Mexican women with ovarian cancer have a high prevalence of germline BRCA mutations. The most frequent alteration is the deletion of exons 9 to 12 of BRCA1 (BRCA1-Del Exon 9-12), which has been associated with a founder effect in this population. The Mexican founder mutation is a long genomic rearrangement that could affect not only clinical features but also the prognosis of patients carrying this alteration.
This retrospective study evaluated the clinical characteristics and prognosis of Mexican patients with BRCA1/2 germline mutations after receiving first line treatment with platinum-based chemotherapy between 2015 and 2022. The aim of the study was to compare the progression-free survival (PFS) of patients with the Mexican founder mutation and patients with other BRCA1/2 mutations. Patients treated with front-line iPARP maintenance treatment were excluded.
Of 531 patients who were tested for a BRCA1/2 mutation, 181 were positive (34.1%). Thirty-seven patients (20.4%) were Mexican founder mutation carriers and 144 (79.6%) had other BRCA1/2 mutations. One hundred fifty-seven patients were included in the final survival analysis. The median follow-up time was 57 months. Patients with the founder mutation had a median PFS of 28.7 months, while patients with other BRCA1/2 mutations had a median PFS of 15.3 months (HR, 0.72; CI 95% 0.46 – 0.95; P= 0.05). (Table 1) Median overall survival was not reached for patients with the founder mutation and 131 months for patients with other BRCA1/2 mutations (HR 0.25; CI 95% 0.0.88 – 0.72; P=0.01).
| Table 1. Survival analysis | |||
| n | Median (CI 95%) | P | |
| PFS | |||
| Total | 157 | 17.28 (14.06 - 20.49) | |
| Mutation type | 0.05 | ||
| Mexican founder mutation | 32 | 28.74 (15.10 - 42.38) | |
| Other BRCA1/2 mutations | 125 | 15.31 (12.59 - 18.02) | |
| BRCA mutation type | 0.32 | ||
| BRCA1 | 84 | 14.91 (11.88 - 17.94) | |
| BRCA2 | 41 | 16.75 (11.77 - 21.73) | |
| Mexican founder mutation | 32 | 28.74 (15.10 - 42.38) | |
| OS | |||
| Total | 157 | 137.46 (103.21 - 171.70) | |
| Mutation type | 0.010 | ||
| Mexican founder mutation | 32 | NR (NR - NR) | |
| Other BRCA1/2 mutations | 125 | 131 (90.47 - 172.49) | |
| BRCA mutation type | 0.013 | ||
| BRCA1 | 84 | 109.60 (65 - 154.20) | |
| BRCA2 | 41 | NR (NR - NR) | |
| Mexican founder mutation | 32 | NR (NR - NR) | |
Patients with the Mexican founder BRCA1 mutation treated with first line platinum-based chemotherapy have better survival compared with patients with other BRCA1/2 mutations.