How we classify cancer and spot it in its earliest stages could need an urgent rethink: researchers have found that even some healthy women carry cells with the key hallmarks of breast cancer.
These cells are known as aneuploid cells, and have an abnormal number of chromosomes. They're common in invasive breast cancer, and it's thought the chromosome imbalance enables cancer to spread and evade the body's immune defenses.
Now it appears aneuploid cells might also be present even when there's no cancer in sight. The researchers, from the University of Texas and the Baylor College of Medicine in Texas, found them in breast tissue samples from 49 healthy women.
"We've always been taught that normal cells have 23 pairs of chromosomes, but that appears to be inaccurate because every healthy woman that we analyzed in our study had irregularities, bringing up the very provocative question about when cancer actually occurs," says biologist Nicholas Navin, from the MD Anderson Cancer Center at the University of Texas.
"A cancer researcher or oncologist seeing the genomic picture of these normal breast tissue cells would classify them as invasive breast cancer."
Using techniques including single-cell sequencing, the team identified the signs of aneuploidy, which were present in around three percent of the total breast epithelial cells analyzed for each woman. Epithelial cells line the inside and outside of the body, and are thought to be where cancer starts.
Most of the aneuploid cells showed copy number alterations, where DNA segments are duplicated or deleted. It's these modifications in particular that are thought to influence cancer progression.
The older the women were, the more often these cellular changes appeared. The most common changes – extra copies of the 1q chromosome and missing 10q, 16q, and 22 chromosomes – are also seen in breast cancer.
Another finding was that the aneuploid cells were mainly found in two breast cell lineages involved in secreting milk: Luminal Hormone Receptor-Positive (LumHR) and Luminal Secretory (LumSec). This suggests different types of breast cancer could develop from different lineages.
What this all means isn't yet clear – but it raises a lot of questions about what normal, healthy tissue actually looks like, how potential false positives might be avoided, and what risk factors might determine whether or not aneuploid cells become cancerous.
"This has pretty big implications not just for the field of breast cancer, but potentially for multiple cancer types," says Navin.
"This doesn't necessarily mean that everyone is walking around with precancer, but we need to think about ways to set up larger studies to understand the implications for developing cancer."
The researchers think the approach they've used here could well reveal aneuploid cells in other parts of the body – and contribute to our understanding of how other types of cancer get started as well.
"Future work in this area will undoubtedly lead to new insights into cancer initiation and begin to address the fundamental question of when a cancer is really a cancer," write the researchers in their published paper.
The research has been published in Nature.