Whole Living Guide >Investigation

Are We Getting Better at Finding Ovarian Cancer?
By Gail Zyla • Illustrations by Caitlin Kuhwald

Mary Ann Beall had a hunch. A month after receiving a clean bill of health from her gynecologist in September 1989, Beall, of McLean, Virginia, noticed some leakage of vaginal fluid. “I thought it didn't seem right,” says Beall, who was 45 years old at the time. “The doctor kept reassuring me that it was nothing, but I thought I’d better pursue it.” The possibility of cancer, she says, was in the back of her mind.

So Beall went back to her doctor, who obligingly ran some tests and discovered that she had an enlarged ovary and a polyp in her uterus. But during the operation to remove the polyp, Beall’s surgeon found a much more serious problem: cancer in both ovaries and both fallopian tubes (which connect the ovaries to the uterus). The surgeon delivered the news to Beall's husband before she woke up, and her husband gave the go-ahead to remove the cancerous organs and her uterus immediately.

“I was in good hands,” says Beall, who credits her doctor with taking her hunch seriously. “If I hadn't had that symptom, I wouldn't be here today.”

Indeed, Beall knows all too well how difficult it is to detect ovarian cancer. It took numerous doctor visits before her mother was diagnosed with ovarian cancer in 1966, at the age of 50. Sadly, by the time Beall's mother got the diagnosis, she had late-stage cancer. She died a year and a half later.

Just as tragic is that today—more than 30 years later—this type of scenario is still the rule rather than the exception. More than half of women with ovarian cancer aren’t diagnosed until it has spread to other organs in the abdomen (stage III); or to the lung, liver, or lymph glands of the neck (stage IV).

At stage III, a woman's odds of living another 5 years are about 20 percent; at stage IV, the odds drop to 5 percent. But if the disease is caught at stage I, when still confined to the ovaries, a woman has a 95 percent chance of being cured.

Why is the disease so stealthy? For starters, the symptoms, typically lasting for weeks on end, are often vague. These include abdominal pain, bloating, gas, fatigue, fever, frequent urination, menstrual irregularities, backache, leg pain, and pain during intercourse. When women come in with such complaints, many doctors don't think of ovarian cancer.

Some women with ovarian cancer have no noticeable symptoms. When Eileen Jackson of New York City was having difficulty conceiving in 1984, her doctor felt something abnormal during a pelvic exam. A sonogram showed what appeared to be a cyst, and Jackson’s doctor recommended removing it surgically.

Jackson, who was only 27 at the time, recalls that, “Going into the operation, I didn't have a clue it might be cancer”—and neither did her doctors. When they discovered a malignant ovarian tumor, she was told afterward, "You could have knocked every doctor over with a feather.” She adds, “When I woke up, I had had cancer and a hysterectomy. Ovarian cancer really knows no age.”

Stalking the Stalker
Scientists have yet to develop an effective screening tool for the disease. The only blood test routinely used to help diagnose ovarian cancer measures the level of a protein called CA-125, often elevated in women with ovarian cancer. But the test yields so many misleading results that it cannot stand alone as a screening tool. Consider that only 40 to 50 percent of women with stage I ovarian cancer have high CA-125 levels, while many women with benign conditions, including pregnancy, check in with a high CA-125. What's more, because the ovaries lie deep in the pelvis, small tumors on their surface are difficult for even seasoned doctors to feel during a pelvic exam.

Granted, doctors can often get a sense of the size and consistency of the ovaries during a transvaginal ultrasound scan, a several-hundred-dollar procedure performed by inserting a metal probe into the vagina.

Still, an ultrasound can't reveal for sure whether a mass is benign or malignant. Often, the next step is to take a biopsy of the mass, which, like any surgical procedure, is invasive, uncomfortable, and carries some risk. And the expense varies, depending on a person’s health insurance coverage.

In Great Britain, researchers have launched a 10-year study of 200,000 women. They want to find out whether an annual CA-125 blood test or a transvaginal ultrasound would be useful for screening all postmenopausal women over the age of 50 for ovarian cancer.

“CA-125 is always criticized for not being sensitive enough to pick up early
disease,” says Steven Skates, PhD, the Harvard Medical School professor who helped design the study. “Each woman may have her own individual baseline or ‘normal’ CA-125 level,” he says. “If we track the changes in that level over time, and see a significant increase in her CA-125, it may serve to identify her early ovarian cancer.”

The study’s results won’t be available for another eight years, in 2011.

In the meantime, researchers in the United States are conducting clinical trials to find other, reliable signs or “markers” of early-stage ovarian cancer.

One is an ongoing project of the National Cancer Institute's (NCI) Early Detection Research Network. The driving force behind this study is the fact that cancerous tumors have certain genes that produce unique amounts of proteins, fats, and other substances that may show up in the blood and urine in the early stages of cancer.

For the trial, researchers are collecting blood samples from women with ovarian cancer before they undergo surgery. Then, using a relatively new technique called micro-array technology, they analyze the substances in the blood “in one fell swoop,” says Dr. Skates, one of the NCI investigators.

The technology allows researchers to measure dozens of different blood substances all at one time. In this way, they can figure out which ones would be useful markers for ovarian cancer. They’re looking for patterns in women with early-stage ovarian cancer. For instance, they may find that substances X, Y, and Z are always elevated by a certain percentage. By homing in on these substances in the blood, scientists might be able to develop a blood test for those markers to help screen for ovarian cancer. Such a blood test could then be used to test large groups of women for the disease.

David Fishman, MD, director of the cancer early-detection program at Northwestern University, is spearheading the study of another promising diagnostic tool. It’s known as the “ovarian Pap test.”

For this procedure, a doctor collects cells from the surface of the ovary through a tube called a laparoscope. A smattering of cells are “brushed” from the ovary and then analyzed to try to detect precancerous cells, the way the Pap smear checks for abnormal cells on the cervix. Scientists are still working out the bugs in the analysis of which ovarian cells may be precancerous. (Bear in mind that the actual Pap test now in widespread use only checks for cervical cancer, not ovarian cancer.)

Another early area of experimentation involves a substance in the blood called lysophosphatidic acid (LPA). Some small studies suggest that LPA levels are significantly elevated in women with all stages of ovarian cancer, even stage I disease. To see whether this is true in large groups of women, seven major medical centers are currently conducting clinical trials testing LPA levels.

Though current research into early detection for ovarian cancer holds promise, the tests are still perhaps years away. LPA and the ovarian Pap smear “are not ready for prime time,” says M. Steven Piver, MD, an oncologist at the State University of New York in Buffalo. And Dr. Skates admits that micro-array technology “is a promising idea that has yet to show its full potential.” But as research continues, patients can get involved in ongoing clinical trials that point to the future.

Until early-detection methods are perfected, experts say the best thing a woman can do to hedge her bets against late-stage ovarian cancer is to be aware of the symptoms and to know her risk. (See sidebar: “Who is at Risk?”)

Dr. Piver and other experts recommend that women with a family history of the disease begin getting pelvic exams, transvaginal ultrasound tests, and CA-125 readings twice a year, beginning as early as age 25. While we wait for the British study results, high-risk women might want to track their own baseline CA-125 level to see if the levels rise sharply from one year to the next—a possible signal of cancer.

In addition, women who experience persistent symptoms of ovarian cancer need to alert their doctors. “Women with vague symptoms should not think they're crazy,” says Dr. Piver. “And doctors need to take women with vague symptoms seriously and consider the possibility of ovarian cancer.”

As for existing detection methods: When undergoing transvaginal ultrasound, women should be aware that the test is only as good as the professional who performs it. Make sure your doctor has experience doing the test routinely and that he or she uses state-of-the-art equipment, including color Doppler imaging. If a cyst is found on an ovary, color Doppler imaging allows a doctor to measure the blood flow to the cyst. This is key, because benign cysts resist blood flow more than cancerous tumors. “If resistance to blood flow is low, it hints that it's a malignant tumor,” says Dr. Piver.

For women like survivor Mary Ann Beall, refinements in early detection can’t come soon enough—she has three daughters, all in their twenties.

“I hope the testing will get better,” she says. “I saw how horribly my mom suffered. I was horrified when it happened to me, even though I tried to be vigilant about my health.” Beall had visited her doctor every six months before discovering she had cancer. “I don't want to live to see my daughters have something like this.”

Gail Zyla, MS, RD, has been covering health issues for more than a decade. A registered dietitian, Zyla's articles have appeared in Consumer Reports On Health, Parenting, Redbook, and Reader's Digest, among other publications.

Sidebar
Who is at risk?

Each year ovarian cancer claims the lives of more than 14,000 women, making it the deadliest of the cancers that affect the female reproductive tract. Until more effective screening tools are found, experts say that knowing your risks and being aware of the symptoms are the best ways to stay ahead of late-stage ovarian cancer. These factors raise the risk of developing the disease:

Family history
Having two or more relatives (mother, sister, daughter, aunt, grandmother) from either side of the family who have had ovarian cancer increases a woman’s risk of getting the disease as much as 50 percent. The risk is greatest if the relative’s cancer struck before menopause, or if other family members have suffered breast, endometrial, colon, rectal, or pancreatic cancer.

Breast cancer
Breast cancer doubles a woman’s risk of ovarian cancer, in part because inherited BRCA1 and BRCA2 gene mutations increase the chances of developing both diseases.

Talcum powder
Some studies suggest that use of talc (baby powder) in the genital area causes a slightly increased risk of ovarian cancer. A possible explanation: talc used to harbor asbestos—a known carcinogen—and genital exposure gave the chemical entree into a woman’s ovaries through the vagina. The jury is still out on the theory. Asbestos has been banned from talc since the 1970s.

Reproductive history
Menstruating before age 12, not bearing children, having a first child after age 30, or going through menopause after age 50 all appear to increase the risk of ovarian cancer.

Diet
A diet high in fat, particularly fat from meats and other animal sources, has been linked to an increased risk of ovarian cancer.

Fertility drugs
Though controversial, some research suggests that prolonged use of fertility drugs (Clomid, Milophene, and Serophene) predisposes a woman to ovarian cancer. That risk seems to be pronounced in women who fail to become pregnant when using the drugs. It’s not clear whether it’s the drugs themselves or the underlying condition causing infertility that raises the risk.

To find out about joining a clinical trial on early detection of ovarian cancer, call the National Cancer Institute’s Cancer Information Service at (800) 422-6237.