Outsmart ovarian cancer

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Channel concern into positive action with this maximum-protection plan

"My wife Gilda was afraid of cancer all her life," recounts Gene Wilder in a public-service ad. "And even with wonderful doctors, no one discovered she had ovarian cancer until it was too late. . . ."

The ad, sponsored by a renowned cancer-treatment center, goes on to caution women: "If you have vague symptoms, like abdominal bloating, clothes that feel tight, backache and sudden fatigue, don't worry, they're normal. But if they don't go away--and especially if you have a family history of ovarian cancer--see your doctor right away."

Well intentioned as it may be, this ad sent an untold number of healthy women into a state of near panic. We know this because several of our friends were among them. They confided to us that, after reading that ad, they dashed to their gyne-cologists and insisted on pelvic exams, sonograms and CA 125 blood tests (just as the ad advises).

None, thankfully, had anything to worry about. But their experience gave us reason for concern.

IN SEARCH OF BETTER SCREENING GUIDELINES

Should every woman who notices these vague and common symptoms be concerned about the possibility of ovarian cancer and get tested? And more important, haven't better screening guidelines been established that can detect ovarian cancer in its very early stages, before symptoms develop?

In our search for answers, we spoke with leading experts at America's best cancer centers and research institutions. Several commented that, while the public-service message delivered by Gene Wilder, widower of the late "Saturday Night Live" comedienne Gilda Radner, is technically accurate, it is horribly misleading.

"Suggesting to a woman that if she has abdominal bloating she should see her doctor right away because it could be ovarian cancer is like saying if you have a headache, it's time to see a neurosurgeon because you probably have a brain tumor," says Michael Muto, M.D., head of the Familial Ovarian Cancer Center at Brigham and Women's Hospital, Harvard Medical School, Boston.

Nearly every woman has stepped into pants that won't snap. "But the percentage of women who have these symptoms and have ovarian cancer is very, very small," notes William Hoskins, M.D., chief of gynecology services at Memorial Sloan-Kettering Cancer Center, in New York City.

Besides, treating ovarian cancer after symptoms develop is more difficult.

Detecting ovarian cancer before symptoms erupt is the best bet; at this early stage, women with ovarian cancer have an 80 to 90 percent survival rate, according to the American College of Obstetricians and Gynecologists. But, to date, there are no established screening guidelines for ovarian cancer, as there are for, say, breast cancer or cervical cancer.

Organizations like the American Cancer Society and the National Cancer Institute (NCI) argue that, because ovarian cancer is rare, mass screening of all women is not economical. The average woman has a 1 in 65 chance of developing ovarian cancer over her lifetime as compared with a 1 in 8 probability of getting breast cancer.

An even more compelling argument against mass screening is that the best available tests are unreliable. The CA-125 blood test, in particular, is notoriously inaccurate. Since the only way to confirm cancer is through a surgical biopsy, mistakenly abnormal results on a CA-125 blood test too often lead to unnecessary surgery.

WHAT'S A WOMAN TO DO?

Obviously, this is another area of women's health where medical research is sorely lacking. The question is: What's the best you can do to protect yourself now?

First, nearly every expert we consulted said to keep your concern in perspective. The fact is, ovarian cancer is a relatively uncommon disease. "There will be approximately 182,000 new cases of breast cancer diagnosed this year and 22,000 new cases of ovarian cancer," Dr. Muto explains.

"This is not a disease we should be in a panic about," agrees Susan Harlap, M.D., epidemiologist at Memorial Sloan-Kettering Cancer Center. "The vast majority of women are not at risk and needn't worry."

Of course, some of us may be at higher risk. And it's important for us to know that so we can channel our concern into positive action.

FOR WOMEN AT HIGH RISK . . .

Overwhelmingly, our experts agree that the number-one risk factor for ovarian cancer is a family history of the disease. Primarily, a woman who has at least one documented case of ovarian cancer in an immediate relative--a mother, sister or daughter--is considered at high risk. Having an aunt or grandmother ups her risk, too, but not to the same degree.

It's important to note, however, that having a family history of ovarian cancer doesn't mean you're born with a time bomb ticking inside. It means that there's a chance you may have inherited a flawed gene that could make you more vulnerable to the disease. Unfortunately, there's no way to tell whether you've inherited the gene. Not yet, anyway, though Dr. Muto anticipates that within the next five years genetic testing will make it possible to do just that.

In the meantime, if you know or suspect that anyone in your family had ovarian cancer, make an appointment with a women's cancer specialist (a gynecologic oncologist) for a risk assessment.

Cancer specialists say many women mistakenly believe their families carry hereditary ovarian cancer. "It sometimes turns out that the relative had another type of cancer that spread to the ovaries. Once you put the pieces together, it really isn't ovarian cancer," says Neil Rosenshein, M.D., director of the division of gynecologic oncology at Johns Hopkins University Medical Center, Baltimore.

Another consideration is that few cases of ovarian cancer are hereditary--only 5 percent, says Dr. Rosenshein. Having an immediate relative with ovarian cancer doesn't mean it's genetic or hereditary. It could be just chance. Short of obtaining permission to see your relative's medical records (which is definitely worth the effort if you're in doubt), the only clue that you may be dealing with a hereditary disease is the age at which your relative was stricken. Familial ovarian cancer tends to strike women 10 years sooner, on average, than nonfamilial ovarian cancer. Also, a family tree strewn with multiple cases of ovarian cancer suggests a familial pattern.

Experts agree, the highest hereditary risk is reserved primarily for women who have either two or more immediate relatives (mother, sister or daughter) with documented ovarian cancer or one immediate relative and multiple distant relatives (aunt, grandmother or other) with the disease.

Apparently, too, a woman has an elevated risk of developing ovarian cancer if (1) her family tree is laden with ovarian cancer plus breast cancer or (2) her family tree has a preponderance of colon cancer along with any of these: ovarian, endometrial (uterine), lung, pancreatic or prostate cancer.

But, some experts agree, just one immediate relative is enough to nudge you into the high-risk category. Often, however, it can be difficult to prove if what a relative had was really ovarian cancer. In our opinion, unless you can prove beyond reasonable doubt that it wasn't, you'd be wise to take a cautious approach.

Being cautious means continuing to see a qualified gynecologist--preferably a gynecologic oncologist--for periodic checkups. As a woman's cancer specialist, a gynecologic oncologist has specialized training and experience to help you decide on a personal action plan. (See "How Do You Find a Qualified Doctor?" on page 64.)

According to the cancer specialists we interviewed, the best advice for women at high risk would be to have a pelvic exam and/or a transvaginal ultrasound every six months beginning between ages 21 to 25. (See "The Best Tests . . . At Least for Now.")

Dr. Rosenshein, at Johns Hopkins, usually alternates these two tests at six-month intervals for his high-risk patients. Conley Lacey, M.D., head of gynecologic oncology at the Scripps Clinic and Research Foundation, tailors the tests to each individual. He gives his high-risk patients a pelvic exam every six months and makes liberal use of transvaginal ultrasound, particularly in women who are difficult to examine because of anxiety or excess body weight or when the pelvic-exam findings are suspicious.

FOR WOMEN AT ABOVE-AVERAGE RISK . . .

Although heredity represents the most significant risk factor for ovarian cancer, 95 percent of the women who develop the disease do not have a family history of it.

The search for reasons has led researchers to identify other possible risk factors. Two groups of women have emerged with above-average risk: women who have not had children and have not taken oral contraceptives, and women who have had breast cancer.

How many ovulations you have during your reproductive years appears to be a critical issue in determining ovarian-cancer risk, explains Dr. Rosenshein. If you ovulate continually until menopause, without interruption by pregnancy, breast-feeding or the use of oral contraceptives, your ovaries are subject to monthly hormonal stimulation. This, experts believe, may increase cancer risk to the ovaries.

A woman who has had breast cancer is considered to be at increased risk for ovarian cancer as well, for reasons that are not exactly known.

Like breast cancer, ovarian cancer is an age-specific disease, meaning that it's more likely to occur as you get older. The chance of developing ovarian cancer takes its biggest jump between the ages of 50 and 65, from about 28 cases per 100,000 to 54 cases per 100,000, and peaks around age 70 to 74 with 60 cases per 100,000 women. A woman at above-average risk (because of either uninterrupted ovulation or previous breast cancer) needs to be aware that advancing age may compound her risk.

If you fit the risk profile described here, take your concerns to a gynecologist (preferably a gynecologic oncologist) and discuss an action plan that's right for you. In addition to an annual pelvic exam, some of our experts offer their patients transvaginal ultrasound and suggest that it may be wise to have one once a year, beginning at age 35, as a precaution. However, they are quick to add that, while transvaginal ultrasound is a valuable tool, it is not perfect. It can detect enlargements of the ovaries, but it cannot tell if they're due to cancer or not. So in coming up with a plan that's right for you, it's a good idea to discuss with a gynecologic oncologist the pros and cons of transvaginal ultrasound.

FOR WOMEN AT NOINCREASED RISK . . .

Each of our experts emphasizes the importance of regular gynecologic care for women who are at no increased risk for ovarian cancer, since neither CA-125 nor transvaginal ultrasound is an appropriate test for the general population.

A careful pelvic examination at the time of a Pap test (to detect cervical cancer) should be performed by a qualified physician or health professional once a year beginning at age 18 (or sooner if a woman is sexually active).

"I urge women to have a pelvic exam and Pap test every year without fail, never to miss a mammogram, and to examine their breasts every month," advises Dr. Muto.

SOURCES: Paul Blumenthal, M.D., M.P.H., director of contraceptive research and programs, department of obstetrics and gynecology, Francis Scott Key Medical Center, and assistant professor of obstetrics and gynecology, Johns Hopkins University Medical Center, Baltimore; Daniel Cramer, M.D., Sc.D., associate professor of obstetrics and gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston; Susan Harlap, M.D., epidemiologist, Memorial Sloan-Kettering Cancer Center, New York City; William Hoskins, M.D., chief of gynecology services, Memorial Sloan-Kettering Cancer Center, New York City; Conley Lacey, M.D., head of gynecologic oncology, Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla; Michael Muto, M.D., head of the Familial Ovarian Cancer Center, Brigham and Women's Hospital, Harvard Medical School, Boston; Neil Rosenshein, M.D., director of gynecologic oncology, Johns Hopkins University Medical Center, Baltimore; Theodore Speroff, Ph.D., epidemiologist, department of epidemiology-biostatistics, Case Western Reserve University, National Health Medical Center, Cleveland; Wei Zheng, M.D., Ph.D., assistant professor of epidemiology, University of Minnesota, Minneapolis.

PHOTO: A woman holding an egg

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By Toni donina , Toby Hanlon and Emrika Padus

HOW DO YOU FIND A QUALIFIED DOCTOR?
If you know or suspect that you are at risk for ovarian cancer, it's important to seek consultation with a physician who specializes in the prevention, detection and treatment of women's cancers. To locate this specialist, called a gynecologic oncologist, send a self-addressed envelope (6"x 9" or larger) with $1.25 in postage to the Society of Gynecologic Oncologists, 401 N. Michigan Ave., Chicago, IL 60611, and ask for referral information. They'll send you their membership directory, which provides names, addresses and telephone numbers of board-certified or -eligible gynecologic oncologists in your area.

THE BEST TESTS . . . AT LEAST FOR NOW
Screening for ovarian cancer is a terribly imperfect science. That's why the National Cancer Institute is planning clinical trials to help evaluate the lifesaving value of the following tests. Till the results are in, here's what we know:

Pelvic exam: a basic and essential tool in screening all women for ovarian cancer In this exam, a physician inserts one finger into the vagina and presses on the abdomen with the other hand to palpate the ovaries and feel for abnormalities. Another variation is to perform a pelvic exam, as described above, with one finger in the vagina and another in the rectum. According to Conley Lacey, M.D., at Scripps Clinic and Research Foundation, this allows for a more thorough assessment of the ovaries. Effectiveness depends, to a very large degree, on the experience and training of the physician and on the woman's build (excess abdominal weight can interfere with accuracy).

Transvaginal ultrasound: useful, in combination with the pelvic exam, to screen women at high and above-average risk. Also used to assess women whose pelvic exams are inadequate or suspicious In transvaginal ultrasound (also called sonogram), a probe is inserted into the vagina and high-frequency sound waves are bounced off the uterus and ovaries; the resulting image is transmitted to a monitor for viewing. The test can detect an enlarged ovary, which may suggest cancer. But it's far from foolproof. As William Hoskins, M.D., at Memorial Sloan-Kettering Cancer Center explains, not every enlarged ovary is cancerous. Unfortunately, determining whether it is requires a surgical biopsy. Because of that--and the high cost of the exam (about $300)--transvaginal ultrasound is reserved as a tool for women at risk for ovarian cancer.

CA-125 blood test: too troublesome to use for screening This blood test, which screens for antibodies produced by cancer cells, is notoriously inaccurate. It misses about half of the early ovarian cancers it should detect, says Dr. Hoskins. And according to an NCI study, it sometimes suggests cancer in women who are disease-free; pregnancy, endometriosis, pelvic inflammatory disease, uterine fibroids, even menstruation can skew the test results. Besides, Brigham and Women's Michael Muto, M.D., points out, CA-125 has never been approved by the FDA for use as a screening test; its only approved usage is for assessing recurrences in women treated for ovarian cancer.

SHOULD YOU TAKE BIRTH-CONTROL PILLS?
Birth-control pills interrupt ovulation, just as pregnancy does, which appears to be a plus in preventing ovarian cancer. Even using the Pill for as little as one year can reduce your risk. After four years of use, risk is reduced by almost 50 percent. That's roughly the same degree of protection as having three full-term pregnancies, says Neil Rosenshein, M.D., at Johns Hopkins.

Is that reason enough to suggest taking oral contraceptives as a preventive?

"That depends," was the consensus of our cancer experts.

For some women, it's definitely not an option. The health risks for certain women (such as those with known heart disease, high blood pressure, active liver disease or a personal history of breast cancer, stroke or phlebitis) outweigh the health benefits, according to PaulBlumenthal, M.D., M.P.H., directorof contraceptive research programs,Francis Scott Key Medical Center, Bal-timore. Likewise, the Pill is not ad-vised for women who smoke, especially if they're over 35.

But for those who can safely take the Pill and are at high risk for ovarian cancer, "oral contraceptives are certainly a strategy to consider," says Dr. Rosenshein. "I personally have prescribed them for young women with a strong family history of ovarian cancer."

William Hoskins, M.D., at Memorial Sloan-Kettering Cancer Center, agrees. "The use of oral contraceptives for two years or more does appear to significantly decrease the risk of ovarian cancer as well as endometrial cancer--and the benefits are lifelong. I think it's reasonable to recommend them for primary prevention in high-risk women."

Whether child-free or infertile women (who are considered at above-average risk) should take the Pill for prevention is hotly debated, however. "Right now, I'd be a little reluctant to recommend birth-control pills for someone who doesn't need them for contraception just because that person is in the moderate-risk category," says Dr. Hoskins. But he feels women should be given the facts about oral contraceptives' protective effect. Conley Lacey, M.D., at Scripps Clinic and Research Foundation, agrees. "I think it is something this woman needs to consider in her overall health care. You need to tell her that she may be able to reduce her risk of ovarian cancer by as much as 50 percent. Then she can make a decision about using this as a preventive measure."

It's also unclear whether women over 40 who are at high or above-average risk can benefit from the protection of birth-control pills. Despite this, several experts admitted that it's reasonable to recommend the Pill to women up to age 45 who are at risk.

For women at no increased risk, a decision to take oral contraceptives should be made strictly because of a need for contraception and not to prevent ovarian cancer, agree our experts.

TO REMOVE OR NOT TO REMOVE THE OVARIES?
That's a big question. And one that 295,000 American women say yes to each year. According to the National Center for Health Statistics, that's how many women surrender their healthy ovaries while having a hysterectomy--presumably to prevent ovarian cancer.

How many of those oophorectomies (ovary removals) are warranted?

Considering that ovarian cancer is rare and strikes just 22,000 women each year, it's fair to say that many healthy ovaries are removed unnecessarily. For most women, however, the fear of ovarian cancer overshadows the real risk-versus-benefit considerations.

"The trade-off is heart disease and osteoporosis," says Theodore Speroff, Ph.D. At Case Western Reserve University, Dr. Speroff conducted a careful risk-versus-benefit study of whether to remove or not to remove the ovaries in women in their 30s and 40s. Compared with women who kept their ovaries, these women will suffer more heart attacks and hip fractures due to osteoporosis. Hormone-replacement therapy can help protect against these serious problems, but compliance tends to be insufficient to offset the time spent without functioning ovaries. A woman who has her ovaries removed before menopause has to be willing to take hormones for the rest of her life. Also, some experts feel that estrogen provided by a pill or patch is not as good as what the body produces. "The ovaries provide a wonderful and continuous source of estrogen that I don't think can be easily replaced by estrogen therapy," says Neil Rosenshein, M.D., director of the division of gynecologic oncology at Johns Hopkins University.

Most physicians agree, it's best to hang on to healthy, functioning ovaries if you can. None of our cancer experts said they'd remove the healthy ovaries of a woman under age 40 unless she had a very strong family history of ovarian cancer (at least two immediate relatives) and had finished having children. According to Dr. Rosenshein, "as long as there is no good indication for removing them, I favor ovary preservation."

What if a woman is having a hysterectomy (surgical removal of the uterus) for other reasons? Should she consider having her ovaries removed at the same time? "After age 50, the ovaries have usually stopped functioning, so I recommend removing them," says William Hoskins, M.D., chief of gynecologic oncology at Memorial Sloan-Kettering Cancer Center. "Between ages 40 and 50, it's entirely up to the patient. However, she needs to understand the pros and cons of removing them or leaving them in. The only reason to remove them is to prevent ovarian cancer, and most women are at very low risk for the disease. Personally I prefer not to take out the ovaries in anyone under the age of 45, except when there's a family history of ovarian cancer."

A MATTER OF RISK
RISK RAISER:
Using talcum powder Several studies have linked frequent use of talc around the genital area with an increased risk of ovarian cancer. A recent study conducted by Daniel Cramer, M.D., Sc.D., associate professor of obstetrics and gynecology at Brigham and Women's Hospital and Harvard Medical School in Boston, and his colleagues found that women who used talc for genital hygiene on a daily basis for many years, particularly during their childbearing years, have an up to threefold increased risk for ovarian cancer. While cause and effect has not been established, Dr. Cramer suspects that contamination of the vaginal area with talc may allow particles to reach the ovaries through the uterus and fallopian tubes, which may cause inflammation within the ovaries, contributing to the eventual development of ovarian cancer. While the study concluded that only a small percentage of ovarian cancers arise in this manner, a regular habit of applying talc directly to the genital area or us-ing it as a dusting powder for underwear, sanitary napkins or diaphragms was discouraged by the study's authors. Although not enough women had used cornstarch powder to comment on its safety, it generally produces less inflammation and is likely to be safer for occasional use.

RISK REDUCERS:

Having children We know that a woman who has had one full-term pregnancy has a 40 percent lower risk of ovarian cancer than the woman who has had no pregnancies. With each additional child, a woman's risk drops even further, by 14 percent.

Breast-feeding In addition to all of the goodies a baby gets by being breast-fed, Mom benefits, too. Each month of breast-feeding a baby reduces her risk of ovarian cancer. Breast-feeding for a total of 12 to 24 months can reduce risk by about one-third.

Eating foods high in beta-carotene Recently, researchers at Ohio State University noted a link between a high intake of beta-carotene-rich foods, such as carrots, sweet potatoes and dark, leafy greens, and a reduced risk of ovarian cancer. Although this was a small study--213 women--its findings were consistent with several larger studies. Eating three medium carrots every five days was associated with a lower risk of ovarian cancer.

Taking oral contraceptives See "Should You Take Birth-Control Pills?" on page 66 of this issue.

Exercising Mounting studies suggest that regular exercise may help prevent colon and breast cancer. Now a collaborative study between the National Cancer Institute and the Shanghai Cancer Institute in China provides some evidence that women who held jobs requiring high physical activity may have a reduced incidence of ovarian cancer. Women who sat for long periods of time on the job or expended little energy at work had an increased incidence of the disease. While the researchers acknowledge that the jury is still out, a physically active lifestyle has so many other benefits that regular exercise seems prudent.

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