Case report: Response to platinum agents and poly (adenosine diphosphate-ribose) polymerase inhibitor in a patient with BRCA1 c.5096G>A (R1699Q) intermediate-risk variant

Background: BRCA1 c.5096G>A (p. Arg1699Gln) (hereinafter BRCA1 R1699Q) is classified as a pathogenic genetic variant despite its lower penetrance of breast and ovarian cancers compared to other BRCA1 variants. However, this mutation is currently reported as a 'special interpretation' variant in the BRACAnalysis® because the response to platinum agents and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors remains unknown in patients with this mutation. Case presentation: We present a case of stage IIIc high-grade primary peritoneal cancer in a 69-year-old woman with germline BRCA1 R1699Q variant. She received platinum-containing chemotherapy followed by surgery. Eight months later, the patient experienced recurrence and received six cycles of chemotherapy and olaparib maintenance therapy. However, the disease progressed after only 5 months, and she received another chemotherapy drug. This patient responded slightly to platinum agents and had shorter progression-free survival on olaparib compared with clinical trial data. myChoice® CDx also showed Genomic Instability Score (GIS) was 50. This patient had no other gene mutations which could cause homologous recombination deficiency. Conclusion: This is the first report of the clinical outcome of PARP inhibitor and platinum-containing chemotherapy in a patient with a BRCA1 R1699Q variant. Despite BRCA1 mutation and high GIS, used as indicators of drug sensitivity, the recurrent tumor did not respond well to platinum agents and olaparib. BRCA1 R1699Q variant could differ from others in cancer risk and in drug response. Further studies are needed to confirm these observations.