Optimized Modeling of Metastatic Triple-Negative Invasive Lobular Breast Carcinoma.

Date
2023-06-22ICR Author
Author
Sflomos, G
Schaumann, N
Christgen, M
Christgen, H
Bartels, S
Kreipe, H
Battista, L
Brisken, C
Type
Journal Article
Metadata
Show full item recordAbstract
Invasive lobular carcinoma (ILC) is a common breast cancer subtype that is often diagnosed at advanced stages and causes significant morbidity. Late-onset secondary tumor recurrence affects up to 30% of ILC patients, posing a therapeutic challenge if resistance to systemic therapy develops. Nonetheless, there is a lack of preclinical models for ILC, and the current models do not accurately reproduce the complete range of the disease. We created clinically relevant metastatic xenografts to address this gap by grafting the triple-negative IPH-926 cell line into mouse milk ducts. The resulting intraductal xenografts accurately recapitulate lobular carcinoma in situ (LCIS), invasive lobular carcinoma, and metastatic ILC in relevant organs. Using a panel of 15 clinical markers, we characterized the intratumoral heterogeneity of primary and metastatic lesions. Interestingly, intraductal IPH-926 xenografts express low but actionable HER2 and are not dependent on supplementation with the ovarian hormone estradiol for their growth. This model provides a valuable tool to test the efficiency of potential new ILC therapeutics, and it may help detect vulnerabilities within ILC that can be exploited for therapeutic targeting.
Collections
Subject
CDH1 mutation
HER2
LCIS
intratumoral heterogeneity
lobular breast cancer models
luminal
microenvironment
preclinical model
triple-negative breast cancer
xenograft
Research team
Endocrine control mechans
Language
eng
Date accepted
2023-06-20
License start date
2023-06-22
Citation
Cancers, 2023, 15 (13), pp. 3299 -
Publisher
MDPI