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

Sherko Kuemmel1, Hakima Harrach1, Rita K Schmutzler2

  • 1Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany.

NPJ Breast Cancer
|July 31, 2020
PubMed

Insights

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors show promise for metastatic breast cancer (MBC) patients beyond current BRCA approvals. A BRCA wild-type MBC patient with a PALB2 variant responded dramatically to olaparib, suggesting broader PARP inhibitor utility.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Current poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor approvals for metastatic breast cancer (MBC) require germline BRCA1/2 sequence variants.
  • There is a biologic rationale for expanding PARP inhibitor use to a wider MBC patient population.

Observation:

  • A 37-year-old woman with recurrent, hormone receptor-positive, HER2-negative MBC, wild-type for germline/somatic BRCA1/2, progressed on standard therapies.
  • The patient received the PARP inhibitor olaparib.

Findings:

  • The patient experienced a dramatic and sustained response to olaparib monotherapy lasting at least 8 months.
  • Sensitivity to olaparib was likely due to a germline PALB2 sequence variant (exon 1, c.18G>T, p.(=)) affecting homologous recombination repair.

Implications:

  • This case demonstrates the clinical activity of olaparib in metastatic breast cancer patients who are wild-type for BRCA1/2.
  • PARP inhibition may benefit MBC patients with other genetic alterations impacting homologous recombination repair, extending beyond current indications.
Keywords:
Breast cancerCancer therapy

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