FAT-metBC: Facing increased Adiposity in Treating metastatic Breast Cancer

In industrialized countries, approximately 1 out 8 women will develop breast cancer (BC) in her lifetime and 1 out of 2 is overweight or obese. While heavier BC patients are at higher risk of recurrence and death, BC is so far still treated independently of the patient’s adiposity because of the limited knowledge accumulated so far, specifically at the metastatic level. Autopsy programs represent a unique opportunity for research since they allow the collection of multiple samples from the metastasized disease. Here, we aim at unraveling how increased adiposity affects disease progression by applying novel pathology and omics technologies to samples collected in the context of autopsy programs from lean and overweight/obese patients who died from their disease. Specifically: 1) using digital pathology, we will describe the fat cells at different location and describe the inflammation potentially present in the adipose tissue; 2) using sequencing, we will reconstruct the genomic evolution of the disease; 3) using lipidomics, we will identify aberrant lipid profiles in the blood and in the metastases; and, 4) using RNA sequencing, we will monitor the changes in gene expression in the metastases according to patient adiposity. Finally, for a few patients, we will apply the latest single-cell RNA sequencing technology to identify important changes in the normal versus tumoral tissue according to adiposity. Importantly, the investigators have already successfully worked together in reconstructing the phylogenetic evolution of BC on patients from the Semmelweis autopsy program (Brown et al. Nat Comms 2017). We anticipate that results generated in this project will significantly contribute to a better understanding of the impact of obesity on BC progression and will also have a high translational potential, as they will likely open new opportunities toward personalized treatment strategies in heavier BC patients.

Keywords:Breast Cancer, Obesity, Metabolism, Metastasis, Prognosis

Disciplines:Cancer therapy