FORCE has a strong commitment to promoting research to benefit our community. We advocate for more research funding, educate people about available studies, and report findings back to our community.
by Sue Friedman and Helen Smith
Emerging research suggests that many ovarian cancers in BRCA gene mutation carriers may actually start in the distal fallopian tube (part of the tube closest to the ovary), causing researchers to question whether preemptively removing the tubes might reduce cancer risk. Although experts agree this important issue deserves more research, identifying the best approach is the subject of debate. At our annual conference in 2012, gynecologic oncology experts Dr. Illana Cass and Dr. Douglas Levine presented the history of hereditary ovarian cancer research and the pros and cons of further research on salpingectomy to lower the risk in high-risk women.
Since the discovery of BRCA mutations and the availability of commercial BRCA testing, experts have recommended that women with mutations remove their ovaries between the ages of 35 - 40 or after childbearing is completed. In the early years after the discovery of BRCA, little data backed up these recommendations, but common sense seemed to dictate that removing the ovaries at a young age would also remove much of the risk. Subsequent research proved that removing the ovaries and tubes lowers the risk for ovarian cancer; more recent research shows that it also lowers the risk of death from breast cancer and ovarian cancer. Some women, however, still develop primary peritoneal cancer, a gynecologic cancer that behaves like ovarian cancer but may occur even after the ovaries are removed.
As hereditary gynecologic cancer research evolved, a new hypothesis about the origin of ovarian cancers in mutation carriers emerged. Previously, all ovarian cancers were believed to develop in the lining of the ovary as a result of the constant rupture and repair process during ovulation. Researchers established early on that fallopian tube cancer — which is rare in the general population — is more common in women with BRCA mutations. This discovery led to recommendations favoring bilateral salpingo-oophorectomy (BSO) — removal of the ovaries and the fallopian tubes — to greatly lower the risk of these cancers in high-risk women. The discovery of unexpected, or “occult” fallopian tube cancers during prophylactic surgery led to recommendations of “serial sectioning” of the fallopian tubes by pathologists, a procedure involving more intensive evaluation of the fallopian tubes to find hidden cancers that might require further surgery or treatment.
Careful examination of the fallopian tubes from research studies such as GOG-0199 led to the discovery of precancerous fallopian tube changes called “serous tubal intraepithelial carcinoma “ (STIC) lesions. No similar lesions have been found in ovaries of high-risk women. This discovery is good news for the high-risk community because it is the first time that precancerous changes have been identified as part of the process of normal tubal or ovarian tissue becoming cancer. This establishes the opportunity to study these STIC lesions further to identify how early changes progress into cancer, and to develop better prevention and treatment options. Based on the discovery of these precancerous lesions and other findings, some researchers have theorized that perhaps all high-grade serous ovarian cancers may actually originate in the fallopian tubes
Arguments that support tubal origins of BRCA ovarian cancers include:
These arguments led some gynecologic oncologists to propose that interval salpingectomy — removing the fallopian tubes and leaving the ovaries intact until after natural menopause — might lower risk for ovarian cancer in high-risk women while avoiding the negative side effects and long-term health consequences associated with oophorectomy at a young age. After menopause women would then undergo a second procedure to remove their ovaries. But before the medical community can accept salpingectomy as a risk-reducing option, we need evidence that it is safe and effective. This requires a research study, optimally one that follows out hundreds to thousands of high-risk women for more than a decade, and compares outcomes of women who have salpingectomy, women who have BSO, and those who choose surveillance. The design of such a study faces several challenges. Some experts are reluctant to support such a study based on some valid concerns:
Despite these valid concerns, other experts make cogent arguments in favor of studying salpingectomy as a risk-reducing option for high-risk women, including:
Although our conference presentation on salpingectomy was set as a debate format, both presenters agreed on one important conclusion: the time is right for additional study of salpingectomy as a valid risk-reducing option. Still, questions remain about the feasibility of conducting such a study. Recently the Gynecologic Oncology Group, part of the National Cancer Institute’s Clinical Trials Cooperative Group Program approved further development of a study on salpingectomy. Development of study design could take months, and it may be more than a year before the study would open at GOG sites around the country. The purpose of this pilot study would be to further examine the fallopian tubes of high-risk women who undergo the procedure and to assess:
Preliminary results of a FORCE-conducted survey on attitudes of high-risk women towards participating in ovarian cancer risk-reduction research were presented at our 2011 annual conference. Almost one-third of the 333 respondents indicated interest in participating in a prophylactic salpingectomy study. The final results from our survey will be presented by researchers from MD Anderson Cancer Center as a poster at the Society for Gynecologic Oncology annual meeting in Los Angeles next month.
Stay tuned for further updates on salpingectomy research.
If you are a woman at high-risk for ovarian cancer and you have had your fallopian tubes removed but retained one or both ovaries, please consider participating in our salpingectomy research registry.
Domchek, SM et. al., Association of Risk- Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality. Journal of the American Medical Association; 304:967-975, September, 2010.
Carlson, JW, et. al., Serous Tubal Intraepithelial Carcinoma: Its Potential Role in Primary Peritoneal Serous Carcinoma and Serous Cancer Prevention. Journal of Clinical Oncology; vol. 26 no. 25: 4160-4165, September 2008.
Callahan, MJ, Crum, CP et. al., Primary Fallopian Tube Malignancies in BRCA-Positive Women Undergoing Surgery for Ovarian Cancer Risk Reduction. Journal of Clinical Oncology; vol. 25 no. 25: 3985-3990, September 2007.