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MONDAY, June 9, 2003 (HealthDayNews) -- Individual breast cancer cells may escape from the original tumor and travel to other parts of the body at an earlier stage than originally thought.
This finding from German researchers, which appears in this week's issue of the Proceedings of the National Academy of Sciences, could change the way health experts think about approaches to cancer.
"It's definitely a new paradigm," says Christos Patriotis, an associate member of the Fox Chase Cancer Center's department of medical oncology in Philadelphia. "There's always been a suspicion among scientists that advanced metastatic disease is not necessarily the same disease as the primary disease."
The classic paradigm for cancer metastasis holds that cells in the primary tumor undergo a long series of genetic changes before leaving that tumor and heading off to other parts of the body.
"So far, we have thought that probably the most advanced cell within the primary tumor will leave the primary site and found a metastasis," says study author Dr. Christoph Klein.
The new research, which focused on breast cancer but could apply to other types of cancer, raises the possibility that there are actually two different routes by which the disease can spread: the classic one and this entirely new way.
The idea could affect how doctors find metastatic cancer, which is cancer that has spread from one part of the body to another.
"Many people are using primary tissue from the original breast tumor and exploring it, looking for indicators of spread. And what this [the new research] says is the changes you find in that breast tissue cancer may, in fact, not be the full changes that you get when there's metastatic disease," says Dr. Clifford Hudis, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York City.
"The genetic changes that scientists have been looking for may not occur until late in the game, so don't be surprised when your preliminary looks at genetic instability don't yield impressive results. It is really interesting and it's not what anybody expected," Hudis adds.
The new concept also has implications for treatment.
"In most of the cases where there is a very clear in situ disease [one that has not spread], then the strategy is to have minimum surgery and treatment, as little as necessary," Patriotis says. "You treat the primary disease and ignore any other disease that has already escaped because you believe there is no such disease."
But in breast cancer and also prostate cancer, there have been cases where the initial cancer is seemingly "cured," yet a secondary tumor develops years later. "We see cases where we treat the primary disease, we think that we are clean and out, then three to four years down the line we get relapses with metastatic disease," Patriotis explains.
Ideally, the study authors say, treatment should take into account any differences between primary tumors and cells that have dispersed.
"We think if you want to perform adjuvant therapy you have to know the characteristics of the target cells," Klein says. "Clinicians are administering drugs to patients to kill these [metastasized] cells but they don't know anything about them. That was why we decided to investigate these cells."
Klein and his colleagues at the Institut fur Immunologie, Ludwig-Maximilians Universitat in Munich, took bone marrow from breast cancer patients and analyzed individual cells that had migrated to the marrow from the primary tumor. The sample group included both patients whose cancer had spread or metastasized and those whose cancer was still localized.
"We were quite surprised about the genetic findings," Klein says. "It seems that the cells leave the primary tumor very, very early. We found [the dispersed cells] had even less changes than the primary tumor, meaning they leave at an early stage of genetic development, even before the primary tumor has accumulated certain changes."
The majority of these wandering cells won't develop into a tumor, but there's always that potential.
"That's why time is against us," Patriotis says. "The longer you live and the longer you have those cells around, the higher the risk that cells will accumulate the necessary mutations and really take off to become tumors."
Which is why it's vital to find them as quickly as possible. The results of this study may lead to new clinical practices, such as sampling bone marrow even when a patient has localized disease.
"Their [the study authors'] point is that looking for genetic indicators of metastatic potential might not help us much right now because genetic changes might occur late in game," Hudis says. "We have to look differently."
There may also be a drive to find new signs of single metastatic cells in patients with early-stage cancer, Patriotis adds.
Researchers would then need to see if the drugs that are used on primary tumors will also be effective on these errant cells. "Companies that develop new therapies should try to validate whether or not their compounds can work on these cells," Klein says. "They cannot rely on the data of the primary tumor."
Investigations are already under way to see if the same process is at work in other cancers, such as prostate cancer, Klein says.
More information
The National Cancer Institute has more on metastatic cancer and on breast cancer.
