Researchers from the Garvan Institute of Medical Research have determined there are two different types of triple-negative breast cancer (TNBC), and one is far more aggressive than the other.

The difference lies in where the cancer originates. The scientists found that TNBC can start in specialized cells or in stem cells. Those that start in specialized cells generally have a better prognosis. 

TNBC is more deadly when it starts in stem cells, which are able to differentiate into any other type of cell. Since stem cells can easily multiply and spread, this type of cancer leads to a poorer outcome. 

The study revealed that the “inhibitor of differentiation 4” (ID4) gene controls whether or not a stem cell turns into a specialist cell. High levels of ID4 are found in about 50 percent of all TNBC cases. Turning off ID4 in a stem cell turns on genes that determine cell specialization, which stops tumor cells from dividing.

Another significant finding is that when researchers blocked ID4, estrogen receptors and other genes associated with better-prognosis breast cancer were switched on. This could lead to new treatment options for a type of breast cancer that currently has no targeted treatment.

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Where Will Scientists Go from Here?

This is encouraging news for future treatment of TNBC. However, this was a research study, not a clinical trial. Researchers must still determine if blocking ID4 makes the cancer respond to tamoxifen, a medication used to treat estrogen-positive breast cancers. They must also figure out how to block ID4 effectively.

“There is nothing in this study that changes the current medical treatment of women living with TNBC,” Alex Swarbrick, Ph.D., the study’s lead researcher, told Healthline.    

“However, we are now working on two fronts to develop these findings into clinically relevant outcomes. Firstly, we will test whether the two subtypes of TNBC identified in this study might respond to existing drugs differently. If they do, we would test the response of women with TNBC to these drugs in prospective clinical trials, which might take three to five years to commence,” Swarbrick added. “In the second, we will attempt to develop drugs to block the action of ID4 in TNBC. It is impossible to say how long this will take, but it would be at least five years, probably more.”

Much work remains before doctors will be able to use this “switch” to affect treatment and potentially save lives. 

“The more we know about the biology of TNBC, the more tailored our treatment can be,” said Dr. Diane Radford, a surgical oncologist and breast disease specialist at the Mercy Clinic St. Louis Cancer and Breast Institute. “Dr. Swarbrick’s work on the ID4 gene and its role in cancer development is an important advance in our understanding of cancer biology.” 

Details of the study are published in the journal Nature Communications. 

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What Is Triple-Negative Breast Cancer?

TNBC gets its name from what it doesn’t have. Most breast cancers are fueled by estrogen, progesterone, or the HER-2/neu gene, alone or in combination. TNBC tests negative for all of those receptors. That’s why TNBC patients can’t take advantage of targeted treatments like tamoxifen. However, TNBC tends to respond well to chemotherapy. It can also be treated with surgery and radiation.

When compared to other types of breast cancer, TNBC has a worse prognosis and a higher rate of recurrence in the first five years. It is more likely to be diagnosed in younger women, African-Americans, or women who carry BRCA1 gene mutations. TNBC represents about 15 to 20 percent of all breast cancers. 

Five-year TNBC survivor Melissa Paskvan of Toledo, Ohio says the study gives her hope for those who will be diagnosed in the future. “TNBC survivors have been longing for a targeted therapy for some time now. This could be a game-changing discovery in how we treat TNBC in improving survival outcome in patients.”