A complete and extensive mapping of healthy breast cells is now available online. It’s a new tool to study how breast cancer develops and the differences in breast tissue among genetic ancestries.
Harikrishna Nakshatri, PhD, senior author of the study told Inside Precision Medicine that while previous studies of normal breast tissue have been done, theirs is unique. “We used breast tissues from clinically breast cancer free women. Other studies used samples from reduction mammoplasty, which we and others have shown to histologically abnormal. Our study included samples from women of diverse genetic ancestry so that data are applicable to all people.”
In a paper published this month in Nature Medicine, the researchers present a comprehensive atlas of breast tissue cells—including details on how the genome is organized in each cell type and the effects of this genome organization on how RNA is made in each cell type to drive their function in various parts of the breast—using healthy breast tissue from women of diverse ancestry.
“Breast cancer shows variability in the outcome based on your genetic ancestry,” said Nakshatri. “While socio-economics are certainly a contributing factor, we believe biology and ancestry also play a role. This study will help us to address that biological, ancestral aspect.”
Nakshatri’s lab sequenced 88,000 cell nuclei from 92 women who donated healthy breast tissue to the Komen Tissue Bank at the IU Simon Comprehensive Cancer Center. The donors included people of African, European, Indigenous American, Hispanic, East Asian, Southeast Asian and Ashkenazi-Jewish-European ancestry.
The cell mapping includes data not only on the genes expressed in various cell types, but also on how the genes are organized and what specific gene expressions are limited to each cell type. Researchers know breast cancer most often originates in specific cell types and where it originates leads to different cancer type and treatment responses. This study could improve understanding of breast cancer development and lead to identifying new treatment targets.
“This research aimed to understand the building blocks of the normal breast—meaning how many different cell types exist in the normal breast and do the building blocks of the cells show genetic ancestry-dependent variability,” Nakshatri said. “Unless we know from which cell types of the breast the cancer originates, we can’t really figure out what exactly is going wrong in breast cancer compared to the normal breast.”
Previously available research resources have used normal tissue from breast cancer surgeries and reduction mammoplasty samples. The Komen Tissue Bank, the world’s only healthy breast tissue bank, offered IU researchers a unique opportunity for this study.
“We are using tissue from women who are clinically free of breast cancer; for that reason, we do believe the data that we created are close to perfect—truly the closest you can get,” Nakshatri said. “The data we generated from this is going to stay in perpetuity because it’s going to be used by many, many groups for future research.”
They also have several types of useful data, he said, including: extensive analyses of lobular and ductal epithelial cells, data from the same donor but whose tissues were collected 10 years apart, a gene expression pattern and a relationship between gene expression and chromatin organization.
Nakshatri is the Marian J. Morrison Professor of Breast Cancer Research at the IU School of Medicine and a researcher of the Vera Bradley Foundation Center for Breast Cancer Research at the IU Simon Comprehensive Cancer Center.
The cell atlas information from the study will be broadly available to breast cancer researchers through databases offered by the National Institutes of Health, Human Cell Atlas, CELLxGENE, and Nature Medicine.
