Kang T, et al., 2020

Scientists have known that breast tissue near a tumor—while it may look completely normal under a microscope—can behave very differently at the molecular level. Even in breast tissue that looks healthy, scientists found differences in how certain genes behave. Genes carry instructions for how cells grow and function, and in some cases, they can send signals that make it easier for cancer to return or spread.

One of these gene activity patterns—called the "Active" type—has been linked to a higher chance of breast cancer coming back. This pattern shows up in areas near tumors and includes signals related to inflammation, healing, and how cells move around—processes that may help cancer grow or spread in the body.

These studies raised a key question: is this risky pattern something that only happens because of a nearby tumor? Or could it already be present in the healthy breast tissue of women who haven’t been diagnosed with cancer?

A previous study looking at normal tissue near breast tumors found that the Active pattern showed up more often in areas that had high amounts of fat. This raised the possibility that certain kinds of activity associated with fat cells inside the breast—not just a nearby tumor—might help create conditions that allow cancer to grow. But no one had tested whether this same pattern could be found in healthy women with no signs of disease.

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What did they study?

The researchers looked at breast tissue donated by 151 healthy women with no history of breast cancer. These women were not undergoing treatment or showing signs of any breast issues. Most were considered low risk based on a standard tool used by doctors to estimate breast cancer risk (called the Gail model).

To understand the activity inside this "normal" tissue, researchers examined two things:

1. Tissue composition — How much of the tissue was made up of fat cells versus other cells like connective tissue and the cells lining breast ducts.
2. Gene activity — What types of signals the cells were sending out. They looked at patterns in the way cells were functioning at a molecular level, similar to reading a cell’s instruction manual.

   By comparing these signals to those seen in earlier studies, the researchers determined whether each sample had the Active phenotype or not. The main goal was to find out how often this risk-related pattern appears in healthy women’s breast tissue—and whether it shows any of the same features found in tissues that help cancer grow.

What did they find?

1. Over half of the healthy women had the same active gene activity pattern seen near breast tumors. These women had no signs of disease, which suggests this risk pattern can exist long before cancer ever develops.
2. Women with this pattern were more likely to have a higher estimated breast cancer risk. Even though none of the participants had cancer, those with the Active gene pattern scored significantly higher on the risk-assessment, tying the molecular pattern to increased risk.
3. Tissue with the Active phenotype had a very different cell makeup. It contained a much higher proportion of fat cells, larger individual fat cells, and fewer of the cells typically found in healthy breast ducts and supporting tissue.
4. These fat cells were biologically active in ways that could promote cancer. The cells sent out signals tied to inflammation, tissue remodeling, and growth—all of which are known to create an environment where tumors are more likely to form or thrive.
5. These changes weren’t due to body weight or age. The women with the Active phenotype didn’t differ in terms of body mass index or age compared to those without it. That means this risk pattern isn’t simply a result of obesity or aging—it may be a distinct biological state.

Why is this study important?

This study shows, for the first time, that a risky gene activity pattern often seen near breast tumors is common in healthy breast tissue too—especially in tissue with more and larger fat cells. This means some women may carry a hidden biological environment that makes it easier for cancer to take root, even if everything looks normal on a mammogram or biopsy.

The findings offer a new way to think about breast cancer risk in terms of activity happening quietly inside the tissue. These results mean that future screening or prevention efforts might one day focus on identifying these early signals.

In the long run, this could help doctors find women at higher risk earlier, even when traditional tools don’t flag them—and open the door to more personalized approaches to breast cancer prevention.

Full citation

Kang T,Yau C,Wong CK,Sanborn JZ,Newton Y,Vaske C,Benz SC,Krings G,Camarda R,Henry JE,Stuart J,Powell M,Benz CC A risk-associated Active transcriptome phenotype expressed by histologically normal human breast tissue and linked to a pro-tumorigenic adipocyte population.. Breast cancer research : BCR 2020 Jul; 22 (1). PMID:32736587.