Australian scientists have pinpointed likely ‘cells-of-origin’, the source cells that can grow into breast cancer, in women carrying a faulty BRCA2 gene who are at high risk of developing the disease.
The WEHI-led study also showed these cells have potential to be targeted with an existing cancer drug to delay tumour growth, in findings that may lead to future preventive treatments for the disease.
Women who inherit and carry a faulty BRCA2 gene have a substantially increased risk of developing breast cancer — approximately 70% of carriers will develop the disease over their lifetime.
These cancers often occur at a young age and can be clinically aggressive. Early screening is encouraged and some women undertake preventive breast surgery (mastectomy) to reduce their breast cancer risk.
In a milestone finding published in Nature Cell Biology, researchers have discovered the likely ‘cells-of-origin’ of cancer in BRCA2 carriers. By comparing cancer-free tissue samples from both carriers and non-carriers, they identified an aberrant population of cells that divide more quickly.
Study joint first author Dr Rachel Joyce said this perturbed cell population was found in the majority of tissue samples from women with a faulty BRCA2 gene.
“Given they were found in most of the BRCA2 tissue samples from healthy females, we believe these may be the cells-of-origin that lead to future breast cancers in women that carry the BRCA2 mutation,” Dr Joyce said.
Lead author Professor Jane Visvader said the team developed a pre-clinical BRCA2 model that showed similar alterations in the ductal cells, and targeted them with the existing cancer drug everolimus, which is approved to treat patients with relapsed breast cancer.
“Through pinpointing this vulnerability in protein production, we were able to show that pre-treatment with this drug delayed the formation of tumours in the pre-clinical model,” said Prof Visvader, joint head of the ACRF Cancer Biology and Stem Cells Division and the Breast Cancer Laboratory at WEHI.
“This raises the possibility that targeting specific aspects of protein production in this way could represent a new breast cancer prevention strategy for women with a faulty BRCA2 gene.”
