Optimized Modeling of Metastatic Triple-Negative Invasive Lobular Breast Carcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Jul 14

PMID 37444409

Authors

George Sflomos

Nora Schaumann

Matthias Christgen

Henriette Christgen

Stephan Bartels

Hans Kreipe

Laura Battista

Cathrin Brisken

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Glucocorticoid Receptor Activation in Lobular Breast Cancer Is Associated with Reduced Cell Proliferation and Promotion of Metastases.

Porter B, Frerich C, Laine M, Clark A, Durdana I, Lee J Cancers (Basel). 2023; 15(19).

PMID: 37835373 PMC: 10571671. DOI: 10.3390/cancers15194679.

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