Murrow LM, et al., 2022

Estrogen and progesterone are hormones that play a key role in shaping breast development and are known to influence the risk of breast cancer. Most breast cancers are hormone receptor-positive, meaning they are fueled by these hormones. However, only a small portion of cells in the breast directly respond to estrogen and progesterone. This means that many of the effects these hormones have on the breast are indirect—driven where hormone-sensitive cells send messages to other surrounding cells. Although scientists understand that hormone signaling is important, they still don’t know exactly how these interactions play out at the level of individual cells in human tissue.

Additionally, researchers have struggled to explain how common life experiences—like pregnancy, body weight, or hormonal contraceptive use—change the way cells in the breast communicate and respond to hormones. Scientists have long known that pregnancy and obesity can change breast cancer risk, but the specific ways these factors alter cell behavior and hormone responses remain unclear. This study aimed to better understand how hormones affect different breast cells by mapping how those cells interact, one cell at a time.

Full-Text Journal Article PubMed

What did they study?

To better understand how breast cells respond to estrogen and progesterone, the researchers looked at the activity of individual cells from breast tissue donated by 28 healthy premenopausal women. They examined over 86,000 cells and identified the major cell types found in the breast.

The team also examined patterns of communication between these cells. By comparing tissue from women with different characteristics—such as whether they had given birth, their body mass index (BMI), or whether they were using hormonal birth control—they were able to observe how these variables influenced hormone signaling across the breast.

Samples from the Komen Tissue Bank were used to make sure that patterns related to body weight were not being confused with other factors like age or pregnancy. This group included older women who had all previously been pregnant but had different body weights. These samples helped confirm that body weight alone, separate from age or reproductive history, is linked to changes in cells that respond to hormones.

What did they find?

1. Most hormone effects in the breast are indirect. The researchers found that although only a small percentage of cells in the breast directly respond to estrogen and progesterone, these hormone-sensitive cells send signals to other surrounding cells, influencing their behavior.
2. Pregnancy dampens hormone activity. Women who had been pregnant showed reduced hormone signaling response in their breast tissue. The cells that normally respond to estrogen and progesterone were less active. These changes may help explain why pregnancy protects against hormone-driven breast cancer in the long run. This could be caused by slightly lower estrogen levels in the body, changes in blood flow or how hormones reach the cells after pregnancy.
3. Obesity reduces hormone-responsive cells. Women with higher body weight had fewer hormone-sensitive cells in their breast tissue. Even though the remaining cells could still respond to hormones, the smaller number of these cells meant that overall hormone signaling was reduced.
4. Hormonal birth control changes how breast cells behave. Women taking combined birth control pills showed signs that their breast tissue was more active in ways similar to what happens after breastfeeding. These changes happened even without the natural rise and fall of hormone levels that occur during menstrual cycles, suggesting that steady hormone exposure from pills alone can affect how breast cells function.
5. Pregnancy causes lasting physical changes in breast tissue. After pregnancy, the small glands in the breast that produce milk become shrink and more tightly packed. These changes leave less room for hormone-sensitive cells and shift the overall mix of cell types in the breast, creating a long-term effect on how the tissue responds to hormones.

Why is this study important?

It also shows that obesity alters breast tissue in different but still significant ways, reducing the number of cells that can respond to hormones. By capturing these patterns at the single-cell level, the study helps explain why some women are more protected against breast cancer than others and lays the groundwork for more personalized prevention strategies in the future.

Full citation

Murrow LM,Weber RJ,Caruso JA,McGinnis CS,Phong K,Gascard P,Rabadam G,Borowsky AD,Desai TA,Thomson M,Tlsty T,Gartner ZJ Mapping hormone-regulated cell-cell interaction networks in the human breast at single-cell resolution.. Cell systems 2022 Aug; 13 (8). PMID:35863345.