A recent study reveals that some breast cells, which seem normal in otherwise healthy women, may harbor chromosome abnormalities similar to those found in invasive breast cancer. This challenges the traditional understanding of the genetic origins of breast cancer and might impact early detection strategies. The research shows that at least 3% of healthy breast tissue cells from 49 women exhibit chromosomal variations, known as aneuploidy, with these variations increasing as the women age.
A recent study from researchers at The University of Texas MD Anderson Cancer Center indicates that in healthy women, certain breast cells that seem normal may actually have chromosome abnormalities linked to invasive breast cancer. These findings challenge the traditional beliefs about the genetic basis of breast cancer, which could affect early detection techniques.
The study, published today in Nature, found that at least 3% of normal cells in breast tissue from 49 healthy women show gains or losses of chromosomes, a condition referred to as aneuploidy, which tends to increase with age. This raises questions about our perception of “normal” tissues, as noted by the principal investigator Nicholas Navin, Ph.D., chair of Systems Biology.
As researchers strive to create earlier detection methods utilizing molecular diagnostics along with ductal carcinoma in situ (DCIS) and biopsies, these results present challenges and underscore the risk of false positives, where normal cells might be mistakenly identified as invasive breast cancer.
“A cancer researcher or oncologist interpreting the genomic data of these normal breast tissue cells might categorize them as invasive breast cancer,” Navin stated. “We’ve always been taught that normal cells contain 23 pairs of chromosomes, but our study highlights inaccuracies in this belief since every healthy woman we evaluated had some form of chromosome irregularity, raising critical questions regarding when cancer truly begins.”
This study builds on Navin’s earlier research involving the Human Breast Cell Atlas, which cataloged over 714,000 cells to create a detailed genetic map of normal breast tissue at the cellular level.
For the current investigation, researchers analyzed samples from 49 healthy women who had no known diseases and were undergoing breast reduction surgery. They looked at chromosomal changes in normal breast tissues alongside data from clinical breast cancer cases.
Through single-cell sequencing and spatial mapping, the researchers focused on breast epithelial cells. Navin highlights that these epithelial cells, which line or cover various body surfaces, are recognized as the potential origin of breast cancer.
The study found that on average, 3.19% of the epithelial cells in the examined normal breast tissues were aneuploid, with over 82.67% showing chromosomal changes commonly observed in invasive breast cancers. Notably, there was a significant correlation between a woman’s age and the presence of aneuploid cells and chromosomal changes, indicating that older women experienced a higher accumulation of these cellular alterations.
The most prevalent changes identified included extra copies of chromosome 1q and losses of chromosomes 10q, 16q, and 22, all commonly seen in invasive breast cancers. Previous research has pinpointed specific genes within these regions that are also linked to breast cancer, according to Navin.
The findings further demonstrate that these aneuploid cells encompass both recognized cell lineages of the mammary gland, which possess unique gene signatures that may indicate either positive or negative estrogen receptor (ER) characteristics. One lineage exhibited copy number changes typical of ER-positive breast cancers, while the other appeared to be associated with events indicative of ER-negative breast cancers, suggesting different potential origins.
Navin emphasizes that this report focuses on rare aneuploid cells found in the normal population, necessitating further longitudinal research to determine whether any risk factors might convert these cells into cancer. Additionally, since epithelial cells are present in various bodily systems, there’s potential for these insights to apply to other organs as well.
“This indicates some imperfections in our bodies, leading to the formation of these cell types throughout our lives,” Navin remarked. “The implications of this are significant not only for breast cancer research but potentially across various cancer types. This doesn’t imply that every individual has precancerous cells, but it’s vital to explore larger studies to better understand the consequences for cancer development.”
This study received support from the National Cancer Institute (RO1CA240526, RO1CA236864, 1R01CA234496, F30CA243419), the Cancer Prevention and Research Institute of Texas (CPRIT) Single Cell Genomics Center (RP180684), the American Cancer Society, and the Rosalie B. Hite Fund for Cancer Research Fellowship.
