Normal Breast Cells Show Mutations Linked to Cancer Risk

Scientists at MD Anderson Cancer Center found that some normal-looking breast cells in healthy women have genetic changes linked to breast cancer. This challenges the idea that cancer starts only when these mutations appear. Instead, it suggests that some of these changes exist long before cancer develops, raising new questions about how and when cancer actually begins.

In a study of 49 healthy women, at least 3% of their normal breast cells had extra or missing chromosomes, a condition called aneuploidy. These changes became more common with age. Researchers used single-cell sequencing and spatial mapping to study individual cells and found that many of these genetic changes matched those seen in invasive breast cancer. The most frequent changes included gains in chromosome 1q and losses in chromosomes 10q, 16q, and 22, regions known to contain genes associated with breast cancer.

The study focused on epithelial cells, the type of cells that line and cover surfaces inside the body. These cells are believed to be the ones that eventually turn cancerous. Researchers found that these abnormal cells were present in both major types of breast cell lineages. One group of cells had changes similar to estrogen receptor-positive breast cancers, while the other resembled estrogen receptor-negative breast cancers. This suggests that different types of breast cancer may develop from distinct pathways in the body.

Since these genetic changes are found in healthy women, they may complicate early cancer detection methods. Molecular tests and biopsies might mistake these cells for cancer, leading to false positives. This raises important questions about how doctors should interpret genetic findings in breast tissue and whether current methods for identifying cancer need to be refined.

The research also suggests that aneuploidy may be a normal part of aging, not just a sign of cancer. Similar abnormal cells exist in different parts of the body, meaning this discovery could apply to other types of cancer as well. Scientists emphasize that this does not mean every woman with these cells will develop breast cancer, but it highlights the need for larger, long-term studies to understand which risk factors might cause these cells to turn cancerous.

This study builds on previous research, including the Human Breast Cell Atlas, which mapped over 714,000 breast cells to better understand how normal breast tissue functions. The findings could change how scientists approach early cancer detection and prevention by focusing on identifying which genetic changes are truly dangerous and which are simply part of normal cell variation.