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Case Reports
. 2020 Jul 24:6:31.
doi: 10.1038/s41523-020-00174-9. eCollection 2020.

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

Sherko Kuemmel  1 , Hakima Harrach  1 , Rita K Schmutzler  2 , Athina Kostara  1 , Katja Ziegler-Löhr  3 , Mark H Dyson  1 , Ouafaa Chiari  1 , Mattea Reinisch  1
Affiliations
Case Reports

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

Sherko Kuemmel et al. NPJ Breast Cancer. .

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.

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Conflict of interest statement

Competing interestsS.K. reports receiving personal fees from Roche, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, Astra Zeneca, Somatex, MSD, Pfizer, Puma Biotechnology, PFM Medical and Lilly, and nonfinancial support from Roche, Daiichi Sankyo, Somatex and Sonoscape (outside the submitted work). A.K. reports receiving personal fees from Astra Zeneca and nonfinancial support from Tesaro and MSD (outside the submitted work). M.H.D. reports receiving personal fees from Boehringer Ingelheim, Merck, Novartis, EUSA Pharma, AbbVie, Janssen, Biogen, Menarini, and Norgine (outside the submitted work). M.R. reports receiving personal fees from Novartis, Lilly, Roche, Pfizer, Astra Zeneca, MSD and Somatex, and travel grants from Novartis, Pfizer and Celgene. Other authors report no competing interests.

Figures

Fig. 1
Fig. 1. Tumor marker response to olaparib.
Compared with pretreatment levels, there was a marked reduction in circulating CA 15–3 at 3 months after initiation of olaparib, which was deepened and sustained after 8 months of treatment.
Fig. 2
Fig. 2. Radiologic response to olaparib.
Axial (a) and coronal (b) PET/CT images acquired prior to initiation of olaparib show hypermetabolic mediastinal lymph nodes and multifocal bony attachment in the spine and pelvis. After 7 months of olaparib therapy, axial (c) and coronal (d) PET/CT images indicate significant remission of lymph node and bone metastases.
See this image and copyright information in PMC

References

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