TORONTO - Women who carry a BRCA genetic mutation have a significantly reduced chance of developing ovarian cancer and dying prematurely if they opt to have their ovaries and fallopian tubes preventively removed earlier than later, a study suggests.
The Canadian-led study, published in the Journal of Clinical Oncology, suggests women with an inherited BRCA1 mutation should consider having ovary-removal surgery by age 35. Those with BRCA2 could wait to have an oophorectomy, as it is called, until age 45, because the cancer risk with that mutation tends to kick in about 10 years later.
"Essentially, you want to go early enough that the chance of getting cancer is essentially minimized, and that occurs about age 35," principal researcher Dr. Steven Narod said of women with BRCA1, adding that removing the ovaries results in immediate menopause.
Some women hesitate to have the surgery at that age because they want to preserve their fertility so they can have children, while others want to avoid the effects of menopause, said Narod, director of the Familial Breast Cancer Research Unit at Women's College Hospital in Toronto.
"But if you wait until age 40, there is about a four per cent chance of getting ovarian cancer," he said Monday. "And if you wait until age 50, the risk of ovarian cancer between age 35 and 50 is about 14 per cent."
"That's too high a risk to take."
Having a mutation in either of the BRCA genes leads to an elevated risk of breast and some gynecological cancers. Certain ethnic groups, among them Ashkenazi Jews, have a higher prevalence of these genetic mutations.
Within the general population, the average Canadian woman has about a one per cent risk of developing ovarian cancer in her lifetime. For women with a BRCA1 mutation, the lifetime risk is a "staggeringly high" 40 per cent; for BRCA2, it's 20 per cent.
"So if we don't do the oophorectomy, we would expect 40 per cent of those (BRCA1) women to get ovarian cancer by age 75. With the operation, it was reduced to about six per cent," said Narod, noting that the surgery isn't 100 per cent protective for all women.
When Leela Goldhar-Waxman of Toronto found out almost two years ago that she carries the BRCA2 mutation, she decided to have a double-mastectomy — followed by reconstruction — to prevent breast cancer. Last September, she had her ovaries and fallopian tubes removed as well.
Hearing the statistics around the probability of developing ovarian cancer, and already having lost some friends with the genetic mutation to the disease, the decision was not a difficult one to make, said Goldhar-Waxman.
The 38-year-old has three children — a daughter, 12, and two sons, 10 and 9 — so fertility was not a concern. Hormone replacement therapy helps with the symptoms of premature menopause, and any adverse effects that develop she will deal with if and when they arrive, she said.
While opting for the surgeries has made her feel empowered, she still worries about getting other cancers that are more prevalent with BRCA2, among them bowel and pancreatic tumours.
"I know I have done the best I can do to be here for as long as I can for my children and my husband and my family," said Goldhar-Waxman.
"I was given the greatest gift," she said of the BRCA test. "I was given a golden ticket for survival."
In the study, nearly 5,800 women with a BRCA mutation were followed for almost six years by researchers at centres in Canada, the U.S. and Europe. The researchers evaluated the effect of preventive surgery in reducing death and the risk of ovarian, fallopian tube or peritoneal cancer in the women.
They found surgical removal of the ovaries was associated with an 80 per cent drop in the risk of developing those cancers; a 77 per cent lower risk of premature death from all causes, including cancer; and a 68 per cent lower risk of death from all causes in women who had previously had breast cancer.
"In this study, 154 women got cancer that would have been prevented had they had the oophorectomy ... when we had recommended it," Narod said.
In general, women with BRCA mutations also have a 60 to 70 per cent chance of developing breast cancer, and a further 34 per cent chance of cancer in the opposite breast within 15 years. Many women facing that risk opt to have a double mastectomy as a preventive measure.
But even without a mastectomy, having the ovaries removed can reduce the risk of developing breast cancer to a certain extent, said Narod, likely because it diminishes the sex hormones estrogen, progesterone and testosterone.
"I think women who have had breast cancer in the past and haven't had an oophorectomy should be considering to go back and have it done, even after breast cancer," he said, referring to women who have one of the mutated BRCA genes.
The surgery would include removal of the fallopian tubes, called a salpingectomy, as a significant number of ovarian cancers are known to originate in the tubes.
Dr. Cathy Popadiuk, an associate professor of gynecologic oncology at Memorial University in St. John's, NL, said the study authors report "very exciting and interesting findings about the role of oophorectomy in women with BRCA mutations."
"What is most exciting is not only the overall effects to prevent gynecologic cancers such as ovarian and fallopian tube (if the fallopian tubes are also removed), but the great impact on breast cancer incidence and mortality, and indeed, overall mortality," Popadiuk said by email.
"This study suggests that the benefits from oophorectomy (and salpingectomy) have greater implications to overall cancer health than most people suspected," she said. "Hopefully this work will offer more support for the value of oophorectomy in the prevention and control of breast cancer in BRCA carriers, in addition to the surgically difficult prophylactic mastectomy."
Narod said while oophorectomy is considered a safe procedure, the resulting premature menopause can carry long-term adverse effects on cardiovascular and bone health, which need to be studied further.
To deal with the effects of early menopause, such as hot flashes, women are offered hormone replacement therapy, he said.
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