BRCA1/2 testing can guide therapy in Ovarian Cancer

Homologous recombination repair (#HRR) pathway repairs double-strand DNA breaks, and its deficiency leads to Homologous recombination deficiency (#HRD), resulting in genomic instability and contributing to cancer.
HRD mutations, including #BRCA1 or #BRCA2 mutations are important actionable biomarkers in #Ovariancancer, that are sensitive to #PARP inhibitors that block the repair of #DNAdamage, such as #olaparib, #rucaparib, and #niraparib.

Patients with mutations in BRCA1/2 account for ~15% (range 7%–21%) of ovarian cancers. Several phase-III double blind, randomized trials have shown that patients with advanced ovarian cancer carrying BRCA1/2 mutations have better progression-free survival (PFS) with PARP inhibitors compared to placebo (SOLO-1 trial Olaparib, PAOLA-1 trial Olaparib + Bevacizumab, PRIMA trial Niraparib)

We sequenced 89 of our 1100+ Ovarian cancer resection cases using a 43-gene HRR #NGS panel, which identified several mutations in genes involved in HR pathway, such as TP53, BRCA1, ARID1A, BRCA2, PTEN, ATR and ATM. We identified pathogenic/likely pathogenic BRCA1/2 #missense and #truncated mutations (see figure below) that result in the loss of BRCA1/2 tumor suppressor function. These oncogenic alterations may predict response to PARP inhibitors and guide choice of therapy.