Can test avert ovarian cancer, menopause?
Removal of fallopian tubes could cut risk of deadly disease, surgeons say
Anna Hargrove learned she carries a genetic mutation that predisposes women toward breast and ovarian cancer at 27, which was no surprise given her family history.
Hargrove, cautious by nature, did what a lot of women with the mutation do: She underwent a double mastectomy. She then married, delivered three children and, shortly after her 40th birthday three weeks ago, had surgery to reduce the risk of ovarian cancer.
But there was one significant difference: The procedure didn’t involve her ovaries.
Instead, MD Anderson Cancer Center surgeons removed Hargroves’ fallopian tubes, part of an experimental study investigating whether taking out only the slender ducts that carry eggs can prevent the devastating disease, at least in the short run. The idea, based on a relatively recent discovery that ovarian cancers often start in the fallopian tubes, is to delay menopause prematurely brought on by the removal of the ovaries, the recommended course of action for women at high risk.
“Who wants to go through menopause at 40?” asks Hargrove, an Austin stay-at-home mom whose mother was diagnosed with breast cancer at 37 and whose grandmother died of the disease at 67. “I was prepared to do it, but when MD Anderson gave me the option
of just removing my tubes, I jumped at it.”
‘Guinea pig’ patients?
The idea is controversial in some cancer-care circles — critics say the women are guinea pigs assuming an unknown degree of risk — but if the study is successful, it could dramatically change the way doctors and their patients approach the prospect of ovarian cancer, one of the most lethal types of the disease.
The practice eventually might benefit not just women with one of the mutations but perhaps many not at high risk. Another study being conducted in Canada is investigating the approach in women without such a mutation who don’t want to have any more children and were planning to have their tubes tied. Instead, they’re having the fallopian tubes removed and are being tracked in the coming decades to determine whether their absence decreases women’s odds of developing ovarian cancer.
A better approach certainly would be welcome. Ovarian cancer mortality rates have declined only slightly in the nearly half century since President Richard Nixon declared the War on Cancer, and the five-year survival rate ranges from 10 percent to 40 percent when the cancer has spread, depending on how much. It kills about 14,000 U.S. women annually.
There is no screening test, and because the disease produces no obvious symptoms, it typically remains undetected as it silently grows.
That’s why doctors recommend women who have a mutation in either the BRCA1 or BRCA2 genes — mutations that allow cells to develop instability that can lead to cancer — have their ovaries removed not long after childbirth is done, drastic as that may sound. Compared to the general population’s 1 percent risk of developing ovarian cancer, women with BRCA1 and BRCA2 mutations have a 39 percent and 17 percent risk, respectively. Women are advised to have their ovaries removed by 40 if they have a BRCA1 mutation and by 45 if they have the BRCA 2 mutation.
Removing the fallopian tubes and ovaries eliminates the possibility of ovarian cancer, though a less than 5 percent risk of a related cancer nearby remains, says the principal investigator of the study. And because the ovaries make estrogen, the hormone that fuels many breast cancers, their removal reduces that risk by 50 percent, too, according to the National Cancer Institute.
The problem is that the removal of the ovaries brings on menopause 10 to 15 years before its normal onset. In their late 30s or early 40s, such women suddenly start experiencing hot flashes, vaginal dryness, painful intercourse and decreased libido. They also develop a higher risk for developing heart disease and osteoporosis.
“Menopause has such a huge impact on quality of life and even feelings of being a woman,” says Dr. Karen Lu, the study’s principal investigator and MD Anderson’s chair of gynecologic oncology and reproductive medicine. “It’s a life-changing time.”
A disease-origin hint
Following surgeries on BRCA mutation carriers in the 1990s and 2000s, Lu was one of a number of pioneers who documented evidence of cancer in the fallopian tubes but not yet in the ovaries, the key impetus for the new research. Before that, statistics showing women who had their tubes tied developed ovarian cancer 50 percent less often than women who didn’t was a hint that the disease might originate in the tubes.
That discovery was not lost on the ovarian cancer advocacy community, desperate for a new strategy better balancing risks and quality of life. Lu emphasizes that they pushed for the study, which still calls for the removal of the ovaries. Removing the tubes at an earlier time just buys women at risk additional time before the plunge into menopause.
The push speaks to the change from 15 or more years ago, when Lu’s patients at risk for ovarian cancer were mostly women with breast cancer, typically already in menopause as a result of their treatment with chemotherapy.
Due to the increase in genetic testing, Lu says, her at-risk patients now arrive at a younger age, cancer-free, pre-menopausal and faced with hard decisions about how to respond.
Some decide to roll the dice and keep their ovaries. The new approach would give them another option.
A gutsy decision
Dr. Christopher Crum, a pathologist at Boston’s Brigham and Women’s Hospital and another discoverer of ovarian cancer’s roots in the fallopian tubes, isn’t so sure it’s a good idea yet to remove only the tubes as an intermediary step. He worries because researchers haven’t been able to trace some advanced malignancies back to the fallopian tubes.
“If you’re wrong, you’re looking at some women whose decision at 40 may mean they’re never going to see their grandchildren,” Crum says. “It makes me pretty nervous. I think women opting to just have their tubes removed have a lot of guts.”
Lu, who knows ovarian cancer’s ravages all too well from caring for such patients, acknowledges the trial makes her nervous, too. But she says such research is the responsible thing to do so doctors can counsel women not inclined to have their ovaries taken out whether removing their tubes is a reasonable option.
The rules call for the study to be stopped if more than two women develop ovarian cancer, something Lu doesn’t anticipate given existing data on when cancer originates in the fallopian tubes or ovaries in BRCA patients. Lu also says that the vast majority of ovarian cancer originates in the fallopian tubes in BRCA patients. Most of the ovarian cancers not traceable to the tubes occur in women without such a mutation, she says.
Lu says it will take a bigger study for the idea to be accepted, likely one with 1,000 or more patients. The current study, 18 months in and about halfway through, will enroll 270 patients at seven institutions around the nation — half will have their tubes and ovaries removed, and half will have just their tubes removed initially, advised to follow up with the ovaries by the BRCA1 and BRCA2 recommended removal dates. Patients who wait until later to have them removed or eschew such removal altogether also will provide useful information, Lu noted.
Happy with new option
Women with a genetic mutation that predisposes them to ovarian cancer represent only 20 percent of the roughly 22,000 diagnoses annually. Trials like the Canadian one being conducted on lowerrisk women who had planned on having their tubes tied could show a wider application. But results won’t be known for decades, inasmuch as ovarian cancer’s average age of diagnosis is 60. Even then, assuming the trial shows a benefit, it likely would require discussion of whether such tube removal would be a smart policy recommendation in low-risk women not planning on getting them tied.
For now, BRCA patients participating in the research express happiness to have a new option. Hargrove, who has the BRCA2 mutation and plans to have her ovaries removed at 45, says she feels good about the future because “knock on wood, family members only had breast cancer, not ovarian cancer, and this approach is still pretty conservative.”
Some patients, like Amy Starr, have already finished the two-step process. A BRCA1 carrier who who took the test hoping it would prove that she didn’t have a mutation and put her mind at rest, she had her tubes removed at 37 as part of an MD Anderson pilot study five years ago, then her ovaries at 40. Cancer, mostly breast and ovarian, has been diagnosed at least seven times in her family, beginning with her grandmother’s generation.
“I was pretty nervous about the mutation, both the cancer risk and the idea of having my ovaries out even though I felt normal, healthy,” said Starr, a Houston surgical nurse.
“Being able to just have my tubes out initially was great,” she said. “It gave me a good feeling that I’d done something to protect myself without having to sacrifice anything.”
“If you’re wrong, you’re looking at some women whose decision at 40 may mean they’re never going to see their grandchildren. It makes me pretty nervous.” Dr. Christopher Crum, pathologist at Brigham and Women’s Hospital