To determine what type of breast cancer you have and how it should be treated, your tumor is tested to see if it has hormone receptors (ER and PR positive or negative) and if it overproduces the HER2 protein (HER2 positive or negative).
We’ve been doing this type of tumor testing for decades and have come to rely on it extensively. But as we learn more about cancer, it’s become clear that tumors are not a single entity.
Researchers using new technologies to analyze different parts of the same tumor have shown us that different pieces of a tumor can contain different mutations. These studies suggest that tumors have a dominant type of cancer cell, but also include minor colonies that have other types of mutations. In other words, most of the tumor could be ER/PR-positive and HER2-negative but there may be some cells that are ER/PR-positive and HER2-positive.
Metastatic sites can differ from the original tumor too. This is why doctors try to biopsy new metastatic sites whenever possible to see whether they are the same as the original tumor or if they have changed.
New technologies also make possible liquid biopsies–blood tests that can capture and analyze circulating tumor cells and DNA in the blood. Studies that have used these tests have previously demonstrated that there are tumor cells with different subtypes are circulating in the blood. A recent study published in Nature on Sept. 1, 2016, showed something new: not only are there different subtypes, but cancer cells can change back and forth from HER2-positive to HER2-negative.
The researchers found that 84% of women whose original tumor was ER/PR-positive and HER2-negative had acquired HER2-positive circulating tumor cells after multiple courses of treatment. They also found that circulating tumor cells could spontaneously change, with HER2-positive cells producing daughter cells that are HER2-negative, and those that are HER2-negative producing daughter cells that are HER2-positive
It’s possible that cancer treatments influence how tumor cells change. For example, treatment with hormone therapies like tamoxifen or an aromatase inhibitor may work better in the cells that are only hormone sensitive than in the ones that are ER/PR-positive and HER2-positive. This could be one reason why a woman on hormone therapy who was initially HER2-negative may get a recurrence that is HER2-positive. Other mutations in the cancer cells undoubtedly play a role as well.
Right now, a lot of researchers are trying to figure out how to use this new knowledge to benefit patients. It is important, however, to point out that the whole area is still a moving target. Learning that cancers are not just one subtype is interesting, and may give us insights into why some patients have a recurrence. It may prove especially beneficial for women and men with metastatic breast cancer. If you have the opportunity to participate in a clinical trial that includes analyses of circulating tumor cells, by all means consider taking part. This is certainly research worth watching.