Triple-negative breast cancer (TNBC) usually shows defects in homologous recombination (HR) DNA repair, frequently due to germline mutations in BRCA1 and BRCA2 genes or other somatic mutations affecting genes involved in HR.
Two studies have recently shown at the ESMO Breast Cancer Virtual Congress 2021 that homologous repair deficiency (HRD), defined by a low RAD51 score, could be used as biomarker for response to PARP inhibitors or carboplatin in triple negative breast cancer (TNBC).
To evaluate this hypothesis, the researchers developed an immunofluorescence-based assay to determine the percentage of RAD51 foci in tumour samples from treatment-naïve patients with TNBC. The RAD51 test (RAD51-IF) was conducted before (baseline) and at the end of treatment (EoT) with rucaparib, a PARP inhibitor. For comparison, current genetic and genomic test that measure HRD were also conducted. The study showed that baseline low RAD51 (predefined as low if ≤10%) was associated with functional HRD and sensitivity to PARPi.
Similarly, a second study demonstrated that patients with low RAD51 benefited from the addition of carboplatin to neoadjuvant chemotherapy in TNBC. In this study, the RAD51 test was shown to be in concordance with the tumour BRCA status: RAD51 score identified 93% of BRCA-mutated tumours. Additionally, there was also a high concordance for RAD51 score with the genomic HRD score (myChoice® CDx).
Altogether, these results support the idea that addition of RAD51 testing into clinical practice would help in clinical decision making.
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References
[1] Serra Elizalde V, Llop-Guevara A, Pearson A, et al. Detection of homologous recombination repair deficiency (HRD) in treatment-naive early triple negative breast cancer (TNBC) by RAD51 foci and comparison with DNA-based tests. ESMO Breast Cancer Virtual Congress 2021 (5-8 May).
[2] Llop-Guevara A, Vladimirova V, Schneeweiss A, et al. Association of RAD51 with Homologous Recombination Deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial. ESMO Breast Cancer Virtual Congress 2021 (5-8 May).
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