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. Confirming these findings, the team’s analysis of markers used to guide TNBC treatment showed that they vary considerably between metastatic sites and depend on the organ in which the tumor is located, suggesting that treatment decisions based on a single biopsy may not fully capture a patient’s disease.

The team is also investigating circulating tumor cells (CTCs), cancer cells found in the blood, which are easier to collect than solid tumor biopsies but far rarer and more difficult to study. The team discovered that these circulating cells differ meaningfully from those found in solid tumors, showing lower levels of key treatment-relevant markers, suggesting they may capture distinct but complementary biological information not visible in a standard tumor biopsy. 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 these findings, Dr. Desmedt’s team will expand their analysis to additional treatment targets, including newer therapies such as immunotherapies and antibody-drug conjugates. The team will also use advanced single-cell molecular techniques to better understand how CTCs reflect the disease across different organs and contribute to treatment resistance, and investigating how they resist treatment and evade the immune system to survive.