Breast Cancer Cells May Spread Earlier Than Thought

According to the American Cancer Society one in eight American females will eventually develop breast cancer, which is the number two killer for women living in North America. Advanced screening methods have improved survival rates allowing for the tumors to be caught early. In such a stage the tumor is so small and confined that most doctors deem a simple lumpectomy to be sufficient to remove all the cancerous cells due to lack of metastasis. However, a sixteen percent recurrence rate within five years after the lumpectomy shows there is more to it than commonly thought. Now researchers at the Salk Institute for Biological Studies discovered that even these small tumors have the capability of seeding new tumors.

The early stage of breast cancer, where a tumor has not yet metastasized into the surrounding tissue, is called carcinoma in situ (CIS). This type of breast cancer is considered non-invasive. It is oftentimes located in a milk duct of the affected breast (ductal carcinoma in situ; DCIS). Until now scientists considered DCIS to be localized with only the ability to increase in size but no spread to other areas of the breast. Therefore, DCIS is considered to be a Stage 0 cancer, or "pre-cancerous" growth.

However, DCIS is still an uncontrolled growth of breast cells and requires removal of the tumor and surrounding tissue either by lumpectomy for a single growth or mastectomy for several DCISs in a breast. Radiation treatment may be recommended as well. This commonly depends on the size of the tumor and whether the pathological examination shows that the borders of the removed tissue are free of cancerous cells (clean cut). If the tumor is small and the pathological report indicates a clean cut, doctors often forego the radiation treatment. This common practice is based on the believe that the tumor had been caught in time and the removal was all that was needed to take care of this particular cancer development.

Now researchers at the Salk Institute for Biological Studies discovered, these small tumors have the capability of seeding new tumors even though common methods don't indicate metastasis. According to the study published in the Dec. 30 issue of the Journal of Cell Biology, the tissue surrounding the DCIS already contains motile cells, which can wander off along the milk ducts and cause new tumors in other areas of the breast. This indicates that a tumor can 'migrate' into other areas of the breast before metastasis can be detected through traditional methods.

For the purpose of their study, the scientists created a tissue culture model based on human cells, which resembles the tiny milk ducts present in a female human breast. Then they initiated a so-called ERK1/2 MAP kinase pathway, a signaling frequency that usually results in tumor development. Through this model, the scientists were able to observe the actual growth of breast cancer cells through all its phases. They quickly noticed significant and also unorganized cell movement. However, these motile cells were not yet able to move through the cell membrane into the surrounding tissue, which invasive cells can do.

Nonetheless, the scientists believe that this type of motility can lower the barrier for future invasive growth, as these cells would eventually be able to pass through the cell membrane. Therefore, this discovery should change treatment methods for DCIS. It also explains the high recurrence rate. The highly motile cells, especially, if already present in the tissue surrounding the tumor, put patients at risk of recurrent growth. Therefore, radiation treatment should be added as a standard treatment after a lumpectomy, regardless of tumor size and indication of a clean cut.

The scientists admit that further studies are necessary to exactly determine how these cells might trigger tumor growth. However, with live-cell imaging on the horizon, they are optimistic, they will quickly solve this part of the puzzle and be able to provide oncologists with the tools needed to identify patients with a high risk of metastasis.