Dirks RC, et al., 2020

Doctors and scientists are always looking for ways to detect cancer earlier and predict how patients will respond to treatment. One promising strategy is to find biomarkers—specific molecules in the body that can signal cancer is present or developing. However, discovering reliable biomarkers for breast cancer has been especially difficult. A major reason is that many studies compare tumors to nearby tissue that appears normal. But this so-called “normal adjacent tissue” (or NAT) isn't truly healthy. Because it sits so close to the tumor, it’s often already affected by the cancer, making it a poor choice for understanding the characteristics of truly healthy breast tissue.

This study explores how genetic ancestry and tissue type—whether it comes from a tumor, nearby tissue, or healthy breast—affect the levels of a possible biomarker called MMP7. MMP7 is a protein that plays a role in inflammation and in breaking down and rebuilding tissue, which can affect how the breast changes or responds to damage or disease. The researchers used tissue samples donated by healthy women through the Komen Tissue Bank and compared them to tumor and NAT samples collected from breast cancer patients.

Full-Text Journal Article PubMed

What did they study?

The research team collected breast tissue from three types of sources:

1. Healthy breast tissue from women with no history of cancer.
2. NAT samples, which are non-cancerous but taken from areas close to a tumor
3. Tumor tissue from women with breast cancer.

   They focused specifically on a type of breast cell called the luminal progenitor cell, which is believed to be the starting point for many types of breast cancer. The researchers used techniques to identify which genes were more active in NAT and tumor samples compared to healthy. One of the genes they focused on, MMP7, was examined further using both genetic and protein analysis techniques.

   They also looked at how genetic ancestry—specifically African American (AA), European American (EA), and Hispanic backgrounds—affected MMP7 levels.

What did they find?

1. Genes related to inflammation were more active in tissues next to tumors and in tumor cells than in healthy breast tissue. The researchers found that 26 specific genes were more active in both NAT and tumor tissue compared to healthy breast tissue. These genes formed a network related to inflammation, suggesting that even though NAT is not cancerous, it has already begun to change in ways that may support cancer growth.
2. MMP7 and other inflammation-related genes were more active in tumor and NAT tissues than in healthy tissue. They found that MMP7 was more active in tumors than in NAT, and both had higher levels than healthy breast tissue. This again suggests that NAT isn’t truly “normal” and may already be showing early signs of cancer-related changes.
3. MMP7 protein was found in higher levels in tumors, especially among European American women. The body first uses genes to send out messages (like instructions), and then turns those messages into working parts—proteins that do jobs in the body. The researchers found that tumors not only sent more messages for MMP7 but also had more of the MMP7 protein itself. This adds strong evidence that MMP7 might be involved in how breast cancer grows. In NAT samples, though, the levels of gene messages and actual protein didn’t always match. This mismatch between gene activity and protein levels suggests that gene-level findings alone may not be enough to identify reliable biomarkers.
4. Genetic ancestry affected MMP7 levels. For women of European ancestry, MMP7 levels were higher in tumors compared to nearby tissue or healthy breast tissue. African American samples showed mixed results, and Hispanic samples generally had lower MMP7 levels in tumors, but in both cases, the small number of samples makes it hard to draw strong conclusions.

Why is this study important?

Biomarkers matter because they help doctors find cancer, understand how serious it is, and choose the best treatments. They are like clues in the body that can show if something is wrong or changing. But to be useful, biomarkers need to be accurate and work well for everyone. This study also found that a person’s genetic background can affect how biomarkers appear, meaning a test that works for one group may not work the same for another. Thus, the study shows the importance of using truly healthy tissue and considering people’s backgrounds when trying to find better ways to detect and treat breast cancer.

Full citation

Dirks RC,Burney HN,Anjanappa M,Sandusky GE,Hao Y,Liu Y,Schmidt MC,Nakshatri H Breast Heterogeneity: Obstacles to Developing Universal Biomarkers of Breast Cancer Initiation and Progression.. Journal of the American College of Surgeons 2020 Jul; 231 (1). PMID:32311464.