1/2 mutation in an oncology institute. NCCN recommendations are used to select patients to be tested for BRCA mutations.
Results
A total of 303 patients were analysed for BRCA 1/2 mutations. Median age of the patients at diagnoses were 40 (21-65). Family history for BRCA related cancers were detected in 120 patients (39.6%). BRCA 1/2 mutations have been shown in 98 of 303 patients (32.3%). Of 98 BRCA mutated patients, 43 had pathogenic BRCA1 mutation, 39 had pathogenic BRCA2 mutation, 11 had variant of uncertain significance (VUS) BRCA2 mutation, 3 had VUS BRCA1 mutation and 2 had pathogenic BRCA1 and 2 mutations. Molecular subtypes of tumors have been shown in Table.Table:
316P Molecular subtypes of tumors
BRCA Status | HR(+)/ HER2(-), N(%) | HR(+)/ HER2(+), N(%) | HR(-)/ HER2(+), N (%) | Triple(-), N (%) | N/A,N(%) |
---|---|---|---|---|---|
BRCA1 | 18 (41.8%) | 2 (4.6%) | 0 | 22 (51.1%) | 1 (2.3%) |
BRCA2 | 25 (64.1%) | 3 (7.7%) | 0 | 6 (15.3%) | 5 (12.8%) |
BRCA1 VUS | 2 (66.7%) | 0 | 0 | 1 (33.3%) | 0 |
BRCA2 VUS | 11 (100%) | 0 | 0 | 0 | 0 |
BRCA1 + 2 | 0 | 1 (50%) | 0 | 1 (50%) | 0 |
BRCA mut (-) | 126 (61.4%) | 25 (12.1%) | 12 (5.8%) | 32 (15.6%) | 10 (4.8%) |
TOTAL | 182 (60%) | 31 (10.2%) | 12 (3.9%) | 62 (20.4%) | 16 (5.2%) |
Twelve of 98 BRCA mutated patients (12.2%) were de novo metastatic while 15 patients (15.3%) faced with metastatic disease during follow-up. In the BRCA mutated group there was significantly high rate of metastatic disease has been detected comparing BRCA non-mutated group (27.5% vs %16.5% respectively, p = 0.026). Metastatic BRCA mutant patients showed worse OS numerically but data is not statistically significant (P = 0.894). Nine patients were diagnosed with contralateral breast cancer, and 3 patients was diagnosed with BRCA-related cancers during follow-up. Prophylactic surgery (contralateral mastectomy and/or oophorectomy) was performed in 32 of 98 patients.
Conclusions
According to this retrospective study, BRCA mutant patients tend to have worse clinical and pathological features comparing age-matched controls.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sercan Aksoy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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