Prophylactic bilateral oophorectomy is an effective way to prevent ovarian cancers in women who are at increased risk for the disease.
Prophylactic bilateral oophorectomy is an effective way to prevent ovarian cancers in women who are at increased risk for the disease. One risk factor of importance is the presence of BRCA1 and BRCA 2 gene mutations.
“Women with a BRCA1 mutation in particular have an increased risk of ovarian cancer,” says Kathleen Malone, PhD, an epidemiologist at the Fred Hutchinson Cancer Center in Seattle.
Lifetime risk for ovarian cancer is estimated at 54% for BRCA1 mutation carriers and 23% among those with the BRCA2 mutation. This contrasts with a woman’s lifetime risk of developing ovarian cancer of 1.39 % in the general population.
The nature of the disease is another concern when trying to assess preventive treatment options. Unlike breast cancer—where there are well-regarded methods of finding and treating malignancies early in the disease process—ovarian cancer is much harder to find; it will often go undetected until it becomes symptomatic.
“We know from population data that by the time ovarian cancer is detected in most women, it is in an advanced stage,” says Malone. “One study of prophylactic oophorectomy that appeared in the New England Journal of Medicine found that 6 of 98 mutation-carrying women who underwent prophylactic bilateral oophorectomy already had developed ovarian cancers and yet had no clue until the preventative intervention found cancerous material post-operatively.”
The impact of oophorectomy on the likelihood of getting ovarian cancers in BRCA carriers is impressive.
“The benefit of a prophylactic oophorectomy is that the incidence of ovarian cancer or primary peritoneal cancer in those without ovaries is reduced to levels similar to that seen in the general population,” says Julian Schink, MD, director of gynecological oncology at the Robert H. Lurie Comprehensive Cancer Center in Chicago. “I usually tell patients that by having the operation, you won’t completely eliminate risk, but you will lower it to about the same as those without the mutation.”
An additional plus is that the risk of breast cancer in those mutation carriers who have undergone an oophorectomy is substantially lowered, possibly by as much as half. Conversely, prophylactic mastectomies have no impact on the risk for ovarian cancer.
“This is a profound secondary benefit because many women with BRCA mutations are more likely to accept treatment with a prophylactic oophorectomy,” notes Schink. “They seem to struggle more with the idea of a prophylactic mastectomy.”
The indications for suggesting the surgery are pretty straightforward as far as Dr. Schink is concerned. Anyone who is a test-proven carrier of either the BRCA1 or BRCA2 mutation should be considered unless they have been previously diagnosed with metastatic breast cancer.
He usually suggests a patient consider a prophylactic oophorectomy as soon as childbearing is completed. He prefers to do the operation by age 40, noting that the risk of ovarian cancer begins to accelerate fairly rapidly after that.
“That doesn’t mean that a woman should wait through their 30s if they have completed childbearing,” he stressed. “In my opinion it is prudent to proceed with an oophorectomy even in early to mid 30s. While it is rare, there are far too many women who develop ovarian cancer in their 30s, and many of these are mutation carriers.”
Schink suggests that everyone with a strong family history be tested for the mutation. However, some will not want to be tested, but they’ll still want a prophylactic oophorectomy. That is a very thorny ethical issue.
“I struggle with the concept of people willing to have surgery but not wanting to be tested,” he says. “Without the test all you can tell is the likelihood that one has a mutation. I generally use a cut-off of 10% likelihood of having a mutation based on personal and family histories for considering a prophylactic oophorectomy.”
Many of these people will have concerns about potential genetic discrimination. Others do not want to be labeled as “carriers.” Currently, the clinical state of the art does not support widespread use of either mutation screening or surgery for those without a strong history of breast cancers.
BRCA1/BRCA2 mutations are very rare in the general population overall. Most studies of mutation frequency have been done in clinic-based populations of women from rare, highly selected families with multiple affected members.
“Population-based studies have shown us that the majority of women with a positive family history, particularly women with a relatively sparse family history of breast cancer involving only one affected relative who was diagnosed later in life, do not carry mutations,” says Malone. “Women with multiple relatives with breast cancer, relatives with early onset disease, or a family history of ovarian cancer may have an increased chance of carrying a mutation. Women should discuss their family history profile with their care providers to determine if genetic counseling and mutation testing is warranted.”
“Prophylactic oophorectomy is recognized as the most effective way to prevent ovarian cancer in women who are at increased risk,” says Schink. “Certainly any woman with BRCA1 or BRCA2 mutation is at increased risk and deserves a discussion about the potentially beneficial uses effects of the intervention.”
Kurt Ullman is a freelance health and medical based out of Indianapolis.