Study Identifies Breast Cancer ‘Cells-of-Origin’ in High-Risk Women

Researchers from the Walter and Eliza Hall Institute have achieved a significant milestone in understanding the origins of breast cancer in individuals carrying the BRCA2 mutation. Their findings, published in Nature Cell Biology, shed light on specific cells that may play a crucial role in the development of breast cancer in BRCA2 carriers.

The study compared cancer-free tissue samples from both BRCA2 carriers and non-carriers. The researchers identified a distinct population of cells, known as luminal progenitor cells, that exhibited abnormal division in the majority of tissue samples from women with a faulty BRCA2 gene. These aberrant cells are believed to be the potential "cells-of-origin" that lead to future breast cancers in BRCA2 mutation carriers.

What makes these luminal progenitor cells stand out is their altered protein production, a factor essential for the correct growth and functioning of tissues in our bodies. According to Dr. Rosa Pascual, one of the study's authors, these changes might render the cells more susceptible to certain therapies designed to prevent or delay breast cancer development.

To validate their findings, the research team developed a pre-clinical BRCA2 model and targeted the identified abnormal cells with the cancer drug everolimus, already approved for treating relapsed breast cancer. The pre-treatment with everolimus demonstrated a delay in tumor formation in the laboratory setting, suggesting a potential avenue for breast cancer prevention in BRCA2 mutation carriers.

Lead author Professor Jane Visvader emphasized the importance of pinpointing vulnerabilities in protein production, stating that targeting specific aspects of protein production could represent a novel strategy for preventing breast cancer in women with a faulty BRCA2 gene.

However, it's essential to note that more work is needed before these findings can be applied in clinical settings. Professor Geoff Lindeman, a cancer clinician and study author, highlighted that while everolimus showed promise in delaying tumor development, its side-effects could limit its use as a preventative treatment. The research team aims to delve deeper into understanding the specific dysregulations in protein processing and use this knowledge to develop more selective and tolerable preventative treatments.

Despite the need for further research, these findings mark a crucial first step toward the goal of preventative treatments for breast cancer in BRCA2 mutation carriers. Similar breakthroughs in the past have led to international breast cancer prevention studies, and researchers hope that this discovery will inform future treatments and prevention strategies for women with a faulty BRCA2 gene.