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

Sherko Kuemmel; Hakima Harrach; Rita K Schmutzler; Athina Kostara; Katja Ziegler-Löhr; Mark H Dyson; Ouafaa Chiari; Mattea Reinisch

doi:10.1038/s41523-020-00174-9

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

NPJ Breast Cancer. 2020 Jul 24:6:31. doi: 10.1038/s41523-020-00174-9. eCollection 2020.

Authors

Sherko Kuemmel¹, Hakima Harrach¹, Rita K Schmutzler², Athina Kostara¹, Katja Ziegler-Löhr³, Mark H Dyson¹, Ouafaa Chiari¹, Mattea Reinisch¹

Affiliations

¹ Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
² Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
³ Schwerpunktpraxis für Gynäkologische Onkologie, Cologne, Germany.

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 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.

Keywords: Breast cancer; Cancer therapy.

Publication types

Case Reports