The amount of research now being done on the hows, whys, and whens of metastatic disease is staggering. This work has been made possible by a technological advance that allows scientists to analyze the circulating tumor cells and tumor DNA that can be found in the bloodstream.
Cancer cells have to develop a certain skill set to be able to break away from the tumor and sail out into the bloodstream to find a new home. But not all of the cells that develop these skills are alike. You could think of them as bees leaving a hive. Some will be aggressive and fight to set up a new colony (new metastases). Others will die en route to their destination. And some will happily pollinate flowers and cause no problems.
We initially thought that the new technology would make it possible to see whether any of the circulating tumor cells/bees were aggressive and to identify the weapons/mutations they had. Having this information would then make it possible for doctors to choose the treatments that would target these specific mutations, an approach sometimes referred to as precision medicine.
Now, like virtually everything about cancer, it’s more complicated than we originally believed. Studies that used the new technology to compare a woman’s primary tumor to her metastatic sites found that the cells in a metastatic site are not always the same as the original tumor. Making matters even more complicated, within metastatic sites there can be cells with different types of mutations. Some may be sensitive to estrogen, others may not. Some may be HER2-positive and others may be HER2-negative. And so on.
Why does this happen? The thinking is that cells that develop the skill set they need to move to other parts of the body also develop skills/mutations that make it more likely they will survive in certain parts of the body. So, one aggressive bee/cell may have mutations that allow it to set up a colony in the liver while another might have the mutations that help it thrive in the lung. It’s also possible that the lung or the liver might more readily attract certain types of cells.
This, in turn, raises a new set of questions: What happens if you kill one type of tumor cell—say, those that are HER2-negative? Will the HER2-positive cells that might have existed alongside the HER2-negative ones become more powerful?
We don’t yet have all the answers. But we do know that we can no longer assume that all metastatic sites will be just like the original tumor or even like each other. This means we will need to monitor circulating tumor cells and, when possible, biopsy metastases in women with advanced disease in order to keep up with how their cancer is changing and determine the best way to treat it.