Abstract P3-05-16: A mathematical model for predicting immune response in a trastuzumab treated HER2+ breast cancer animal model: Preliminary efforts

2018 ◽  
Author(s):  
AM Jarrett ◽  
TE Yankeelov ◽  
LI Ehrlich ◽  
W Godfrey ◽  
AG Sorace
Keyword(s):  
Breast Cancer ◽  
Mathematical Model ◽  
Immune Response ◽  
Animal Model ◽  
Her2 Breast Cancer

scholarly journals Mathematical modelling of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer

2018 ◽  
Vol 36 (3) ◽  
pp. 381-410 ◽  
Author(s):  
Angela M Jarrett ◽  
Meghan J Bloom ◽  
Wesley Godfrey ◽  
Anum K Syed ◽  
David A Ekrut ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Experimental Data ◽  
Mathematical Model ◽  
Immune Response ◽  
Immune System ◽  
Murine Model ◽  
Tumour Growth ◽  
Experimental Approach ◽  
Her2 Breast Cancer ◽  
The Mathematical Model

Abstract The goal of this study is to develop an integrated, mathematical–experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer. Sensitivity analysis shows that model components are sensitive for 12 of 13 parameters, but accounting for uncertainty in the parameter values, model simulations still agree with the experimental data. Given theinitial conditions, the mathematical model predicts an increase in the immune infiltrates over time in the treated animals. Immunofluorescent staining results are presented that validate this prediction by showing an increased co-staining of CD11c and F4/80 (proteins expressed by dendritic cells and/or macrophages) in the total tissue for the treated tumours compared to the controls ($p < 0.03$). We posit that the proposed mathematical–experimental approach can be used to elucidate driving interactions between the trastuzumab-induced responses in the tumour and the immune system that drive the stabilization of vasculature while simultaneously decreasing tumour growth—conclusions revealed by the mathematical model that were not deducible from the experimental data alone.

scholarly journals Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2− Breast Cancer

2019 ◽  
Vol 26 (3) ◽  
pp. 566-580 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Michael F. Press ◽  
David Chan ◽  
María Fernandez-Abad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Immune Response ◽  
Phase Ii ◽  
Her2 Breast Cancer ◽  
Cell Cycle Inhibition

scholarly journals Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 245
Author(s):  
Reza Mehdizadeh ◽  
Seyed Peyman Shariatpanahi ◽  
Bahram Goliaei ◽  
Sanam Peyvandi ◽  
Curzio Rüegg
Keyword(s):  
Breast Cancer ◽  
Mathematical Model ◽  
Immune Response ◽  
Growth Rate ◽  
T Lymphocyte ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Type I ◽  
Type I Ifn ◽  
Cancer Dormancy

Triple-negative breast cancer (TNBC) is a molecular subtype of breast malignancy with a poor clinical prognosis. There is growing evidence that some chemotherapeutic agents induce an adaptive anti-tumor immune response. This reaction has been proposed to maintain the equilibrium phase of the immunoediting process and to control tumor growth by immunological cancer dormancy. We recently reported a model of immunological breast cancer dormancy based on the murine 4T1 TNBC model. Treatment of 4T1 cells in vitro with high-dose chemotherapy activated the type I interferon (type I IFN) signaling pathway, causing a switch from immunosuppressive to cytotoxic T lymphocyte-dependent immune response in vivo, resulting in sustained dormancy. Here, we developed a deterministic mathematical model based on the assumption that two cell subpopulations exist within the treated tumor: one population with high type I IFN signaling and immunogenicity and lower growth rate; the other population with low type I IFN signaling and immunogenicity and higher growth rate. The model reproduced cancer dormancy, elimination, and immune-escape in agreement with our previously reported experimental data. It predicted that the injection of dormant tumor cells with active type I IFN signaling results in complete growth control of the aggressive parental cancer cells injected at a later time point, but also of an already established aggressive tumor. Taken together, our results indicate that a dormant cell population can suppress the growth of an aggressive counterpart by eliciting a cytotoxic T lymphocyte-dependent immune response.

Abstract P6-10-17: Breast MRI as a radiomic biomarker of immune response in HER2+ breast cancer

2020 ◽  
Author(s):  
Laura Carpin Kennedy ◽  
Grace Durenberger ◽  
Sasha E. Stanton ◽  
Shaveta Vinayak ◽  
Suzanne Dintzis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Breast Mri ◽  
Her2 Breast Cancer

Breast MRI as a radiomic biomarker of immune enrichment in HER2+ breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14281-e14281
Author(s):  
Laura Kennedy ◽  
Grace Durenberger ◽  
Sasha E. Stanton ◽  
Shaveta Vinayak ◽  
Suzanne Dintzis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
Functional Mri ◽  
Strong Correlation ◽  
Statistical Significance ◽  
Breast Mri ◽  
Invasive Technique ◽  
Her2 Breast Cancer ◽  
Potential Biomarker

e14281 Background: Trastuzumab is an important drug in the treatment (tx) of HER2+ breast cancer, but not all tumors are responsive. Immune-enriched tumors have a better response to tx, and a biomarker to identify these tumors would be valuable. Multiparametric functional MRI is a non-invasive technique that can assess the entire tumor without the sampling error of biopsy. In this pilot study, we evaluate breast MRI as a potential biomarker for tumor immune response to trastuzumab. Methods: Women with de novo cT1-2N0 HER2+ breast cancer were enrolled and received paired multiparametric breast MRI examinations (including DWI and DCE sequences) prior to and ~2 weeks after a single dose of trastuzumab, followed by surgery or biopsy (if additional neoadjuvant tx planned). Tumor peak signal enhancement ratio (SER) and mean apparent diffusion coefficient (ADC), reflecting tissue perfusion and tissue cellularity, were determined from the images. Pre- and post-tx tissue were immunologically profiled with TIL counts and an immune-focused RNA gene expression panel. SER and ADC were correlated with TIL and RNA gene expression using Spearman’s rho. Results: To date, 8 women have enrolled and 6 had pre- and post-tx tissue available. The primary endpoint was correlation between SER and ADC measurements with tumor TILs. Secondary endpoints included correlating SER with angiogenesis and inflammation markers and correlating changes in SER and ADC with apoptosis/cell death markers. About half of the patients had TIL-enriched (TIL≥ 50%) tumors at baseline, and after trastuzumab the majority of tumors remained enriched or had an increase in TILs. Results suggest that pre-tx ADC had a negative correlation with TILs by histology and gene expression, although correlations did not reach statistical significance in this small cohort. Results also suggest a strong correlation between pre-tx SER and VEGF-A (r = 0.83) with a trend towards significance (P = 0.10). A decrease in SER post-tx had a strong correlation with an increase in caspase 3 expression (r = -0.85, p = 0.05), which suggested tx effect. Conclusions: Functional MRI may provide a novel biomarker of breast tumor immune response to trastuzumab. Results from additional patients will be available at the meeting.

scholarly journals Assessing the Effects of Estrogen on the Dynamics of Breast Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Chipo Mufudza ◽  
Walter Sorofa ◽  
Edward T. Chiyaka
Keyword(s):  
Breast Cancer ◽  
Mathematical Model ◽  
Immune Response ◽  
Risk Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Population Model ◽  
Host Cells ◽  
Common Cancer ◽  
General Dynamics

Worldwide, breast cancer has become the second most common cancer in women. The disease has currently been named the most deadly cancer in women but little is known on what causes the disease. We present the effects of estrogen as a risk factor on the dynamics of breast cancer. We develop a deterministic mathematical model showing general dynamics of breast cancer with immune response. This is a four-population model that includes tumor cells, host cells, immune cells, and estrogen. The effects of estrogen are then incorporated in the model. The results show that the presence of extra estrogen increases the risk of developing breast cancer.

scholarly journals Pathogenesis of anti-Yo positive paraneoplastic cerebellar degeneration

SURG Journal ◽  
1969 ◽  
Vol 1 (1) ◽  
pp. 42-50
Author(s):  
Laura Pepler ◽  
Carol Armstrong
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Animal Model ◽  
Cytotoxic T Lymphocytes ◽  
Symptomatic Treatment ◽  
Cerebellar Degeneration ◽  
Paraneoplastic Cerebellar Degeneration ◽  
Immune Mediated ◽  
Suitable Animal Model ◽  
Pathogenic Process

Paraneoplastic cerebellar degeneration (PCD) is a neurological disorder affecting the cerebellum and is believed to be immune-mediated. Anti-Yo PCD is associated with gynaecological and breast cancer tumours and the presence of these tumours is believed to invoke an immune response. The immune response includes both anti-Yo antibodies and cytotoxic T-lymphocytes that are specific for the Cdr2 antigen expressed in Purkinje cells of the cerebellum. Although both have been implicated in the pathogenic manifestation of PCD neither have been shown to be directly involved. The detection of the anti-Yo antibody greatly aids in the diagnosis of PCD and helps in uncovering the underlying neoplasm before it becomes symptomatic. Treatment of PCD has been targeted at suppressing the immune response but has been unsuccessful so far. The lack of a suitable animal model makes it difficult to study the pathogenic process directly leaving many questions unanswered about PCD pathogenesis.

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