Ovarian cancer — What can be done to prevent spread of the disease?
Prevention approaches eyed for women with and without BRCA mutations
EXECUTIVE SUMMARY
Women with breast cancer susceptibility gene (BRCA) mutations are at risk for breast and ovarian cancers. Ovarian cancer often escapes early detection because laboratory and imaging screening tools are less effective than those developed for breast cancer. Ovarian cancer is marked with a less-robust five-year survival rate (44%), compared with nearly 90% for breast cancer.
• About 12% of women in the general population will develop breast cancer, compared with about 60% of women who have inherited a harmful BRCA1 or BRCA2 mutation.
• About 1.4% of women will be diagnosed with ovarian cancer, but 15-40% women with a BRCA1 or BRCA2 mutation will develop the disease.
Much media attention has been given lately to actress Angelina Jolie, who underwent prophylactic double mastectomies after learning that she had a breast cancer susceptibility gene 1 (BRCA1) abnormality. But women with harmful BRCA mutations also are at risk for ovarian cancer, which often escapes early detection because laboratory and imaging screening tools are less effective than those developed for breast cancer.1 Subsequently, ovarian cancer is marked with a less-robust five-year survival rate (44%), compared with nearly 90% for breast cancer.2
BRCA1 and BRCA2 belong to a class of genes known as tumor suppressors. In normal cells, BRCA1 and BRCA2 help ensure the stability of the cell’s genetic material and stem uncontrolled cell growth. When mutation occurs, however, both have been linked to the development of hereditary breast and ovarian cancer.
According to the National Cancer Institute, the likelihood that a breast and/or ovarian cancer is associated with a harmful mutation in BRCA1 or BRCA2 is highest in families with a history of multiple cases of breast cancer, cases of breast and ovarian cancer, one or more family members with two primary cancers, or those with an Ashkenazi (Central and Eastern European) Jewish background. However, not every woman in such families carries a BRCA mutation, and not every cancer in such families is linked to a BRCA mutation. Also, not every woman with a harmful BRCA1 or BRCA2 mutation will develop breast and/or ovarian cancer.3
About 12% of women in the general population will develop breast cancer during their lives, compared with about 60% of women who have inherited a harmful BRCA1 or BRCA2 mutation. In comparison, about 1.4% of women in the general population will be diagnosed with ovarian cancer, but 15-40% women with a BRCA1 or BRCA2 mutation will develop the disease.3
Genetic tests, performed on blood samples, can detect harmful BRCA mutations. According to the National Cancer Institute, there are no current standard criteria for recommending or referring someone for BRCA1 or BRCA2 mutation testing.3 Genetic counseling generally is recommended before and after tests to help patients understand their risk assessment.
In a family with a history of breast and/or ovarian cancer, the National Cancer Institute indicates that it might be best to first test a family member who has breast or ovarian cancer. If that person is found to have a harmful BRCA1 or BRCA2 mutation, then other family members can be tested to see if they also have the mutation. Cost for such tests can range from several hundred to several thousand dollars; patients may wish to consult their insurance companies for the extent of coverage for such tests.3
Fallopian tube targeted
Like Jolie, many women with harmful BRCA mutations are considering removal of breasts, ovaries, or fallopian tubes to lower their cancer risk. Women who elect such surgery see themselves as "previvors — getting ahead of possible impact from cancer spread.4
High grade serous ovarian cancer, which causes 70% of ovarian cancer deaths, can originate in the fallopian tubes.2 For women with harmful BRCA mutations, current medical practice looks to bilateral salpingo-oophorectomy at age 40 or upon completing childbearing. Bilateral salpingo-oophorectomy reduces the risk for ovarian and fallopian tube cancers by 85%-90%.2 However, removal of ovaries leads to premature menopause, which can have adverse effects.5
Because most BRCA-associated ovarian cancers appear to arise in the fallopian tube, salpingectomy might be an alternative to bilateral salpingo-oophorectomy. Researchers recently compared the costs and benefits of salpingectomy with bilateral salpingo-oophorectomy among BRCA mutation carriers. They found that when considering quality-adjusted life expectancy, bilateral salpingectomy with delayed oophorectomy is a cost-effective strategy and might be an acceptable alternative for those unwilling to undergo bilateral salpingo-oophorectomy.5
There is an ongoing study in France that is evaluating risk-reducing fimbriectomy (removal of the distal part of the fallopian tube), as opposed to salpingectomy, as an alternative to standard bilateral salpingo-oophorectomy, says Janice Kwon, MD MPH FRCSC, assistant professor in the Division of Gynecologic Oncology at the University of British Columbia in Vancouver.
Results from that study will not be available until several years from now, she states.
Kwon’s research team, which published the cost/benefit study, is performing an analysis to evaluate whether salpingectomy, with or without oophorectomy, would be a cost-effective risk-reducing intervention for women in the general population or for women who have a higher-than-average risk, but do not carry a mutation in BRCA1 or 2.
When to remove tubes?
Patients and providers are showing a growing acceptance of routinely removing the fallopian tubes, but preserving the ovaries during hysterectomy to avoid risk of ovarian cancer. Women who do not have harmful BRCA mutations are considering such a move, as indicated in a recent paper presented at the American College of Obstetricians and Gynecologists’ annual meeting.6
Researchers at the University of California, Los Angeles (UCLA) undertook a retrospective study of women who underwent an abdominal, vaginal, or laparoscopic hysterectomy with ovarian preservation at Olive View-UCLA Medical Center between January 2009 and June 2012. Investigators reviewed medical records for 1,060 patients and collected data on these women about being offered bilateral salpingectomy, as well as actual completion of the procedure at the time of hysterectomy. All but two patients who were offered salpingectomy in the study consented. Six of the consenting patients could not have the procedure due to complications. Bilateral salpingectomy rates rose from 3% in 2009 and 2010 to 33% in 2011 and 77% in the first six months of 2012, data indicate.6
"There is high patient and provider acceptance of this practice, says Susan Park, MD, UCLA researcher. "Our study aids physicians in assuring patients that there does not appear to be any increased risk of surgical complications associated with performing salpingectomy at time of hysterectomy.
The UCLA study did not look at the possible role or risks and benefits of salpingectomy in patients undergoing tubal sterilization procedures, or the role of salpingectomy in women with a genetic predisposition to ovarian cancer. It examined only surgical morbidity.
"We did not study the important long-term outcomes, such as the risks of developing post-hysterectomy adnexal masses or cancers, stated Park in a press release accompanying the ACOG presentation. "Such a study is an important next step, but would need to be done at a much larger scale than a single institution study.
Despite the progress that has been made in surgical approaches to reducing ovarian cancer risk, there is still work to be done in developing tests that can provide early diagnosis of the disease, says Robert Hatcher, MD, MPH, professor emeritus of gynecology and obstetrics at Emory University School of Medicine in Atlanta.
"We do not have tests that will diagnose ovarian cancer early, says Hatcher.
REFERENCES
1. Weiss M. Ovarian cancer and its insidious threat. Wall St J, May 28, 2013: A15.
2. Kovacs P. Will removing fallopian tubes reduce risk in BRCA carriers? Accessed at http://bit.ly/14pWQrQ.
3. National Cancer Institute. BRCA1 and BRCA2: Cancer risk and genetic testing. Accessed at http://1.usa.gov/5te4S.
4. English B. Striking before cancer can. Boston Globe, May 28, 2013. Accessed at http://bo.st/14LXnks.
5. Kwon JS, Tinker A, Pansegrau G, et al. Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol 2013; 121(1):14-24.
6. Park SK, Rodriguez-Triana V, Amneus MW, et al. Incorporating routine bilateral salpingectomy at the time of hysterectomy with ovarian preservation. Presented at the 61st annual clinical meeting of the American College of Obstetricians and Gynecologists. New Orleans, May 2013.
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