Invasive Lobular Carcinoma (ILC)

Invasive Lobular Carcinoma (ILC)

Invasive lobular carcinoma (ILC) is the most common "special" histological subtype of invasive breast cancer, accounting for up to 15% of all cases. At Alfa Cytology, our team of experienced biologists work with you to develop ILC therapeutics.

Introduction to Invasive Lobular Carcinoma (ILC)

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer diagnosed in the U.S., accounting for 10 to 15 percent of all invasive breast cancers diagnosed. ILC is notable for its distinct lack of E-cadherin function, which underlies the characteristic discohesive growth pattern observed, with individual tumor cells arranged in a single-file infiltrative manner and dispersed throughout the surrounding stroma. Typically, ILCs are of the luminal molecular subtype, expressing estrogen and progesterone receptors while lacking HER2 overexpression.

Fig.1 ILC subtypes by IHC. (McCart Reed, A.E., et al., 2021)Fig.1 ILC subtypes by IHC. (McCart Reed, A.E., et al., 2021)

Ongoing Clinical Trials in Invasive Lobular Carcinoma (ILC)

ILC is now recognized as a distinct disease process, and there is growing clinical evidence that a one-size-fits-all approach for all invasive breast cancers is not appropriate for specific subtypes such as ILC. As a result, a number of clinical trials have emerged to investigate ways to improve the therapeutic management of ILC.

NCT Category Therapeutics Phase
NCT02206984 Endocrine Therapy Tamoxifen + Anastrozole + Fulvestrant
NCT02764541 Cyclin-dependent Kinase Inhibitors + Endocrine Therapy Letrozole + Tamoxifen + Palbociclib + Endocrine Therapy
NCT03113825 E-cadherin/ROS1 Inhibitor Crizotinib + Fulvestrant
NCT04551495 Combination Therapy Tyrosine Kinase Inhibitor + Letrozole + Goserelin

Our Services

At Alfa Cytology, we pride ourselves on our comprehensive suite of preclinical services tailored to the unique needs of ILC research. Our state-of-the-art facilities and highly trained personnel enable us to provide cutting-edge in vitro and in vivo models, as well as advanced imaging and molecular analyses, to support the development of innovative ILC therapies.

Animal Models of Invasive Lobular Carcinoma

Xenograft Model Development

Genetic Engineering Model Development

Optional Cell Lines: SUM-44 PE, MDA-MB-134-VI, IPH-926, T69, T73, T78, LA-PDX1, BCM-3561, HCI-005, Others. Optional Transgene: Trps1, Cdh1, Tp53, Pten, AKT, Myh9, t-ASPP2, Others.
Optional inoculation routes: systemic, local, orthotopic, subcutaneous, and intraductal injections. Optional Species: Mouse, Rat, Dog, Zebrafish, Others.

Case Study

An Intraductal ILC Xenograft Model for Assessing the Therapeutic Potential of Compound A as a Selective LOX Inhibitor

  • Model Introduction

The intraductal invasive lobular carcinoma (ILC) xenograft model is a specialized preclinical platform for studying estrogen receptor-positive ILC, a distinct breast cancer subtype characterized by E-cadherin loss, unique metastatic patterns, and unpredictable treatment responses. This model effectively recapitulates key pathological features of human ILC and provides a relevant system for evaluating novel therapeutic agents targeting this challenging disease.

  • Model Information
  • Model: Intraductal Invasive Lobular Carcinoma (ILC) Xenograft Model
  • Cancer Type: Invasive Lobular Carcinoma (Estrogen Receptor-Positive)
  • Host Mouse Strain: Severe Immunodeficient Mice
  • Age: 6-8 Weeks
  • Cell Line Origin: MDA-MB-134 (derived from ILC metastasis)
  • Molecular Profile: E-cadherin loss; Estrogen receptor-positive
  • Weight: 18-22 g
  • Model Construction

The ILC xenograft model was established by implanting sustained-release estrogen pellets subcutaneously into severe immunodeficient mice to support the growth of estrogen receptor-positive tumors. The ILC-derived metastatic cell line (MDA-MB-134) was then directly inoculated into the mammary fat pads of mice via intraductal transplantation.

Fig. 2 Schematic diagram of the construction of the intraductal ILC xenograft model. (Source: Alfa Cytology)

  • In Vivo Efficacy Evaluation

This case utilized the established intraductal ILC xenograft model to systematically evaluate the anti-tumor efficacy of candidate compound A as a selective LOX inhibitor.

  • Effective Tumor Growth Inhibition: Both the dual LOX/LOXL1 inhibitor (Compound A) and the specific LOXL1 inhibitor (Compound B) significantly suppressed primary tumor growth in the orthotopic breast cancer model, reducing tumor volume by approximately 75% and 55% respectively, confirming its potent anti-tumor activity (Fig. 2).

Fig. 3 In vivo targeting of LOX can delay tumor growth and reduce tumor burden. (A) Treatment of mouse orthotopic MDA-MB-134 human breast cancer with compound A and (B) compound B can significantly delay tumor growth and reduce tumor burden. (Source: Alfa Cytology)

To learn more about our expertise in ILC research or to discuss potential collaborations, please don't hesitate to contact us at Alfa Cytology. We are committed to advancing the understanding and treatment of this important breast cancer subtype, and we welcome the opportunity to work with you in pursuit of this goal.

References

  1. McCart Reed, A.E., Kalinowski, L., and et al. Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Res. 2021, 23, 6. 
  2. Mouabbi J A, Hassan A, and et al. Invasive lobular carcinoma: an understudied emergent subtype of breast cancer. Breast cancer research and treatment. 2022, 193(2): 253-264.
All our services are exclusively intended for preclinical research purposes. They are not intended for diagnostic, therapeutic, or patient management applications.