Judith Rubel, a former marketing specialist for a Boston-area hospital, seemed an unlikely candidate for ovarian cancer. She was healthy, fit and slim. She had no family history of the disease. Besides, ovarian cancer was pretty rare — only one woman out of 59 gets the disease over a lifetime.“It never occurred to me that it could happen to me,” Rubel, who now lives in Old Saybrook, Conn., said last week.
But 6 years ago, when Rubel was 52, she was diagnosed with the cancer — which is quite survivable when found early, but often fatal when caught after it’s spread. Because there’s no good test to catch ovarian cancer, nearly three-quarters of the 25,580 women diagnosed with the illness this year will have advanced cancer by the time it is found,, as Rubel did. One of the lucky ones, Rubel, who endured surgery, chemotherapy, and a bone marrow transplant, feels well today.
But she is still worried: Will her cancer recur, and if her 33-year-old daughter gets the disease, would it be caught any earlier? Researchers believe it will. Scientists at the National Cancer Institute and a number of private companies are racing to develop blood tests to catch these well-hidden cancers early enough to treat them more successfully.
“I am optimistic that within five years there will be a truly reliable screening test,” said Dr. Beth Y. Karlan, president-elect of the Society of Gynecologic Oncologists and director of gynecologic oncology at Cedars-Sinai Medical Center in Los Angeles. Such a test “would improve survival from ovarian cancer more than any new therapy.”
Finding ovarian cancer early is a tall order, in part because at any given moment, only one woman in 2,500 has the disease. Moreover, the ideal screening test must be both highly sensitive and highly specific, meaning it should catch virtually all cancers and nothing but cancers. An ovarian cancer test that is 99 percent sensitive is pretty good — unless you’re in the 1 percent of missed cancers.
A test that is 99 percent specific sounds pretty good, too, except that the 1 percent of mistakes means 25 women of every 2,500 screened would undergo abdominal surgery — unnecessarily — to see if they really had cancer. In other words, “Many people would have to go through a dangerous procedure to find out they didn’t have cancer,” said Dr. Richard Penson, of Massachusetts General Hospital.
For women like Rubel’s daughter, already known to be at high risk, doctors use a blood test called CA-125, as well as a pelvic exam and transvaginal ultrasound, to detect cancer. But the CA-125 test, though good at detecting recurrences of cancer, is not good enough by itself to screen the general population. (A large British study of 200,000 postmenopausal women at normal risk is underway to see if screening with CA-125, combined with ultrasound, can reduce mortality from ovarian cancer.)
One of the most promising new approaches is called proteomics, the study of proteins in the cells, tissues and body fluids. Even before a tumor can be felt, some researchers have found, the tumor begins secreting a distinctive pattern or fingerprint of proteins.
Researchers “are very excited about the proteomics approach to cancer screening,” said Dr. Daniel William Cramer, a professor of obstetrics, gynecology and reproductive biology at Boston’s Brigham and Women’s Hospital and the principal investigator of the Boston component of a national effort called EDRN, Early Detection Research Network. In theory, proteomics testing could be used to screen for a wide range of cancers.In 2002, Dr. Lance Liotta, chief of the laboratory of pathology at the National Cancer Institute, and others published a paper in the journal Lancet showing that proteomics can identify distinctive patterns of proteins in the blood of women with ovarian cancer. The test was very percent effective at finding ovarian cancer, though it also falsely identified 5 percent of women as having cancer when they did not. Government researchers are now conducting a two-part study on proteomics, to determine its effectiveness at detecting ovarian cancer and its ability to predict recurrence.
In the commercial world, a number of private companies, including Correlogic Systems, Inc., of Bethesda, Md., Ciphergen, of Fremont, Calif., Fujirebio Diagnostics, of Malvern, Pa., LPL Technologies of Cleveland, and others, are also scrambling to develop and sell an ovarian cancer test — a huge potential market if they can convince women and insurance companies the test is truly reliable.
Correlogic is closest to market with its OvaCheck test, though the FDA has suggested it may need to review the product, and the Society of Gynecologic Oncologists has posted a statement on its website saying, “More research is needed to validate the test’s effectiveness before offering it to the public.”
A team from the Cleveland Clinic and LPL Technologies is working on a blood test for ovarian cancer. At Ciphergen, researchers are pursing a test for three “biomarkers” to be used in conjunction with CA-125 to detect ovarian cancer in high risk women.
“The ultimate test,” said Karlan of Cedars-Sinai, “may end up being not one test used alone,” but a combination. Despite intense lobbying from women desperate for a better test, she urged patience. “Every woman whose mom had this will want to be tested every month. But we don’t have the data yet on when, and who, to screen.”