New Findings in Breast Cell Chromosomes May Challenge Early Disease Detection, Benefit Other Organ Disease Detection

In healthy women, some breast cells that otherwise appear normal may contain chromosome abnormalities typically associated with invasive breast cancer, according to new research from the University of Texas MD Anderson Cancer Center and published in Nature. These findings challenge the conventional reasoning behind the genetic origins of breast cancer, which could have an important influence on early cancer detection methods.

The study discovered that in at least 3% of the 49 healthy women included in the study contained a gain or loss of chromosomes, a condition called aneuploidy, which expands and accumulates with age. As researchers expand early detection methods using molecular diagnostics, along with ductal carcinoma in situ and biopsies, these findings highlight the potential risk of identifying false positives in cells that can mistakenly be confused with invasive breast cancer.

Principal investigator Nicholas Navin, PhD, chair of Systems Biology at the University of Texas MD Anderson Cancer Center, previously launched the  Human Breast Cell Atlas, which profiled over 714,000 cells to generate a comprehensive genetic map of normal breast tissue at the cellular level, building on Navin’s previous research.

Using single-cell sequencing and spatial mapping, researchers examined samples from 49 healthy women without known disease who were undergoing breast reduction surgery. They investigated chromosomal copy number changes in normal breast tissues compared with clinical breast cancer data. They specifically investigated breast epithelial cells, which line and cover the inside and outside of the body and are believed to give rise to cancer.

A median of 3.19% of the epithelial cells in the normal breast tissue samples were aneuploid and more than 82.67% had expanded copy number changes commonly found in invasive breast cancers. Of interest, older women accumulated more of these cellular changes, thus implying a correlation with age.

The most frequent changes detected were additional copies of chromosome 1q and losses of chromosomes 10q, 16q, and 22. These data reveal that the aneuploid cells represent both known cell lineages of the mammary gland, which have distinct gene signatures that can either be positive or negative for estrogen receptors. One lineage had copy number changes similar to estrogen receptor-positive disease, whereas the other appeared to have events consistent with estrogen receptor-negative disease, highlighting their potentially different origins.

Dr. Navin noted that further longitudinal studies are warranted to identify which, if any, potential risk factors may lead to these altered cells becoming cancerous. The findings on epithelial cells can potentially be applied to other organs as well, due to their presence in many parts of the body.