When I started out as a breast surgeon in the early 80’s, we thought that a diagnosis of breast cancer was an emergency. Time was of the essence, and you had to rush in and do a biopsy and immediate mastectomy to prevent a tumor from spreading to other organs. But that’s not the case. Since then, we’ve learned that cancer cells are shed into the blood stream early on. Even before the tumor can be diagnosed, they make themselves at home in other organs. That’s why almost all patients with early-stage tumors get systemic therapy (hormone pills, chemotherapy and/or Herceptin). We want to do our best to get rid of those cancer cells that have already moved away from the original tumor.
New techniques, called “liquid biopsies”, are now being used at the time of diagnosis. These blood tests can detect cancer cells circulating in the blood stream. However, we still don’t know if the cancer cells that are circulating in the blood are on their way to another organ, or whether they are being shed by metastatic sites that have already been established. As scary as this all sounds, it’s important to note that most circulating tumor cells do not have the skill set necessary to set up shop in another organ (metastasize).
Recently we learned that, after 20 years, Olivia Newton-John’s breast cancer has recurred. Her cancer had to have come from the initial tumor. And this may be because the bone marrow is not only welcoming to metastasis, but because the bone marrow provides a protective haven from chemotherapy and hormonal treatments, allowing cells to persist for decades.
Studies have shown that when special techniques are used, clinically undetectable bone marrow metastases can be detected in 30% of breast cancer patients with stage I, II or III cancers. And those patients with bone marrow metastases have an increased risk of recurrence.
In a recent study, researchers examined the molecular features of cancers cells in tumors that had been removed from 743 patients with lymph node-negative breast cancer who did not have chemotherapy or hormonal therapy after surgery. Based on their gene expression, the tumors were divided into four subgroups. One of the four gene expression profiles was associated with a low risk of late recurrence, while another one was associated with an increased risk of late recurrence. Most of these late recurrences were in bone. Moreover, the researchers found that the breast cancer cells made their home in a special niche where they could remain quiet and anchored.
So, what does this mean in terms of treatment? We need to see if it’s possible to evict the dormant cells from their hiding places into the blood stream at the time of diagnosis, so that they could be exposed to treatment at the time of initial diagnosis. Another approach would be to figure out how to keep the cells dormant forever, which may be how some hormonal treatments work. And in cases like Olivia Newton-John’s, maybe we can figure out how to reverse the process and put them back to sleep.