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Project

Dissection of molecular determinants of metastasis and detailed characterization of the age-related immunological profile in (older) patients with hormone-sensitive breast cancer

This PhD project’s main objective is to better understand and characterize the tumor biology and immunology of HR+/HER2- breast cancer in (older) patients. First, we want to improve our understanding of the metastatic process in HR+/HER2- breast cancer (i) by evaluating the potential correlations of various circulating plasma/serum biomarkers with development of secondary metastases, and (ii) by comparing transcriptomic profiles of primary metastasized and non-metastasized tumors at breast cancer diagnosis. Secondly, we will further explore the tumor microenvironment of HR+/HER2- breast tumors via a new multiplex immunohistochemistry technique called “MILAN” (multiple iterative labeling by antibody neodeposition), to gain deeper insight into tumor immune response in relation with age. Thirdly, we will evaluate the toxicity of CDK4/6 inhibitors in (frail) older patients with metastasized HR+/HER2- breast cancer by evaluating the impact of the combination treatment (CDK4/6 inhibitors plus endocrine therapy) on the immune system in relation to the patients’ clinical frailty profile.

Concrete project aims:

- To identify baseline circulating metastasis-related factors that hold potential as prognostic blood biomarkers predicting subsequent distant recurrence of HR+/HER2- breast cancer.

- To study the differences in tumor gene expression of de novo/primary metastatic breast cancer versus non-primary metastatic HR+/HER2- breast cancer.

- To characterize the ‘tumor immune landscape’ of HR+/HER2- breast cancer, and evaluate the impact of aging on it.

- To evaluate the impact of endocrine therapy combined with CDK4/6 inhibition on the host immune system of older patients with metastatic HR+/HER2- breast cancer.

Date:1 Sep 2019 →  11 Dec 2023
Keywords:Cancer, Tumour biology, Biomarkers ageing, Biomarkers cancer, Geriatric oncology, Breast cancer, Clinical trial, Tumor microenvironment, Immunology
Disciplines:Cancer diagnosis, Cancer biology, Geriatrics
Project type:PhD project