Assessement of Potential Interest of [68Ga]Ga-PentixaFor PET/CT in Metastatic Triple Negative Breast Cancer Patients

Overview

Triple-negative breast cancer (TNBC) is a particularly aggressive type of breast cancer that is difficult to treat. Unlike other forms of breast cancer, TNBC tends to relapse earlier and spread more quickly to other parts of the body. Unfortunately, patients with TNBC have a lower survival rate, often less than five years after diagnosis. This highlights the urgent need for better treatments for TNBC. One of the main challenges in treating TNBC is that it lacks certain receptors that other breast cancers have. These receptors are usually targeted by specific therapies, making TNBC harder to treat with targeted approaches. Currently, a type of imaging called \[18F\]FDG PET/CT is the most accurate method for detecting breast cancer and its spread. However, with the rise of personalized medicine, there is a growing interest in molecular targeted approaches. These methods aim to provide highly specific diagnostics and treatments based on the unique characteristics of each patient's cancer. One promising target for these new approaches is a receptor called CXCR4. CXCR4 is found on the surface of many cells and is involved in various processes in the body. It is often overexpressed in different types of cancer, including breast cancer. Research has shown that CXCR4 levels are higher in metastatic sites (where cancer has spread) compared to primary tumors. CXCR4 is not only present in cancer cells but also in immune cells within the tumor environment. In invasive breast cancer, CXCR4 plays a crucial role in tumor migration, invasiveness, metastasis, and proliferation. A clinical study evaluated 18 breast cancer patients using a new imaging method called \[68Ga\]Ga-PentixaFor PET/CT or PET/MR. They found that this method showed higher uptake in breast cancer cases with poorer prognosis compared to the traditional \[18F\]FDG PET/CT. Higher CXCR4 expression is particularly seen in TNBC compared to other breast cancer subtypes. The goal of the study is to assess how \[68Ga\]Ga-PentixaFor is distributed in the body using PET/CT imaging. This will help demonstrate the potential of CXCR4 as a promising target for new treatments. If successful, \[68Ga\]Ga-PentixaFor PET/CT could become a valuable tool for identifying patients who might benefit from treatments using \[177Lu\]/\[90Y\] PentixaTher.

Triple-negative breast cancer (TNBC) is the most aggressive and hard-to-treat form of breast cancer. TNBC has a higher propensity for earlier relapse and an increased risk of metastasis than all other forms of breast cancer. TNBC patients have a low survival rate (\<5 years). This clearly shows an urgent unmet medical need for TNBC patients. The lack of receptors makes it challenging to develop more effective targeted therapy to treat TNBC. Currently, \[18F\]FDG PET/CT offer highest diagnostic accuracy in the detection of breast cancer and distant metastases. With the increasing role of personalized medicine, however, the desire for molecular targeted approaches emerged, enabling high-specificity diagnostics and molecular targeted therapies with the appropriate molecular key target. CXCR4 is a 7-transmembrane G-coupled receptor belonging to the chemokine receptor family and is expressed by a variety of cells during development and thereafter. CXCR4 has been found to be overexpressed by various human cancers including breast cancer. The level of CXCR4 expression was shown to be higher in metastatic sites as compared to the primary tumours, and changes in CXCR4 signalling have been shown to significantly alter metastatic burden in animal models. CXCR4 is not only expressed by cancer cells themselves, but also by tumour-infiltrating immune cells. Within the tumour microenvironment, the major CXCR4-expressing cells are B-lymphocytes and plasmacytoid dendritic cells, both potentially contributing to an immunosuppressive site permissive for tumour progression. CXCR4 is frequently overexpressed in invasive breast cancer and has an important role in tumour migration, invasiveness, metastasis, and proliferation (2). Vag et al. evaluated 18 patients with breast cancer who underwent \[68Ga\]Ga-PentixaFor PET/CT or PET/MR (6). It was noted that a higher SUVmax of \[18F\]FDG was observed in all cases, compared with \[68Ga\]Ga-PentixaFor. It was also noted that the uptake seen in breast cancer is associated with a poorer prognosis. Higher CXCR4 expression is seen in triple-negative breast cancer compared to the luminal subtypes. \[68Ga\]Ga-PentixaFor PET/CT may have a role in prognostication of breast cancer. The purpose of this trial is to assess the biodistribution of \[68Ga\]Ga-PentixaFor using PET/CT imaging, thus allowing us to demonstrate the potential of CXCR4 as a promising molecular target. After establishing the targeting properties of \[68Ga\]Ga-PentixaFor PET/CT in TNBC, it could act as an effective companion imaging diagnostic and therefore a useful tool for identification of patients potentially benefiting from treatment using the theragnostic equivalent \[177Lu\]/\[90Y\] PentixaTher.