Olaparib for metastatic breast cancer in a patient with a germline PALB2 variant.
Sherko KuemmelHakima HarrachRita K SchmutzlerAthina KostaraKatja Ziegler-LöhrMark H DysonOuafaa ChiariMattea ReinischPublished in: NPJ breast cancer (2020)
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 BRCA1/2 sequence variant affecting function. We report a patient with germline/somatic BRCA1/2 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 PALB2 (exon 1, c.18G>T, p.(=)). This case documenting activity of olaparib monotherapy in germline/somatic BRCA1/2 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.
Keyphrases
- dna repair
- metastatic breast cancer
- dna damage
- wild type
- end stage renal disease
- ejection fraction
- chronic kidney disease
- case report
- rheumatoid arthritis
- prognostic factors
- peritoneal dialysis
- stem cells
- copy number
- type diabetes
- gene expression
- randomized controlled trial
- metabolic syndrome
- climate change
- smoking cessation
- double blind