Early Warning Sought For Ovarian Cancer

By Hilary Waldman

After Beatrice Robertson watched ovarian cancer cut down her former college roommate at the age of 52, the Milford woman did not hesitate to have her own ovaries - along with the rest of her reproductive organs - removed when she learned that she, too, was at high risk for the cancer known as the silent killer.

But Robertson hopes her daughters, both in their early 20s, will have a better choice.

While mammograms and Pap tests can save lives by unmasking breast and cervical cancer - other leading killers of women - in their treatable stages, there is no simple way to find ovarian cancer before it's too late.

And while a Yale researcher says he is close to marketing a simple, inexpensive blood test that can accurately detect ovarian cancer before it spreads, other experts caution that women should hold off on the celebration.

"A lot of people have been spending a lot of time and effort to develop a viable screening test for ovarian cancer," said Dr. Jonathan S. Berek, chairman of obstetrics and gynecology at the Stanford University School of Medicine in California. "And we're a long way away from that."

Part of what makes a test for ovarian cancer so elusive is really a silver lining of the disease.

It is extremely rare.

While few diseases haunt women as deeply as the threat of ovarian cancer, a vast majority of them are far more likely to suffer from heart disease, breast cancer, uterine cancer or even osteoporosis.

In the U.S., 1.7 percent of women would be expected to develop ovarian cancer at some point in their lifetimes, according to the National Institutes of Health. In comparison, 13 percent would be expected to get breast cancer.

"It's the proverbial needle in a haystack," Berek said.

That's the good news.

The bad news is that because it's so hard to catch ovarian cancer early, three of five women diagnosed with the disease will probably die within five years.

"They're terrified of it," said Dr. Molly Brewer, associate professor of obstetrics and gynecology at the University of Connecticut Health Center in Farmington. "All you have to do is read what happens to women with ovarian cancer. It's terrifying."

And thus, the race for a test.

Biomarkers

For almost two decades, scores of researchers around the world have devoted their careers to finding the biological fingerprint that will tell doctors that traces of cancerous or precancerous cells have started to invade a woman's ovaries or fallopian tubes.

Of them, Dr. Gil Mor, associate professor of obstetrics and gynecology at the Yale University School of Medicine, is thought to be the closest to what has become something akin to the Holy Grail among researchers in women's health.

"We would like to change ovarian cancer like the Pap smear changed cervical cancer," said Mor, noting that since the Pap test came into widespread use some 50 years ago, cervical cancer rates have dropped by 75 percent in the United States.

Mor is in the final testing phase of a blood test that he says can measure six proteins in the blood that change in response to several different forms of cancer. The difference between Mor's approach and previous attempts to measure tumor markers is that the Yale test does not have to wait for a big tumor to grow.

Instead, Mor's test grew out of the discovery that as a tiny group of renegade cells in the ovary begin to change from healthy to cancerous, neighboring cells respond by producing abnormal levels of certain proteins. It is those proteins that can be measured in the blood, potentially allowing doctors to catch tumors in their infancy.

To test his biomarkers, Mor's group screened blood samples from 500 women, some of whom had ovarian cancer and some of whom did not. The test accurately detected the samples from women with ovarian cancer 99 percent of the time, according to results published in the journal Proceedings of the National Academy of Sciences. It also correctly found the disease-free blood at an almost perfect rate.

Laboratory Corporation of America (LabCorp) has signed an exclusive license agreement with Yale to market the blood test, which at first will probably be offered only to women who have known risk factors for ovarian cancer. But because half of women who get the disease have no known risk factors, Mor said that it could be offered more widely after further study is conducted.

Eric Lindblom, a senior vice president with North Carolina-based LabCorp, said because laboratory tests do not require FDA approval, the test could be on the market by the end of this year. Like other new tests, he said, it initially may not be covered by insurance. But he also said the cost will probably be low enough - less than $1,000 - for some women to pay for it themselves.

No Timeline

Still, plans to market the Yale test have been met with caution in many quarters. Scientists familiar with ovarian cancer research efforts say it could be years, perhaps decades, before anybody can claim they've found the equivalent of a mammogram for ovarian cancer.

"I'm very optimistic, but I don't have a timeline," said Sudhir Srivastava, chief of the cancer research group at the National Cancer Institute. "To become a mammogram, it must show that it saves lives."

One serious limitation of Mor's test and others is that researchers do not yet understand exactly how or where ovarian cancer begins - and whether there is a precancerous stage during which abnormal cells can be detected.

Mor's group is now trying his biomarker test on blood samples taken from women several years before they were diagnosed with ovarian cancer. The results are expected within the next few months. If it picks up warning signs in those samples, its promise will be much greater, Srivastava said.

Another problem is that the ovaries are glands nestled deep within the lower abdomen and made of dense, fibrous tissue, making abnormalities difficult to see clearly with ultrasound, MRI, CT or other minimally invasive scans.

So even if a blood test turns up something suspicious, the only reliable way to rule out cancer is with surgery. In a rare disease, doctors said, that could lead to many unnecessary operations for growths that turn out to be harmless.

In the meantime, women such as Beatrice Robertson have few palatable options.

Three years ago, Robertson was diagnosed with breast cancer and learned that she carried a genetic mutation that put her at higher risk of ovarian cancer as well.

A year after her mastectomy, she opted to have her cervix, ovaries, uterus and fallopian tubes removed as a precaution. Robertson was 51, almost the same age as her dear friend who she visited in the hospital while that woman was dying of ovarian cancer.

Even after her surgery, Robertson continues to get regular blood tests for CA-125, a biomarker that can sometimes detect the presence of an ovarian tumor once it grows fairly large. But the test is notoriously unreliable and Robertson couldn't bet her life on that. Surgery seemed a drastic measure, but the only one that she thought might improve her odds.

Brewer said a test such as Mor's might be most appropriate for women such as Robertson and her daughters.

With the genetic mutation, they carry such a high risk of disease that a blood test is more likely to pick up true cancer, rather than a benign mass. And because so many high-risk women choose preventive surgery anyway, an unnecessary operation for a tumor that turns out to be benign might be a less serious misstep.

Before Robertson's friend died, a doctor told the friend's daughters - who are the same ages as Robertson's girls - to "find a husband, have your babies and have your organs removed."

Now, Robertson is wondering whether she should pass along the same advice to her daughters, now 20 and 25. With a minimally invasive test still in the distant future, she says it seems "like the only reliable thing."

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