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Updated: Nov 24, 2025
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Modeling molecular development of breast cancer in canine mammary tumors
Kiley Graim1,2, Dmitriy Gorenshteyn2,3, David G Robinson2,3
1Flatiron Institute, Simons Foundation, New York, New York 10010, USA.
Abstract:
Understanding the changes in diverse molecular pathways underlying the development of breast tumors is critical for improving diagnosis, treatment, and drug development. Here, we used RNA-profiling of canine mammary tumors (CMTs) coupled with a robust analysis framework to model molecular changes in human breast cancer. Our study leveraged a key advantage of the canine model, the frequent presence of multiple naturally occurring tumors at diagnosis, thus providing samples spanning normal tissue and benign and malignant tumors from each patient. We showed human breast cancer signals, at both expression and mutation level, are evident in CMTs. Profiling multiple tumors per patient enabled by the CMT model allowed us to resolve statistically robust transcription patterns and biological pathways specific to malignant tumors versus those arising in benign tumors or shared with normal tissues. We showed that multiple histological samples per patient is necessary to effectively capture these progression-related signatures, and that carcinoma-specific signatures are predictive of survival for human breast cancer patients. To catalyze and support similar analyses and use of the CMT model by other biomedical researchers, we provide FREYA, a robust data processing pipeline and statistical analyses framework.
Insights
Canine mammary tumors (CMTs) closely mirror human breast cancer molecular pathways. Analyzing multiple tumors per dog revealed progression signatures crucial for understanding cancer development and predicting patient survival.
Area of Science:
- Comparative oncology
- Molecular biology
- Genomics
Background:
- Understanding breast cancer molecular changes is vital for diagnosis and treatment.
- Canine mammary tumors (CMTs) offer a valuable model for human breast cancer research due to naturally occurring tumors.
Purpose of the Study:
- To model human breast cancer molecular changes using canine mammary tumors.
- To identify molecular signatures associated with tumor progression and patient survival.
Main Methods:
- RNA-profiling of canine mammary tumors (CMTs) and normal tissues.
- Utilized a multi-tumor per patient approach to capture tumor heterogeneity.
- Developed and applied a robust data processing and statistical analysis framework (FREYA).
Main Results:
- CMTs exhibit molecular signals (expression and mutation) comparable to human breast cancer.
- Identified distinct transcription patterns and biological pathways specific to malignant versus benign tumors.
- Carcinoma-specific signatures derived from CMTs are predictive of survival in human breast cancer patients.
Conclusions:
- The canine mammary tumor model effectively recapitulates human breast cancer molecular characteristics.
- Analyzing multiple tumors per patient is essential for identifying progression-related molecular signatures.
- FREYA provides a valuable resource for researchers utilizing the CMT model for cancer studies.
