Related Experiment Video
Updated: Mar 17, 2026
A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer
Published on: December 26, 2016
The genomic landscape of breast cancer and its interaction with host immunity
Stephen Luen1, Balaji Virassamy1, Peter Savas1
1Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
Abstract:
Molecular profiling of thousands of primary breast cancers has uncovered remarkable genomic diversity between breast cancer subtypes, and even within subtypes. Only a few driver genes are recurrently altered at high frequency highlighting great challenges for precision medicine. Considerable evidence also confirms the role of host immunosurveillance in influencing response to therapy and prognosis in HER2+ and triple negative breast cancer. The role of immunosurveillance in ER + disease remains unclear. Advances in both these fields have lead to intensified interest in the interaction between genomic landscapes and host anti-tumour immune responses in breast cancer. In this review, we discuss the potential genomic determinants of host anti-tumour immunity - mutational load, driver alterations, mutational processes and neoantigens - and their relationship with immunity in breast cancer. Significant differences exist in both the genomic and immune characteristics amongst breast cancer subtypes. While ER + disease appears to be less immunogenic than HER2+ and triple negative breast cancer, it displays the greatest degree of heterogeneity. Mutational and neoantigen load appears to incompletely explains immune responses in breast cancer. Driver alterations do not appear to increase immunogenicity. Instead, they could contribute to immune-evasion or an immunosuppressive microenvironment, and therefore represent potential therapeutic targets. Finally, we also discuss the tailoring of immunotherapeutic strategies by genomic alterations, with possible multimodal combination approaches to maximise clinical benefits.
Insights
Genomic diversity in breast cancer impacts immune responses. While driver mutations may not boost immunity, they can promote immune evasion, offering new therapeutic targets for precision medicine.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Breast cancer exhibits significant genomic heterogeneity across subtypes.
- Host immunosurveillance influences therapy response and prognosis in HER2+ and triple-negative breast cancer, but its role in ER+ disease is unclear.
- Interactions between genomic landscapes and anti-tumor immune responses are crucial in breast cancer.
Purpose of the Study:
- To review potential genomic determinants of anti-tumor immunity in breast cancer.
- To explore the relationship between genomic characteristics and immune responses across breast cancer subtypes.
- To discuss tailoring immunotherapeutic strategies based on genomic alterations.
Main Methods:
- Review of existing literature on molecular profiling and host immunosurveillance in breast cancer.
- Analysis of genomic determinants including mutational load, driver alterations, mutational processes, and neoantigens.
- Comparison of genomic and immune characteristics across different breast cancer subtypes (ER+, HER2+, triple-negative).
Main Results:
- Significant genomic and immune differences exist among breast cancer subtypes.
- ER+ breast cancer is less immunogenic but more genomically heterogeneous than HER2+ and triple-negative subtypes.
- Mutational and neoantigen load partially explain immune responses; driver alterations may promote immune evasion rather than increase immunogenicity.
Conclusions:
- Genomic alterations can influence immune evasion and the tumor microenvironment, presenting potential therapeutic targets.
- Driver alterations may not enhance immunogenicity but could be targeted for immune-modulating therapies.
- Genomic profiling can guide personalized immunotherapeutic strategies, including multimodal combinations for improved clinical outcomes.
Related Concept Videos
02:17The Tumor Microenvironment
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...