Identification of tumor characteristics influencing long-term risk of distant metastatic disease and endocrine treatment benefit in ER+ breast cancer

Most breast cancer patients are diagnosed with hormone-dependent (estrogen receptor-positive, ER+) breast cancer and endocrine treatment is standard of care.

A unique feature of ER+ disease is that the risk to develop distant metastasis remains stable beyond 5-10-years after diagnosis, and half or more of all metastases will be diagnosed after this initial follow-up.

The tumor biological factors underlying long-term risk are poorly understood, and it will remain a considerable clinical challenge in the foreseeable future.

We will investigate the influence of standard clinical markers, their intra-tumor heterogeneity, and the heterogeneous ER+ tumor microenvironment, to identify tumor characteristics influencing long-term risk and benefit from endocrine treatment.

Novel deep-learning methods will be used and in depth spatial analysis will enable understanding of tumor biology down to single-cell level.

We will use unique and large clinical trials with patients randomized to endocrine treatment versus not with complete long-term follow-up.

The distinction of long-term risk is essential, since accurate risk prediction allows for individualized treatment, decreases anxiety, and supports aggressive treatment for patients at high risk of fatal disease.

Our study has the potential to answer vital questions about the influence of the tumor microenvironment and intra-tumor heterogeneity for long-term risk in ER+ breast cancer, helped by the interdisciplinary expertise in our team.