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New insight into aggressive breast cancer could drive treatment choices

Breast tumors that are both estrogen-receptor (ER)- and HER2-positive are typically slow-growing, while ER-negative, HER2-positive cancers are more aggressive. Now, researchers at Baylor College of Medicine have discovered a pathway by which ER/HER2-positive breast tumors can transform into more aggressive, ER-negative-like subtypes—a discovery they believe could eventually change the way breast cancer is tracked and treated.

Using a mouse model that allowed them to study breast cancer progression, the Baylor team discovered there are two types of ER-negative tumor cells: The first is fast-growing but not so quick to metastasize, while the second originates from ER-positive cells and is fast both to grow and to metastasize. They published their findings in the Proceedings of the National Academy of Sciences.

The researchers started by setting up mouse models with equal amounts of ER-positive/HER2-positive cells and ER-negative/HER2-positive cells. They watched the cells over time using a red fluorescent protein to track all cells arising from the ER-positive cells. That’s how they discovered that some tumor cells lost their estrogen receptors over time. What’s more, the ER-negative cells that emerged were quick to grow and spread.

They went on to study the DNA of the mammary gland cells in an attempt to discover exactly what was happening to cause some cells to lose their estrogen receptors. The answer? The enzyme MAP kinase was activated differently in the cells, leading to disparities in their aggressiveness.

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