Olaparib in metastatic breast cancer accompanied by germline PALB2 mutations: 2 case reports

Introduction We present two cases with metastatic breast cancer (mBC) and germline PALB2 (gPALB2) mutation who were treated with the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib under off-label palliative settings.

Methods Case 1 experienced relapse in the mediastinal lymph node which was hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), gBRCA negative (gBRCA-), three years after initial diagnosis. Following identification of a gPALB2 mutation by next-generation sequencing (NGS), patient was initiated on olaparib, 600 mg/day (subsequently reduced to 200 mg/day). Case 2 experienced relapse in the liver which was HR+, HER2-, gBRCA-, 10 years after initial diagnosis. Following identification of a gPALB2 mutation, patient was initiated on olaparib, 600 mg/day.

Results In Case 1, substantial reduction in tumour marker CA 15-3 was evident by month 3. PET/CT scans at month 7 revealed regression of lesions corresponding to partial response (RECIST v1.1 criteria). Patient received olaparib for 16 months till disease progression after which olaparib was discontinued and patient was lost to follow-up. In Case 2, stable disease was observed for 7 months before disease progression at which point olaparib was discontinued. Case 2 died eight months thereafter.

Conclusions PARP inhibitors could have beneficial effects in mBC with gPALB2 mutations thus highlighting the need to identify this subset of patients through early NGS. Olaparib needs to be investigated in larger clinical trials on mBC patients with gPALB2 variants.

Interessenkonflikt

Hakima Harrach received travel expenses from Teva and Pfizer. Sherko Kuemmel received consulting fees from F. Hoffmann-La Roche Ltd, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, Puma Biotechnology, PFM Medical, Lilly and SonoScape; leadership roles with Westdeutsche Studiengruppe and Arbeitsgemeinschaft Gynäkologische Onkologie; research grant/funding from Somatex and Roche; travel expenses from F. Hoffmann-La Roche Ltd, Daiichi-Sankyo and SonoScape; and partial non-profit ownership of Westdeutsche Studiengruppe. Rita K Schmutzler received consulting fees from AstraZeneca, MSD, Clovis, and GSK. Christine Seiberling received travel expenses from Teva. Christine Dittmer-Grabowski received consultancy fees from AstraZeneca. Satyen Shenoy received professional fees from Abbvie, Bayer, Cantargia, Celgene, Ferring, Nestle, Sanofi, Servier, Tiburio, and Zentiva on unrelated freelance projects. Mattea Reinisch received honoraria and travel support from AstraZeneca, Celgene, Lilly, MSD, Novartis, Pfizer, Somatex, and Roche.

Publication History

Article published online:
01 June 2021