Location matters: spatial-dependent effects of myofibroblasts determine survival in breast cancer

In our previous study (PMID: 37863888), we performed multi-regional bulk transcriptomics profiling of 8 ER+/PR+/HER2- breast tumors and matched peri-tumoral tissues. We identified an adipose-enriched peri-tumoral subtype which was significantly associated with poorer overall survival in breast cancer patients, in contrast to a myofibroblast-enriched subtype.

Here, we performed single-nucleus RNA-sequencing of 2 ER+/PR+/HER2- invasive breast carcinomas and their matched peri-tumoral tissues (1-7 cm from tumor margins), as well as 1 reduction mammoplasty (RM) sample. We identified tumor-induced changes in the peri-tumoral adipocytes compared to RM adipocytes, as well as a high abundance of myCAFs in the larger tumor, whereas a distinct myofibroblast-like subpopulation was found in the peri-tumoral tissues of the smaller tumor.