Christine Desmedt, PhD

Improving treatment for advanced triple-negative breast cancer.

Impact

Triple-negative breast cancer (TNBC) accounts for 10-15 percent of all breast cancers and typically has a worse prognosis compared to other breast cancer subtypes. Until recently, chemotherapy was the only systemic therapy option for patients with TNBC, but now targeted antibody-drug conjugates and immune checkpoint inhibitors are available to this group. Current research has demonstrated that the absence, presence, or modifications of the targets of interest for these therapies can be associated with treatment response or resistance. The biology of tumors and thus the presence of these targets can be heterogenous, or variable within individual patients and across a patient’s TNBC metastases. Knowledge is limited, however, largely because of the lack of metastatic samples. Dr. Desmedt’s research aims to refine treatment for metastatic TNBC.

Progress Thus Far

With this project, Dr. Desmedt aims to provide a comprehensive description of novel therapeutic targets in metastatic TNBC to further refine treatment in these patients. Dr. Desmedt is using a unique repository of about 500 samples of metastatic TNBC collected across three post-mortem tissue donation programs—UPTIDER (Belgium), CASCADE (Australia) and UNC Breast Tumor Donation Program (US)—to conduct three primary investigations: 1) intra-patient, inter-metastasis heterogeneity of the most relevant treatment targets; 2) the association or mutual exclusivity of the targets; and 3) the potential organ specificity of the targets. So far, the team has gathered 413 tumor samples from 21 patients. Using advanced lab techniques, they analyzed the expression of genes and proteins in the tumors that can be targeted by existing cancer treatments. Early results show that some patients had tumors that changed over time, such as gaining hormone receptor expression. They also saw that immune activity and the presence of treatment targets varied not just between patients, but also between different tumors in the same patient. By better understanding these differences, Dr. Desmedt’s goal is to improve the selection of effective, personalized treatments for patients with TNBC.

What’s Next

Building on the molecular heterogeneity observed in the tumor samples analyzed thus far, the team aims to characterize circulating tumor cells (CTCs) across multiple body fluids in patients with metastatic breast cancer (MBC). While CTC research has predominantly focused on blood, their presence in other fluids—such as ascites, pleural fluid, cerebrospinal fluid (CSF), pericardial fluid, and urine—remain underexplored. Dr. Desmedt and her team will compare breast cancer biomarkers in CTCs from various body fluids with matched solid metastases to test the possibility that CTCs confer resistance to therapy.