Targeting tired immune cells to prevent breast cancer

Mapping cellular shifts in the adult human breast.

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Researchers at the University of Cambridge created an extensive collection of human breast cells. Cell alterations have been discovered early in healthy individuals with BRCA1 and BRCA2 gene mutations.

This discovery is exciting because it could mean a new way to prevent breast cancer without surgery for people with these gene mutations, according to Walid Khaled.

All individuals possess the BRCA1 and BRCA2 genes; however, heritable mutations in these genes raise the risk of developing breast and ovarian cancer. The findings demonstrated that the immune cells in the breast tissue of healthy women with mutations in the BRCA1 or BRCA2 gene are dysfunctional. This implies they cannot eliminate damaged breast cells, which may eventually.

This is the first time that ‘exhausted’ immune cells have been widely discovered in healthy breast tissues by researchers. These cells are typically limited to advanced malignancy. 

These results imply that, in individuals with BRCA1 and BRCA2 gene mutations, immunotherapy medications could be used early to prevent breast cancer.

Professor Walid Khaled from the University of Cambridge said, “Our results show that in people with BRCA mutations, the immune system can’t kill damaged breast cells. Those cells seem to be stopping the immune system from working.”

Khaled stated, “We’re excited about this discovery as it hints at a potential new approach to prevent breast cancer in individuals with BRCA gene mutations without resorting to surgery.” By emphasizing the significance of utilizing drugs that target immune cell dysfunction, a strategy not previously considered for preventive measures. 

Published in Nature Genetics, the study illuminates the challenges of risk-reducing surgeries, particularly for young women, underscoring their profound impact on body image and relationships. 

Khaled emphasized the importance of understanding breast cancer’s early stages to intervene effectively, highlighting the difficulty in treating late-stage tumors due to their unpredictability. The research, which examined breast tissue from 55 women of varying ages, identified over 800,000 cells, providing insights into breast cell types and potential avenues for intervention.

The Human Breast Cell Atlas, a valuable resource for researchers, now offers insights into various risk factors for breast cancer, such as BMI, menopausal status, contraceptive use, and alcohol consumption. According to Austin Reed, a PhD student at the University of Cambridge, the atlas reveals that different breast cell types change with pregnancy and age, impacting breast cancer risk. 

Gathering more global data can enhance understanding of breast cancer development and risk factors, aiming to improve treatments. Breast cancer is complex, with various genetic variations and interactions with other risk factors. For instance, while age increases breast cancer risk, early pregnancy reduces it. Yet, carriers of BRCA1 and BRCA2 genes face heightened age-associated risk.

The study aimed to understand how different factors affect breast cancer risk by examining various cell types in the human breast under different conditions. Using a single-cell RNA-sequencing method, researchers identified different breast cell types and their functions based on which genes were active in each cell. 

Dr. Sara Pensa, a Senior Research Associate at the University of Cambridge, emphasized the importance of prevention in addressing global breast cancer disparities and improving outcomes, especially in low-income countries.

Journal reference:

  1. Reed, A.D., Pensa, S., Steif, A., et al. A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast. Nature Genetics. DOI: 10.1038/s41588-024-01688-9.
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