Toward Earlier Detection of Ovarian Cancer The Wall Street Journal AUGUST 04, 2009

HEALTH JOURNAL
AUGUST 04, 2009
 
http://online.wsj.com/article/SB10001424052970204313604574328573230828740.html

Toward Earlier Detection of Ovarian Cancer

By MELINDA BECK


 

Two new studies offer a glimmer of light into the dark puzzle of ovarian cancer, which remains one of the most deadly cancers because it is so difficult to detect early.

Researchers in the United Kingdom have identified a new genetic variation that appears to raise a woman’s risk of developing ovarian cancer. BNC2, as the gene is called, is far more common than the previously identified genes, BRCA1 and BRCA2, and it doesn’t raise the risk of ovarian cancer nearly as much, according to the study, which was published in Nature Genetics. But it’s the first of what scientists believe will be many common gene variations linked to ovarian cancer that, when combined, may raise the risk significantly.

“This study confirms that ovarian-cancer risk is partly determined by genetic variants present in a large number of women,” said Andrew Berchuck, a gynecologic oncologist at Duke University and head of the Ovarian Cancer Association Consortium, which enables researchers world-wide to work together to speed up discoveries.

Patrick Brown

Researchers at Stanford University say most ovarian tumors are the size of an onion when diagnosed—but tests would need to detect tumors the size of a peppercorn in order to significantly cut the mortality rate.

The second study, published in the online journal PLoS last week, provides new insights into what ovarian tumors typically look like before they are discovered. Researchers at Stanford University School of Medicine and the Canary Foundation, a nonprofit group dedicated to early cancer detection, analyzed reports of tumors found in ovaries and fallopian tubes that were removed as a precaution from women who had the BRCA1 mutation. Even though all the women were believed healthy at the time, about 8% had undiagnosed serous ovarian tumors, the most deadly kind.

Using a mathematical model, the researchers determined that most such tumors remain extremely small—less than 1 centimeter in diameter—for about four years before metastasizing, and about half of them were still just 3 centimeters across by the time they did spread.

That’s both bad and good news: The researchers say tests need to be hundreds of times more sensitive than they currently are to detect such tumors, but “at least we now know what we are looking for,” says lead investigator Patrick Brown, a Stanford biochemist. “If we can develop the right test, we have a long window of opportunity.”

Finding a way to detect tumors early has been the Holy Grail of ovarian-cancer research for decades. When diagnosed and treated early, ovarian cancer has a 90% cure rate. But the vast majority of cases are detected in more-advanced stages, after spreading to lymph nodes or distant parts of the body. In such cases, only about 45% of patients survive more than five years.

As a result, even though ovarian cancer is relatively rare—the lifetime risk is 1 in 70, compared with 1 in 8 for breast cancer—it is frequently fatal. An estimated 21,000 women in the U.S. were diagnosed with ovarian cancer in 2008, and more than 15,000 died from it.

Researchers have been hoping to find a screening test that would help detect ovarian cancer early, much like prostate-specific antigen, or PSA, tests do with prostate cancer and mammograms do for breast cancer. But the best tests to date—a CA 125 blood test and a transvaginal sonogram—give many false positives as well, so neither are currently recommended for screening the population at large.

Both tests are recommended for women who have a family history of ovarian cancer, or who experience symptoms such as abdominal bloating, pain, change in bowel habits or unusual fatigue. It’s unclear how big a tumor has to be before such symptoms are evident, but even when they are, women often ignore them and doctors often dismiss them as gastrointestinal upset.

In a recent survey by the National Ovarian Cancer Coalition, a nonprofit advocacy group, 83% of women said their doctors had not discussed the symptoms of ovarian cancer with them, and 62% of Americans believe—erroneously—that a Pap smear can diagnose it.

“Nobody knows your body as well as you do. If the symptoms are there, pay attention,” says April Donahue, an ovarian-cancer survivor from Quakertown, Pa. When she was 24, she went to four different doctors for pain, fatigue and bloating before one removed what he thought was an ovarian cyst. It turned out to be cancer. Ten years later, Ms. Donahue’s symptoms returned, and doctors again brushed it off. But she insisted on having her remaining ovary removed, and cancer was discovered again. “Hey, I’m lucky. I’m an 18-year survivor, and not a lot of women can say that,” she says.

Women with numerous cases of breast, ovarian and colon cancer in their extended families are urged to see a genetic counselor, who may suggest testing for a BRCA mutation. Only about one in every 500 women carries either BRCA1 or BRCA 2, but when they do, they have five times the usual risk of breast cancer, and between three and eight times the risk of ovarian cancer.

“If I hadn’t opened that envelope, I would have passed away years ago,” says Donna Lackey, 42, of Southlake, Texas. Her mother and grandmother died of breast cancer in their 40s, and in 2002, a cousin wrote to say that she and her siblings had tested positive for BRCA1. Ms. Lackey tested positive too and scheduled what she thought would be a preventative double mastectomy and oophorectomy (removal of the ovaries). But the surgeons found that ovarian cancer had already spread throughout her abdomen and lymph nodes, even though she had no symptoms whatsoever.

Telltale Symptoms

See your doctor if you experience any of these for more than three weeks:

Abdominal bloating

Vague but persistent gastrointestinal complaints

Change in bowel habits

Frequency or urgency of urination

Unexplained weight gain or loss

Abnormal vaginal bleeding

Source: Ovarian Cancer Research Fund

Ms. Lackey has since had seven cancer recurrences and has been on chemotherapy continuously for the past year. Still, she has beaten the five-year odds and is grateful she had the surgery. “If I hadn’t, my boys would have lost their mom in second and fifth grade. Their whole lives would have been different,” she says.

To date, only about 25% of ovarian-cancer cases appear to have a family connection. The rest are probably related to unknown genetic problems or to environmental causes, or an interplay of both. “We don’t believe that anybody inherits cancer. What you may inherit is a predisposition to it,” says Thomas Sellers, a genetic epidemiologist at Moffitt Cancer Center in Tampa, Fla., who expects his group to identify several more gene variations—called SNPs, for single-nucleotide polymorphism—linked to ovarian cancer within the year.

Other doctors at Moffitt are analyzing the gene expressions in tumors themselves, rather than the DNA of patients. “The SNPs study is looking at the individual components of the engine,” says Johnathan Lancaster, head of women’s oncology at Moffitt. “We’re looking at differences in the speed the cars go.” In a pilot study, he is using those genetic fingerprints in tumors to select chemotherapy drugs for patients with recurrent ovarian cancer—a major step toward individualized cancer treatment.

Researchers also have high hopes for preventing ovarian cancer in the first place. Bearing children, breast-feeding them and taking birth-control pills for at least five years all seem to lower the risk significantly—probably because each suppresses ovulation temporarily. Maintaining a healthy weight is also recommended.

Doctors often recommend that women at high risk who have completed their families have their ovaries and fallopian tubes removed, which can cut the cancer risk dramatically. That does put them into immediate “surgical” menopause, and in rare cases, ovarian cancers can still occur in the lining of the abdominal cavity. But Carmel Cohen, a gynecological oncologist at Mount Sinai School of Medicine in New York and vice chair of the Ovarian Cancer Research Fund, says he knows of no data to suggest that taking low-dose estrogen raises the risk of cancers after ovaries have been removed.

Researchers are also looking for more specific markers that might be evident in blood, in vaginal fluid or even the breath of women with early cancers.

Experts advise women to check their family history and look out for symptoms. As Dr. Cohen says: “If a woman has symptoms that are recent, persistent and otherwise unexplained, she should go to her provider and say, ‘Prove to me I don’t have ovarian cancer.’”

Write to Melinda Beck at HealthJournal@wsj.com

Correction: In a recent survey by the National Ovarian Cancer Coalition, 83% of women said their doctors had not discussed the symptoms of ovarian cancer with them. An earlier version of this article incorrectly called the group the National Ovarian Cancer Association.

hi,

take note to study DR. BRODA BARNES book on HYPOTHYROIDISM, THE UNSUSPECTED ILLNESS and do the barnes basal temperature test. Most hormonal imbalances (breast, ovary and prostate cancers) are due to the thyroid malfunctioning. Minimize eating flours products and meat products with hormones.

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