Study of the Impact of Neoadjuvant Therapy on the Heterogeneity of Triple Negative Breast Cancer Through Single-cell RNA Sequencing (scRNAseq) and Whole-exome Sequencing (WES)

Triple negative breast cancer (TNBC) represents approximately 15-20% of all breast cancers. Its features are lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). TNBC exhibits a biologically aggressive behavior and a high inter- and intra-tumor molecular heterogeneity which has recently been highlighted also in single cell RNAseq (scRNAseq) studies. Patients with TNBC often have less positive outcomes then other breast cancer subtypes, due to the absence of specific therapeutic targets.

Results of single cell RNA sequencing (scRNAseq) in TNBC before and after treatment with chemotherapy (NAC) were recently reported for a small group of patients. Genetic alterations are also investigated by Whole Exome Sequencing (WES).

In addition scRNAseq analysis confirmed the presence of a high percentage of M2 macrophages in TNBC and tumor-adjacent tissue. These macrophages are clinically relevant and able to predict outcome in TNBC.

Based on the above evidence, we hypothesize that molecular characterization of persistent tumor cells remaining after NAC and infiltrating immune cells, for example, M2 macrophages, could strongly contribute to identifying targeted therapeutic approaches for this disease.

We will conduct a pilot study with a combined retrospective and prospective observational design.