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A silent killer: Its symptoms are vague and common and there's no screening test, making ovarian cancer tricky to diagnose and harder to survive
By Susan Brink
Los Angeles Times
LOS ANGELES — Like any grandparent helping a daughter with a new baby and two active toddlers, Barbara Shellow was busy: changing diapers, giving baths, reading stories and playing games. The routine had her huffing and puffing, out of sorts, tired, losing weight.
But the Los Angeles grandmother didn’t give much thought to those symptoms 11 years ago. It was Idaho, in winter. “I blamed it on the altitude, the weather, and running around after three little kids,” she says.
Like the majority of women who are eventually diagnosed with ovarian cancer, Shellow’s symptoms — fatigue, bloating, stomach upset, changes in bowel habits, loss of appetite — were as vague as they are common. She chalked them up to life and, like so many women with the disease, waited too long to go to the doctor.
The very banality of this cancer’s early symptoms is what makes it so deadly — that and the fact that there is no early-screening tool, such as a mammogram for breast cancer or a Pap smear test for cervical cancer, to either reassure women that they’re healthy or find cells at early and highly curable stages.
“Ovarian cancer is our albatross in ob-gyn oncology,” says Dr. Beth Karlan, director of the Women’s Cancer Research Institute at Cedars-Sinai Medical Center in Los Angeles. But with care, some patients will see more years than they dreamed possible when they first heard the dreaded diagnosis.
“Ten additional years is nothing to sneeze at,” Karlan says. “And the beauty of it is seeing how some of these women live each and every day of those added years.”
But compared with breast cancer, the risk of dying of ovarian cancer hasn’t improved much in the past 30 years. From the late 1970s to today, the five-year survival rate for breast cancer rose from 75 percent to 89 percent. In that time, five-year survival rates for ovarian cancer went from 38 percent to 46 percent today.
In the past decade, the ovarian cancer mortality rate has stayed the same, even as breast cancer mortality has dropped by about 2 percent a year.
The elusive goal for ovarian cancer is a simple test, like the Pap test for cervical cancer, that would find the disease early enough for it to be cured. Cervical cancer has known precursors: abnormal cells that show up years before cancer develops. And the annual Pap can find them. It’s not perfect, but if a woman has a Pap every year, even if the precursors are missed one year they’ll almost certainly show up the next — long before the eight to 10 years it takes for the cells to develop into cervical cancer.
If ovarian cancer has similar precursors, they are hidden in the ovaries, and medicine hasn’t learned how to get at them for routine screening. So women and their doctors remain unaware of the disease as it develops into Stage 1 cancer and beyond.
“In the first stage, ovarian cancer can be cured 95 percent of the time,” says Dr. Robert Morgan, oncologist and researcher at the City of Hope National Medical Center. But fewer than 20 percent of women find it that early.
So far, the only test for ovarian cancer is the CA125 test, a blood test that measures a protein found in greater concentration in ovarian cancer cells than in other cells. But as a screening tool, the test is not specific enough. About 20 percent of women with ovarian cancer don’t have an elevated CA125 count at the time of diagnosis. And of those who do have a high count, only about 3 percent have ovarian cancer.
Combined with an ultrasound examination of the ovaries, the test can be useful for women at high risk for ovarian cancer: those with a family history of the disease; who carry the BRCA1 or BRCA2 gene; or who have had breast cancer. But even then, the test provides only short-term reassurance. And so use of the CA125 test is limited largely to monitoring women who know they have ovarian cancer to see how well chemotherapy is controlling the spread of the disease.
There have been disappointments in the search for a better test. A few years ago, a test called OvaCheck offered great promise, only to fall flat as experts questioned its ability to test women outside a laboratory setting.
The same hope and fear is percolating over a new test, OvaSure, which measures CA125 and five other proteins in the blood that are produced by a tumor or in reaction to one.
In a February study in the journal Clinical Cancer Research, the test correctly classified samples in 221 of 224 women, some of whom had ovarian cancer and others who did not. But experts say that the cancers identified were from women who already were diagnosed with ovarian cancer, and thus the test has yet to be proven as an early screening tool.
OvaSure has been available for use in doctors’ offices since June without approval from the Food and Drug Administration. The test did not need such approval because of an FDA rule exempting tests handled at a single laboratory. All OvaSure samples are sent to LabCorp, the clinical laboratory company based in Burlington, N.C., that offers the test.
But in July, the Society of Gynecologic Oncologists issued a statement saying that the test needs additional research. And in September, the FDA wrote to LabCorp expressing the same concern and telling the company it does, indeed, need FDA permission before OvaSure can be marketed. The agency and the company remain in discussions.
Roughly 20 percent to 30 percent of late-stage ovarian cancer patients will survive longer than five years. “During that time you need a specialist who can help you see the optimal next steps, someone guiding you,” Karlan says.
More than a decade after her diagnosis, Shellow is one of the lucky ones. At the onset, she had surgery — an hours-long procedure, in which a surgeon examines the peritoneal cavity, searching for every sign of escaped, floating tumors and plucking them out. The more thorough the surgeon is at removing tumors, the better the odds that a woman will survive longer.
After Shellow’s surgery and chemotherapy came the relief of remission and then, five times, the heartbreak of recurrence. Each time, she’s tried something new: another round of chemotherapy, a clinical trial, an experimental protocol. “They all did the trick, put me in remission for 12 to 15 months or more,” she says.
Her bad luck in inheriting the BRCA2 gene meant that she had a much greater risk of ovarian cancer in the first place. (The gene also raises the risk of breast cancer; Shellow is a breast cancer survivor.) But that gene mutation turned in her favor for treatment, because science has learned a lot about the BRCA mutations.
“Her tumor’s molecular signature is sensitive to certain chemotherapy drugs, in particular the platinum agents. So we were able to choose combinations of chemotherapy that took advantage of that,” Karlan says. “It played a role in her long survival, in our ability to personalize her treatment prescription.”
Today Shellow is taking eight pills a day, drugs known as PARP inhibitors that may specifically target BRCA-related cancers. “You try to soldier on through all these things with a good attitude,” she says.
She’ll turn 70 in January.
Common, frequent early symptoms
LOS ANGELES — Laurie Gray’s mother died of ovarian cancer at age 41, more than 30 years ago. For Gray, a Los Angeles attorney, a cloud of concern lingered over her own health. She’s 52 now, and a few years ago, she tested positive for the BRCA1 gene. Shortly afterward, she had her breasts and ovaries removed as a precaution.
For women with the gene, the risk of ovarian cancer spikes from a 1 in 70 chance to as high as a 6 in 10 chance. “Their risk goes up hugely,” says Dr. Carmel J. Cohen, co-chairman of the Ovarian Cancer Research Fund. “Those women ought to have their ovaries removed.”
But most women don’t have the BRCA1 or BRCA2 genes known to increase risk, and ovarian cancer can still swoop in out of the blue. Fortunately, researchers are looking more closely at the vague symptoms commonly felt by women who later were diagnosed with ovarian cancer. And they have found some subtle differences that may help women know when they should press doctors for a closer medical look.
In a 2004 report in the Journal of the American Medical Association, responses by women with ovarian cancer were compared with those from women without cancer who visited primary care clinics. Oddly, gynecological symptoms, such as menstrual irregularities, were less likely to be reported by women with ovarian cancer.
Instead, the most frequent early symptoms connected to ovarian cancer were: back pain, fatigue, indigestion, urinary problems, constipation, abdominal pain, bloating and increased abdominal size. And some 43 percent of the women had three of these symptoms — bloating, increased abdominal size and urinary tract problems — simultaneously.
The women with ovarian cancer complained of having several symptoms every day, compared with the control group of women, who complained of one or two symptoms several times a month.
When women who have not experienced these early symptoms are suddenly being troubled by combinations of two or three of them, several times a month, it adds up to the best early warning signal available so far, says Dr. Robert Morgan, oncologist and researcher at the City of Hope National Medical Center in Duarte, north of downtown Los Angeles.
“It used to be felt that women with early-stage disease did not have symptoms. Now, it’s looking like up to 90 percent of women have early symptoms,” Morgan says.
Adds Cohen, “It’s very important that women be told that when they go to their provider with these symptoms, they must tell the provider, ‘Prove to me that I don’t have ovarian cancer.’ ”
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