Atlas of Lobular Breast Cancer Models: Challenges and Strategic Directions

Abstract

Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancer (BC) cases and responds well to endocrine treatment when estrogen receptor α-positive (ER+) yet differs in many biological aspects from other ER+ BC subtypes. Up to 30% of patients with ILC will develop late-onset metastatic disease up to ten years after initial tumor diagnosis and may experience failure of systemic therapy. Unfortunately, preclinical models to study ILC progression and predict the efficacy of novel therapeutics are scarce. Here, we review the current advances in ILC modeling, including cell lines and organotypic models, genetically engineered mouse models, and patient-derived xenografts. We also underscore four critical challenges that can be addressed using ILC models: drug resistance, lobular tumor microenvironment, tumor dormancy, and metastasis. Finally, we highlight the advantages of shared experimental ILC resources and provide essential considerations from the perspective of the European Lobular Breast Cancer Consortium (ELBCC), which is devoted to better understanding and translating the molecular cues that underpin ILC to clinical diagnosis and intervention. This review will guide investigators who are considering the implementation of ILC models in their research programs.

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer

“…66 Altogether, the molecular features of ILC are being slowly uncovered during the past decade, mainly thanks to the increasing number of human ILC samples and models that are becoming available. 67 CLINICAL IMAGING…”

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial

“…Previous data indicate synergy between platinum compounds and ICB in genetically engineered mouse models for ILC 18 . Of note, while these models strongly resemble human ILC, the field traditionally lacks models for endocrine-sensitive ILC 19 , 20 . Additionally, immune-related ILCs, characterized by the expression of immune-related genes, were responsive to DNA-damaging agents, such as platinum, in vitro 11 .…”

In vitro breast cancer models for studying mechanisms of resistance to endocrine therapy

“…PDOs as a translational tool have revolutionized the study of breast cancer and therapy response tailored to the individual [ 59 ]. PDOs recapitulate the histological and genetic status of the original tumor, largely because the PDO models are cultured relatively short-term and in the presence of a serum-free culture medium compared to cell line models [ 60 ].…”