Durable Disease-free Survival in a Patient with Metastatic Triple-negative Breast Cancer Treated with Olaparib Monotherapy

Abstract

Background: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and few effective targeted therapy options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been granted accelerated approval by FDA for patients with deleterious BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer. However, there is little data demonstrating that patients with particular forms of germline and/or somatic BRCA1/2, such as large fragment variation, can benefit from PARP inhibitors. Case Presentation: In 2011, a 40-year-old woman was diagnosed with TNBC having pT2N0M0 in the right breast, and a new irregular lesser tubercle in the left breast appeared after approximately 3 years, which was also diagnosed as TNBC. In 2017, computed tomography (CT) showed TNBC metastases to the lung and brain. A next-generation sequencing (NGS) was performed with a lung metastasis sample, and results showed a homologous recombination deficiency (HRD) score of 67, a germline large deletion of exon 2 in BRCA1, a novel somatic BRCA2-STARD13 rearrangement and copy number loss of RAD51. Since September 2017, the patient was treated with olaparib. Till the report date of this case, the patient underwent regular follow-up without disease recurrence. Conclusion: To our knowledge, this is the first case describing a patient with lung- and brainmetastatic TNBC with combined germline and somatic large rearrangement and a high HRD score who achieved a long-term benefit from olaparib monotherapy. The use of NGS is promising in the treatment of TNBC in clinical practice.