The prognostic and therapeutic impact of intra-tumor heterogeneity in estrogen receptor-positive breast cancer

Approximately 50% of patients with estrogen receptor (ER)-positive breast cancer do not benefit from anti-hormonal (endocrine) treatment, and around one out of four will die from the disease, some decades after primary diagnosis.

It is currently not possible to accurately predict the long-term risk for fatal disease, and the biological factors influencing this risk are not well understood. Our goal is to improve the prediction of patients’ risk for fatal breast cancer.

Tumors with marked intra-tumor heterogeneity may shed tumor cells with different characteristics some of which may enable tumor cell invasion and survival at a distant site.

We will determine the influence of intra-tumor heterogeneity on the risk of fatal breast cancer and on the benefit of endocrine treatment.

Intra-tumor heterogeneity of the clinically used tumor characteristics as well as other tumor characteristics will be evaluated.

We will use unique and large clinical trials performed in Stockholm with patients randomized to endocrine therapy versus not and a follow-up of at least 20-years.

To establish heterogeneity we will use pathologist scored immunohistochemistry, an automated image analysis tool that we are developing, and inter-cell heterogeneity of genes expressed within the same tumor.

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