MD Anderson researchers lay bare all the secrets of breast cells

Nipple discharge, fat necrosis, intraductal papillomas, fibroadenomas, cysts, mastitis, tumors…. There are many diseases, benign and malignant, that can affect the breasts at any age in a woman's life.. In order to better diagnose and treat these conditions, it is convenient to study and know breast biology well.. To this end, the largest and most complete map of breast tissue in the world has been created, a monumental project that has lasted seven years and that Nature publishes this Thursday.

Pulling joke, it is not a simple world map of 'tits'. This is a work that has used methods of spatial genomics and single-cell sequencing to describe more than 714,000 cells from 126 women, highlighting 12 main cell types and 58 cell states.

“We were able to take advantage of many technologies to define, in a very detailed and careful way, all the different cell types and cell states in each of the major areas of the breast.. We hope this tool will be very useful for anyone studying breast cancer and other diseases such as mastitis, as well as breast development or lactation failure,” says Nicholas Navin, Head of the Department of Systems Biology at the MD Anderson Cancer Center at the University of Texas, whose researchers are leading the study with the University of California at Irvine and the Baylor, Texas, School of Medicine.

“Until now there were approximations, that is, it was not such a large number and not in such a systematic way, but the technology to be able to genomically analyze a cell or a very specific cell subtype has been developed for a few years. It is an expensive technique, quite laborious and requires very powerful computer analysis. But we still need to be able to take him to the clinic,” says Alberto Orta, an oncologist at MD Anderson Cancer Center Madrid.

• The largest human cell atlas to date has been published
• A detailed cellular atlas of endometriosis is developed
• Developed and defined the cell map of the human uterus

The Human Breast Cell Atlas is part of the global Human Cell Atlas consortium supported by the Chan Zuckerberg Initiative (CZI), which uses the latest technologies to generate cellular reference maps for every organ system in the human body.

The human body has around 200 different cell types, 12 of which are found in breast tissue.. Previous studies on breast tissue focused primarily on epithelial cells, which are known to give rise to cancer, but non-epithelial cell types have not been studied in depth using genomic approaches.. New technologies have allowed researchers to perform a very detailed classification of these 12 cell types in the breast: three types of cells: epithelial, lymphatic, vascular, myeloid, T cells, B cells, adipocytes, mast cells, fibroblasts, and perivascular cells.

Mapping techniques have allowed researchers to look at the protein and RNA composition of samples to understand how and where different types of cells are found.. Using these techniques, they have been able to determine the composition of known cell types and new cell states in the four main regions currently known in the breast: the lobular milk-producing areas (mammary glands), the milk ducts that transport milk, the connective tissue composed of fibroblasts and areas or adipose tissues.

Large number of 'natural killer' cells

The researchers were surprised to see that 16.7% of all cells found in normal breast tissue were made up of immune cells, including the three main types: myeloid, 'natural killer' (NK) T cells, and B cells (they thought they would find few immune cells in normal tissue). They also found an unexpectedly high number (7.4%) of perivascular cells, such as pericytes.

“The breast is a tissue that has many cells, like all tissues, and one in particular is the epithelium, which are the cells that line the cavities, the ducts, they are lining cells. Most of the cancers that we call adenocarcinoma and carcinoma derive from this epithelium, which is why we have always focused on this type of cell.. However, this has changed in recent years, now it is considered as if it were a biological ecosystem in which there are different participants: we have tumor cells, but we know that there are many other entities around and coexisting, there are the cells of the immune system – that every day are more in the front line with immunotherapy treatments-, the cells of the vascular tissue, that is, of the vessels, we also have a lot of supporting tissue, fibroblasts…”, explains Orta.

The medical oncologist at MD Anderson Cancer Center Madrid adds that this concept that was not taken into account before is what is called the tumor microenvironment. “Until now, what we could do was analyze in some way what kind of very crude components appeared there in the tumor microenvironment, but what this type of Atlas or technique has allowed is to describe the different types of cells that we find in the different compartments of cell types. For example, different types of cells of the immune system that we find in normal breast tissue, different types of cells that we also find in supporting tissue, and their characteristics, so that in the future we will have the possibility of putting into context the treatments or the specific characteristics”.

Differences by age and ethnic origin

For this Atlas, researchers have collected and examined 220 breast tissue samples from 132 women who underwent breast reduction surgery or a mastectomy.. Of these, 46% were Caucasian, 41% African American, 7% Hispanic, and 6% of unknown ethnicity.. This map also takes into account individual factors such as ethnicity, age, BMI, obesity, stage of menopause, pregnancy, and number of births, providing a wealth of information for the research community.

Thus, African-American women are disproportionately affected by aggressive breast cancer subtypes, such as triple-negative breast cancer and inflammatory breast cancer, but not much is known about the causes of this disparity.. There are also significant differences in the breast tissues of women older than 50 compared to younger women, and differences in cell states that depend on the stage of menopause.

In any case, more studies are needed to better understand the functional role of many of these cellular states and focus on other factors that can significantly advance knowledge of the biology and diseases that can affect the human breast.. “To get an idea, it's like when the human genome was described. It was an important milestone, it took many years and cost a lot of money, but today we can do a feature analysis in less than a week and at a reasonable cost, we have a lot of genomes sequenced and a lot of things have been developed. Well, this is something similar, that is, it is something that in some way sows a base and that, of course, will have tremendous applicability in the future,” concludes Orta.