March 5, 2004
Stalking a stealthy disease: Hunting early warning signs in ovarian cancer
Samuel Mok, MD, and Daniel Cramer, MD
Common sense (and years of research) tells us that any illness, when caught early, has a greater chance for a cure. Early detection is particularly crucial when treating cancer. But with ovarian cancer, the initial physical symptoms are vague and screening tools nonexistent. As a result, it's often diagnosed at an advanced stage and has the highest mortality of all cancers of the female reproductive system.
Researchers from Dana-Farber and Brigham and Women's Hospital in conjunction with Massachusetts General Hospital (the three hospitals comprise Dana-Farber/Partners CancerCare — DF/PCC) are trying to change this with funding assistance from the National Cancer Institute's Early Detection Research Network (EDRN). They are sorting through cancer cells and patient samples in hopes of finding distinctive proteins - called biomarkers - that are elevated in blood or urine and signal the presence of ovarian cancer in its earliest stages.
"There is only one tumor marker in use for ovarian cancer today, CA 125, but it has never been shown to improve survival rates when used as a screening tool," says Ross Berkowitz, MD, director of gynecologic oncology services at the Gillette Center for Women's Cancers at Dana-Farber (part of Dana-Farber/Brigham and Women's Cancer Center). "It produces false negatives because a large percentage of women who have early-stage ovarian cancers register normal levels of CA 125, a protein found in blood, when tested."
The CA 125 test is valuable for monitoring the treatment of women already diagnosed with ovarian cancer; a decrease in levels means they are responding to therapy. But Dr. Berkowitz emphasizes that for the average woman, routinely measuring CA 125 is pointless. Elevated levels in a blood test may result from other types of cancer or from noncancerous conditions, including endometriosis, pelvic inflammatory disease, peritonitis, pancreatitis, liver disease, or any condition that inflames the pleura (the tissue that surrounds the lungs and lines the chest cavity). Menstruation and pregnancy can also cause CA 125 to rise.
Sometimes referred to as a silent killer, ovarian cancer accounts for only 4 percent of women's cancers - yet it is the fifth leading cause of cancer death among women in the United States, with a mortality rate of 14,300 annually. "Many patients are anxiously awaiting the identification of accurate markers and asking when we can use them as true screening tests," says Daniel Cramer, MD, principal investigator on the EDRN Project and a gynecologist at Brigham and Women's and DFCI. "That's our goal, but unfortunately it's still a long way away, as the process is time-consuming, labor-intensive, and costly. We have a mammoth task: finding the appropriate individual marker or combination of markers among the thousands of proteins in cells that best distinguish who has ovarian cancer and who does not."
To search for biomarkers, researchers obtain specimens of blood, urine, and/or tissue from women who are having exploratory surgery for possible ovarian cancer. It is important to get samples before a tumor is removed because protein levels in the blood and urine change after the operation. Specimens from early-stage ovarian cancer have been difficult to acquire, as most patients are in later stages of the disease when diagnosed. But over the past four years, in collaboration with Brigham and Women's and Mass General, a valuable bank of serum, urine, and tumor specimens - including samples from women with early-stage disease - has been built up.
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