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    Early Diagnosis - Then What?
    A Method to Predict Recurrence May Be Here

    The pink ribbon campaigns to increase awareness of breast cancer and educate women about the benefits of early detection are working. The ability to diagnose cancer in its early stages has never been better.

    With cancer screening becoming more accepted, as many as 80 percent of those diagnosed with cancer today are told that their cancer has been detected early and can be removed.

    Yet among those with early-stage cancer, about half will experience a recurrence (relapse) following surgery because microscopic cells have spread to other areas (micro-metatastic cancer). In breast cancer, this rate is slightly lower if the cancer is caught in the earliest stage.

    This creates a dilemma for patients and oncologists who must decide whether to decide against post-surgical treatment, thereby running the risk that the cancer will return, or undergo chemotherapy and radiation treatments that have serious side effects and may be unnecessary. Clinicians will usually recommend the treatments, erring on the side of caution.

    If half of those with early stage cancer will experience relapse, that means about half will either be overtreated - or undertreated - because there are no good methods for identifying which cancers will come back.

    The decision of whether to undergo treatments is difficult for the doctors and the patient. If there is a 50 percent chance that the cancer will come back, can you pass up treatments that might prevent it? On the other hand these treatments are highly toxic - they are designed to kill cells - they don't care if the cells are cancer or heart tissue.

    If a decision is made not to treat a patient who has potentially micro-metatastic disease, the opportunity to destroy the tumor in its early stage, when only a few tumor cells exist, is lost. When the cancer reaches detectable levels in these patients it is generally difficult to completely remove it.

    The decision to treat someone who is not at risk of relapse from micro-metatastic disease means being subjecting healthy cells to the debilitating effects of chemotherapy.

    Depending upon the chemotherapy used, these patients are unnecessarily subjected to adverse long-term consequences such as mutated DNA, heart complications, secondary cancers, and premature aging.

    Can Apoptosis Proteins Predict Survival in Early Cancer?
    John Reed, MD, PhD, is the President and CEO of the Burnham Institute, La Jolla, CA, where he leads a team of some 40 researchers who are examining diagnostic testing methods aimed at pinpointing the likelihood of cancer relapse among patients with early-stage breast, colon or prostate cancer.
    Dr. Reed presented the status of their research during his presentation entitled, "Can Apoptosis Proteins Predict Survival in Early Colon Cancer?," at the 55th Annual Meeting of the American Association of Clinical Chemistry (AACC).

    Background and Research
    When tumors arise, they often develop defects in the machinery that controls the lifespan and death of cells (the apoptosis machinery).

    These tumors also exhibit certain behaviors that make them resistant to cell death mechanisms. If a normal cell that grows in either the breast, color or prostate detaches from where it grew, it will try to circulate in the blood or lymph and go elsewhere.

    Normal cells cannot do this. These cells die, because their survival is dependent upon the signals they receive from the organ where they belong. A normal breast tissue cell cannot move to another place and continue to grow.

    Cancer cells have defects in the apoptosis machinery, that signals the cell to die. They continue to flourish, despite being detached from their host organ.

    They survive in the circulating blood and lymph fluids and lodge in other organs where they continue to grow and multiply - making copies of themselves with the faulty mechanism and interfering with the normal cells in these organs.

    Understanding how apoptosis works is the focus of the Reed lab. He and his colleagues are researching antibody-based tests using immunological methods and apoptosis biology to examine the proteins encoded by various genes related to breast, prostate and colon cancer.

    Specifically, they are applying immuno-diagnostics to patient tumor specimens using samples of tumors that have been saved for research.

    This retrospective approach allows them to correlate their results with the actual patient outcomes from samples provided nearly a decade ago. They have a tumor sample from a patient and know that the patient survived and was cancer free. They also have tumor samples where they know that the tumor came back... the patient had a recurrence.

    Based on that knowledge, they have identified those that look promising and are now using them on other patient cohorts to ensure that the results are reproducible.

    One group that they are studying is comprised of 120 patients diagnosed with early stage II colon cancer which had been removed with margins free of tumors, had received no other therapy, and were clinically followed for eight years.

    Approximately half of these patients relapsed and eventually died.

    Their original tumors were obtained and have been used to conduct 50-60 different types of experimental tests. Of this large number of potential tests, four have been identified that, when used in certain combinations, predict with 98 percent accuracy who will relapse and who will not.

    Conclusions
    The fruits of the genome, coupled with tests like those now being identified, mean that in the foreseeable future laboratories will be able to identify molecular and genetic signatures in cancers that will allow physicians to know which diseases are more aggressive and have acquired metatastic capabilities, and which tumors have not.

    This information will result in better clinical decisions about what the optimal therapies are for those diagnosed with early stage breast, colon and prostate cancer.

    The American Association for Clinical Chemistry (AACC) is the world’s most prestigious professional association for clinical laboratorians, clinical and molecular pathologists, and others in related fields. AACC’s members are specialists trained in the areas of laboratory testing, including genetic disorders, infectious diseases, tumor markers and DNA. Their primary professional commitment is utilizing tests to detect, treat and monitor disease.

    Sources: American Association for Clinical Chemistry (AACC) (Newswise)

     

    Elsewhere on the Web:

    Treating Breast Cancer Recurrence A Complex Decision

    Breast Cancer: Treating Recurrence

     

     

    July 22, 2003

    Last updated June 30, 2006

     

     

     

     

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