Disease Extent in Stage IV Lobular Carcinoma: the Aid of Imaging and Liquid Biopsy Analyses

Metastatic invasive lobular carcinoma (ILC) is a distinct breast cancer subtype characterized by loss of E-cadherin and a diffuse growth pattern that makes metastases difficult to detect with standard imaging such as computed tomography (CT) or 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET)/CT. As a result, disease burden in patients with ILC is frequently underestimated, progression is identified later than clinically optimal, and many patients are excluded from clinical trials due to insufficiently measurable disease. Whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) is a radiation-free imaging technique that has demonstrated improved sensitivity for detecting metastases-including peritoneal, bone, and nodal disease-in ILC. Retrospective studies suggest that WB-DWI/MRI can identify clinically relevant progression not visible on standard imaging. However, prospective evidence in ILC is lacking. Circulating tumor DNA (ctDNA) has also shown promise as a minimally invasive biomarker for monitoring treatment response, with early molecular changes often preceding radiologic progression, but data specific to ILC remain limited. The DELILA study is a prospective, multicenter clinical trial conducted at University Hospitals Leuven and Institut Jules Bordet. The study aims to enroll 43 patients starting first-line systemic therapy for metastatic hormone receptor positive human epidermal growth factor receptor 2 negative (HR+/HER2-) ILC. Participants undergo serial dual imaging-WB-DWI/MRI and standard-of-care imaging-at baseline, at 1 month, and approximately every 3 months for up to 30 months or until disease progression. At each imaging time point, blood samples are collected for ctDNA analysis and Ca15.3 tumor marker assessment. Patient-reported psychological burden related to repeated imaging and blood sampling is evaluated using validated questionnaires. The primary objective is to assess the added value of WB-DWI/MRI in detecti