Combination Therapy with Trastuzumab and Niraparib: Quantifying Early Proliferative Alterations in HER2+ Breast Cancer Models

Ameer Mansur, Patrick N. Song, Yun Lu, Andrew C. Burns, Luke Sligh, Eddy S. Yang, Anna G. Sorace

Research output: Contribution to journalArticlepeer-review


HER2–targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical obstacle. Recently, HER2+ breast cancer cells, both resistant and responsive to HER2–targeted therapies, have demonstrated sensitivity to poly–(ADP–ribose) polymerase (PARP) inhibition, independent of DNA repair deficiencies. This study seeks to describe biological factors that precede cell viability changes in response to the combination of trastuzumab and PARP inhibition. Treatment response was evaluated in HER2+ and HER2– breast cancer cells. Further, we evaluated the utility of 3′–Deoxy–3′–[18F]–fluorothymidine positron emission tomography ([18F]FLT–PET) imaging for early response assessment in a HER2+ patient derived xenograft (PDX) model of breast cancer. In vitro, we observed decreased cell viability. In vivo, we observed decreased inhibition in tumor growth in combination therapies, compared to vehicle and monotherapy–treated cohorts. Early assessment of cellular proliferation corresponds to endpoint cell viability. Standard summary statistics of [18F]FLT uptake from PET were insensitive to early proliferative changes. Meanwhile, histogram analysis of [18F]FLT uptake indicated the potential translatability of imaging proliferation biomarkers. This study highlights the potential of combined trastuzumab and PARP inhibition in HER2+ breast cancer, while demonstrating a need for optimization of [18F]FLT–PET quantification in heterogeneous models of HER2+ breast cancer.

Original languageEnglish
Article number2090
Issue number8
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • HER2 antibody
  • PARP
  • biomarkers
  • cellular proliferation
  • molecular imaging
  • patient–derived xenograft
  • targeted therapy

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology


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