Abstract 197P
Background
Approximately 75% of breast cancer patients present with Estrogen Receptor (ER) positive disease, commonly treated with ER-blocking therapies. Acquired resistance often leads to metastatic spread to the pleural cavity, resulting in a poor prognosis. At this stage, guidelines for the most-suitable treatment are lacking. Palliative treatment includes pleural fluid drainage, essential for respiratory relief. The obtained pleural fluid contains metastatic breast cancer cells, offering a valuable resource for translational research. Our study aims to use patient-derived metastatic breast cancer cells from malignant pleural effusion (MPE) as an ex vivo model to assess drug treatment response to clinically relevant compounds.
Methods
Pleural fluid from 50 patients at the Netherlands Cancer Institute was collected and immediately processed. Isolated cells were cultured for 72 hours prior to being seeded in 96-well plates and treated with various concentrations (50 umol/L- 5 nmol/L) of clinically-used systemic treatment in metastatic patients: pemetrexed, gemcitabine, docetaxel, everolimus, doxorubicin, 5-FU, carboplatin, vinorelbine, fulvestrant, ribociclib, and lapatinib. Cell viability was assessed 5 days after drug administration with the CellTiter-Glo assay.
Results
Therapy response strongly differed between patient samples, with strong cross-resistance between therapies for ER-negative cases. For ER+ MPE cultures, clear differences in therapy response were observed, with a significant association between previous endocrine therapy and drug sensitivity. Specifically, patients with a treatment history of Aromatase Inhibitors showed enhanced sensitivity to two of the tested drugs: pemetrexed and everolimus.
Conclusions
Our findings underscore the complex interplay between tumor biology, treatment history, and drug sensitivity in metastatic breast cancer. Utilizing MPE-derived cells as an ex vivo model offers valuable insights, providing information on cross-resistance or sensitivity between commonly-used therapeutics. Our data further highlight the necessity for tailored therapeutic approaches based on individual patient characteristics and prior therapy.
Legal entity responsible for the study
Zwart group.
Funding
Oncode Institute, The Mark Foundation for Cancer Research, European Union’s Horizon 2020 research and innovation programme.
Disclosure
All authors have declared no conflicts of interest.