Ovarian cancer (OC) is an aggressive tumour that is usually diagnosed in an advanced stage. The presence of somatic and/or germinal mutations in the genes BRCA1 and BRCA2 is known to be predictive of response to platinum agents and inhibitors of PARP (iPARP). Nevertheless, in recent years it has been shown that the efficacy can vary according to the specific mutation. In our community there is a high prevalence of patients (pts) carrying the BRCA1 c.211 A>G germline pathogenic variant, which is a founder mutation originated in the northwest of Spain. The aim of our study was to evaluate if these pts presented different outcomes when treated with first line platinum agents.
We performed a single-centre retrospective analysis of pts carrying somatic and/or germline pathogenic variants of BRCA1 and BRCA2 treated with platinum agents and iPARP between January 2014 and December 2021. Variants were detected with validated methods in tissue and/or blood samples. Data was extracted from electronic health records and analysed with SPSS software.
We found 38 pts with the aforementioned characteristics. Median age upon diagnosis was 56.4 (range 40 – 82) years. The initial FIGO stage was IIIC in 57.9% and IV in 34.2% of the cases. The majority of pts had an ECOG PS of 1 (57.9%) or 0 (34.2%). 25 pts (65.8%) had a BRCA1 variant, and of those 12 pts carried the BRCA1 c.211 A>G variant. These pts presented a worse objective response rate (ORR) to first line platinum-based chemotherapy when compared to all the pts (58.3% vs 88.5%, p = 0.03) and to BRCA1 mutated pts (58.3% vs 84.6%, p = 0.14). Median progression free survival (PFS) to first line treatment was not significantly different among BRCA1 c.211 A>G variant carriers and the rest of the pts (27 vs 21 months, p = 0.44), and neither was overall survival (OS) (72 vs 91 m, p = 0.27).
We found that pts with BRCA1 c.211 A>G germline pathogenic variant treated in our centre had a worse response rate to platinum-based chemotherapy even thought PFS and OS were not significantly different. Further research should be carried out to test if this mutation conveys less sensitivity to DNA damaging agents.
The authors.
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All authors have declared no conflicts of interest.