Research on Fallopian Tube Surgery to Lower Risk
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:
- STIC lesions found in fallopian tubes appear to be “precursor” lesions that will develop into ovarian cancers. No similar lesions have been found in the ovaries of high-risk women
- STIC lesions have similar gene profiles as serous ovarian cancers.
- As many as 50% of women with BRCA mutations who have ovarian cancer also have lesions in their fallopian tube.
- Preliminary studies in cancer-prone mice show that removal of fallopian tubes prevents high-grade serous carcinoma of the ovaries—the type that women with BRCA mutations are most likely to get.
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:
- Although many cancers in high-risk women may start in the fallopian tube, we have no proof that the tubes are the source for all ovarian cancers. Pathology shows that some women with BRCA mutations who have ovarian cancer also have clear fallopian tubes. Researchers are concerned that salpingectomy will represent a partial and inferior surgical option to BSO.
- The benefits of salpingectomy are unknown. Even if the procedure lowers the risk for ovarian-type cancers, it’s unlikely to impact breast cancer risk. Meanwhile, well-documented benefits of BSO for mutation carriers include:
- reduction of ovarian cancer and fallopian tube cancer risk
- reduction of breast cancer risk
- reduction in breast cancer-associated mortality, ovarian cancer-associated mortality, and overall mortality
- Concern that women who remove their tubes only to avoid menopause will not return for additional surgery to remove their ovaries after they undergo natural menopause.
- Worry that removal of tubes could disrupt ovarian blood supply, thereby leading to menopause and negating a potential benefit of the surgery over BSO.
- Concern that offering salpingectomy, even in a research study with consent forms that clearly outline the risks, might be perceived by patients as an endorsement or suggestion that the surgery prevents ovarian cancer.
- Women can avoid menopausal symptoms and other unwanted health effects with BSO followed by hormone replacement. (Studies indicate that hormone replacement after BSO is safe for previvors.)
- Designing such a study would require a large, costly cooperative research effort that would take over a decade, thousands of high-risk women participating, and massive recruitment and follow-up effort.
Despite these valid concerns, other experts make cogent arguments in favor of studying salpingectomy as a risk-reducing option for high-risk women, including:
- A growing and compelling body of research suggests that many so-called ovarian cancers in mutation carriers begin in the fallopian tubes.
- Even if all ovarian-type cancers don’t start in the fallopian tubes, some do. Salpingectomy might serve as an “interval surgery” to manage and lower risk in high-risk women who are not ready for BSO and would otherwise opt for surveillance only, which the gynecologic oncology community recognizes as an ineffective strategy to reduce risk. Women in this category could benefit from salpingectomy surgery.
- Women who undergo salpingectomy can maintain their ovaries longer and avoid long-term medical consequences of surgical menopause.
- This type of large-scale study could provide information about development and prevention of ovarian cancer that could help to propel more research into better options for both women with BRCA mutations and those without.
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:
- immediate and long term complications of the procedure
- impact of the procedure on ovarian function
- the proportion of women who ultimately undergo completion oophorectomy
- feasibility of conducting a larger trial to determine impact of the procedure on cancer risk.
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.
Disclaimer: Health links are made available for educational purposes only. This information should not be interpreted as medical advice. All health information should be discussed with your health care provider. Please read our full disclaimer for more information.
This site has been made possible by a generous grant from Morphotek.