Olaparib for metastatic breast cancer in a patient with a germline PALB2 variant

Abstract

There is a strong biologic rationale that poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors may benefit a broader range of metastatic breast cancer (MBC) patients than covered by current approvals, which require a germline <i>BRCA1/2</i> sequence variant affecting function. We report a patient with germline/somatic <i>BRCA1/2</i> wild-type MBC, who had a dramatic response to the PARP inhibitor olaparib of at least 8 months' duration. The patient is a 37-year-old woman with recurrent, hormone receptor-positive, HER2-negative MBC that had progressed despite hormonal therapy and palbociclib. Sensitivity to olaparib was likely conferred by a germline sequence variant affecting function in <i>PALB2</i> (exon 1, c.18G>T, p.(=)). This case documenting activity of olaparib monotherapy in germline/somatic <i>BRCA1/2</i> wild-type MBC illustrates that the clinical potential of PARP inhibition in MBC extends beyond currently approved indications to additional patients whose tumors have (epi)genetic changes affecting homologous recombination repair.