Introduction:

Invasive lobular carcinoma (ILC) has long been recognized as a histological breast cancer subtype based on its peculiar phenotypical features, mainly composed of discohesive cells. However, the disease has only started to be appreciated as a specific clinical entity in the last decade. Preceding this, it had become evident that ILC distinguished itself from all other breast cancer subtypes, based on mRNA expression profiles and a predisposition towards inactivation of E-cadherin (CDH1). In recent years, next generation and consortium-led genomic sequencing efforts have substantiated the unique character of ILC, through the identification of ILC-specific (driver) mutations. The current ultimate challenge is the validation and translation of these findings into an improved diagnosis and treatment, and their implementation into daily clinical practice.

WG1: Guidelines for harmonized pathological and imaging diagnosis of ILC

Leader: Matthias Christgen Ph.D.

Co-leader: Anne Salomon Ph.D.

Summary: Here we aim at standardizing and increasing the reproducibility of pathological diagnosis of ILC, harmonizing the clinical management of ILC patients at initial diagnosis, improving and tailoring treatment decisions (surgical, adjuvant, neoadjuvant and metastatic settings) and defining the optimal follow -up practices post-treatment.

WG2: Prospective ILC collection, biobanking, data storage and sharing

Leader: Maria Brito Ph.D.

Co-leader: Marion Maetens Ph.D.

Summary: Here we will focus on the collection of patient material, the accompanying data and centralized storage to provide a comprehensive collection of ILC. Patient material includes samples from the primary tumor, the involved axillary lymph nodes, adjacent normal mammary tissue, metastatic material, as well as blood samples. We will be a collective effort of clinicians, pathologists, OMICs experts and data/server managers, managed by the WG leader and MC team.

WG3: OMICS approaches to define and stratify ILC

Leader: Prof. Darran O’Conner Ph.D.

Co-leader: Francois Richard Ph.D.

Summary: Here we aim to provide multi-level molecular characterization of ILC using state-of-the -art OMICs technologies to identify predictive and prognostic biomarkers for ILC. The outcome of this WG will directly feed into WG1 to improve differential diagnosis and stratification of patient cohorts, and provide candidates for functional studies as depicted in WG4. This Action will ensure rapid dissemination of the molecular findings to both basic scientists and clinical doctors to improve the translational from bench to bedside.

WG4: ILC Model Systems: Mouse modelling, Biochemistry, Genetics, Functional Cell Biology

Leader: Georgios Sflomos Ph.D.

Co-leader: Val Bruntun Ph.D. / Clare Isacke Ph.D.

Summary: Here we aim to advance the knowledge on ILC biology and biological responses based on functional biomarkers. Biomarkers will be deduced from existing literature, WG4, and functional intervention screens in this WG. The Action will also focus on PDO and PDX development from metastatic sites (pleural effusions, ascites, leptomeningeal sites) to generate unique tools for functional studies. Secondly, this WP will focus on In Vitro functional analyses. Specifically, single cell mRNA analyses will be done on PDOs to identify ILC heterogeneity and the underlying drivers. In parallel, proteomics will define protein expression and post-translational modifications that promote the oncogenic features of ILC. Proximal extracellular cues will be studied using biophysical experiments.

WG5: ILC-specific clinical trial design

Leader: Prof. Elinor Sawyer Ph.D.

Co-leader: Elsbieta Senkus Ph.D. / Marleen Kok Ph.D. 

Summary: Here we will use diagnostic parameters from WG1 and WG3 (histology and clinical biomarkers), supported by the deliverables from WG4 (functional biomarkers) to better define ILC, identify promising prognostic and predictive markers, and therapeutic targets. It will further stratify patient cohorts based on improved guidelines from WG1 and define inclusion criteria for future clinical intervention trials.