Persistence of BRCA1and RAD51C methylation after neoadjuvant chemotherapy in high risk TNBC
Institution: Institute of Cancer Research
Corresponding Researcher: Stephen J Pettitt
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Summary
Methylation and silencing of the promoters of the homologous recombination repair (HRR) genes BRCA1 or RAD51C are observed in 20-30% of triple-negative breast cancer (TNBC) cases1. However, it is not known whether TNBC patients with BRCA1 or RAD51C methylation would also benefit from treatments that target defective HRR, as has been shown for patients with HRR gene mutations6. To determine the frequency of BRCA1 or RAD51C methylation in TNBC prior to neoadjuvant chemotherapy (NACT) and the degree to which this epigenetic mark is lost during therapy in those at high risk of distant recurrence due to lack of pathological complete response, we assessed promoter methylation by ampliconbased bisulphite sequencing in matched pretreatment diagnostic biopsies and postNACT residual disease (RD) samples.
