PM.20.031 – Towards better classification and treatment of lobular breast cancer: the European Lobular Breast Cancer Consortium (ELBCC).

Route: Personalised medicine: the individual at the centre

Cluster question: 085 Every tumour is different, so how can we come to understand cancer well enough to develop a treatment for each and every type?

Background
To personalize treatment of breast cancer patients, different classification systems have been developed for which the morphological classification is still the cornerstone. Among these morphological subtypes, invasive lobular cancer (ILC) comprises about 15% of all breast cancers.
ILC is often not palpable on physical examination, and the sensitivity on mammography is less compared to invasive ductal type cancers (IDC). Its oncogenic behavior results in a more often multicentric and bilateral mammary presence, metastases in unusual distant sites (GI tract, the meninges and the ovaries), and poor response to neo-adjuvant chemotherapy.
Furthermore, ILC is a heterogeneous disease. Most ILC express ER and PR and lack HER2, but HER2 positive and even triple negative cases occur. Molecularly, inactivation of E-cadherin is the main driver with a somatic mutation prevalence of 70%, which leads to activation of PI3K/AKT signals, regardless of somatic activating PIK3CA mutations. However, cases without E-cadherin mutations occur, which might fuel the non-classical ductolobular ILC phenotype. Until now, these molecular hallmarks of ILC have not been exploited to develop specific, ILC targeting treatment strategies.

Aim
In this multicenter consortium (AVL, Erasmus, MUMC, UMCU, LUMC, IKNL, PALGA), we will establish large, population-based, well-characterized, retrospective and prospective cohorts of ILC patients, including a biobank, to explore to what extend ILC can be considered a distinct breast cancer entity that requires a different treatment strategy than what is being offered today.
Using a combination of genetics, bioinformatics and preclinical functional tools, we will explore and develop ILC-specific treatment strategies.

Approach
-collection and analysis of 3000 ILC cases
-DNA, RNA and immunoprofiling
-Statistical, molecular, and bioinformatic data integration
-Prospective collection of ILC to establish novel preclinical modelling platforms
-Clinical trials in ILC subgroups (Dutch BOOG breast cancer study group and the European Lobular Consortium ELBCC).

Keywords

classification, Diagnosis, Lobular breast cancer, treatment

Other organisations

AVL, Erasmus Medical Center (EMC), Leiden Universitair Medisch Centrum (LUMC), Maastricht UMC, NKI

Submitter

Organisation UMC Utrecht (UMCU)
Name Prof. dr. Patrick Derksen
E-mail pderksen@umcutrecht.nl
Website www.elbcc.org