Research pinpoints breast cancer origin cells in at-risk females

Abnormal luminal cells and mTORC1 may prevent breast cancer in BRCA2 mutation carriers.

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Women with a faulty BRCA2 gene face a high 70% risk of developing breast cancer. These cancers are often aggressive and occur at a young age. Early screening and preventive measures like mastectomy are recommended. A significant breakthrough in Nature Cell Biology reveals that researchers found the likely starting cells of cancer in BRCA2 carriers. 

They identified cells that divide rapidly by comparing tissue samples from pages and non-carriers. This discovery holds promise for understanding and potentially preventing breast cancer in high-risk individuals.

Study joint first author Dr Rachel Joyce said, “This perturbed cell population was found in most 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.

Women with a faulty BRCA2 gene face a high 70% risk of developing breast cancer. These cancers are often aggressive and occur at a young age. Early screening and preventive measures like mastectomy are recommended. 

A significant breakthrough in Nature Cell Biology reveals that researchers found the likely starting cells of cancer in BRCA2 carriers. They identified cells that divide rapidly by comparing tissue samples from pages and non-carriers. This discovery holds promise for understanding and potentially preventing breast cancer in high-risk individuals.

Prof. Visvader from WEHI reveals that targeting a vulnerability in protein production delays tumor formation in a pre-clinical model. This discovery suggests a potential new strategy for preventing breast cancer in women with a faulty BRCA2 gene.

The findings are a crucial first step toward preventing breast cancer in those with BRCA2 mutations. Professor Geoff Lindeman, the study author, acknowledges the excitement but emphasizes the need for more research before applying it in clinics. The drug everolimus, while delaying tumor development in the lab, has potential side effects that might limit its use as a preventative treatment, according to Prof Lindeman, a medical oncologist at the Royal Melbourne Hospital and Peter MacCallum Cancer Centre.

Prof Lindeman said, “Our team aims to explore specific parts of protein processing that are disrupted and use this knowledge to create more targeted and tolerable preventive treatments. Though there’s more work ahead, we’ve taken a significant step. A few years ago, we identified potential starting cells for breast cancer in those with a faulty BRCA1 gene, leading to an international prevention study. We believe our new findings will guide future treatments and prevention for women with a faulty BRCA2 gene.”

This study marks a significant advancement in unraveling the mysteries of breast cancer initiation in high-risk women. The identification of ‘cells-of-origin’ opens avenues for targeted preventive measures, offering hope for a future where personalized interventions mitigate the risk of breast cancer in individuals with a genetic predisposition, particularly those with a faulty BRCA2 gene.

Journal reference:

  1. Joyce, R., Pascual, R., Heitink, L. et al. Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers. Nature Cell Biology. DOI: 10.1038/s41556-023-01315-5.

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