Reducing risk while leaving menopause for later

Women with BRCA1 mutations have a 39% risk of ovarian cancer compared to the general population’s risk of 1.3%, while women with BRCA2 mutations fare slightly better with a 17% risk, according to the National Cancer Institute. Breast cancer rates are similarly elevated.

“But here’s the good news,” says Denise Nebgen, M.D., Ph.D., associate professor of Gynecologic Oncology and Reproductive Medicine. “If you know that you carry a BRCA mutation, there are steps you can take to greatly reduce your chance of getting cancer. Knowledge is power.”

In women at high risk for ovarian cancer, the common prevention strategy is to remove fallopian tubes and ovaries after childbearing is completed — typically between the ages of 35 and 40.

“It seems drastic, but removing ovaries and fallopian tubes reduces the risk for ovarian cancer by 80 to 90%,” Nebgen says.

And there’s an added benefit, she says. Because the ovaries make the hormone estrogen, which fuels many breast cancers, removing the ovaries reduces breast cancer risk by 50%.

The downside is that removing the ovaries and their accompanying supply of estrogen plunges women into instant menopause and all the unpleasant symptoms that come with it, including hot flashes, vaginal dryness and painful intercourse, and may place them at a higher risk for developing cardiovascular disease and osteoporosis.

“It’s life-changing to have your ovaries removed 10 to 15 years before menopause would happen naturally,” she says.

Another option

Now, women participating in a first-in-the-nation MD Anderson clinical trial have a way to reduce their risk while leaving menopause for later: a surgery known as salpingectomy removes the fallopian tubes while leaving ovaries intact.

The technique is built on intriguing science that suggests most cases of high-grade serous cancer — the most common and lethal form of ovarian cancer — arise from the fallopian tubes rather than the ovaries. A scientific literature review authored by Karen Lu, M.D., chair of Gynecologic Oncology and Reproductive Medicine at MD Anderson, suggests that in the future, ovarian cancer may be described as fallopian tube cancer. The study was published in the April 2015 edition of Cancer Prevention Research.

“For about 30 years, almost everyone thought ovarian cancer arose on the surface of the ovaries,” says Nebgen, who works closely with Lu. “But within the last five years, we’ve come to understand that many genetic ‘ovarian cancers’ appear to start in the fallopian tubes. So removing these tubes may greatly reduce risk.”

Researchers were tipped off by two phenomena: First, women who practiced birth control by having their fallopian tubes tied developed ovarian cancer 50% less often than women whose tubes weren’t tied.

Second, the initial wave of surgeries performed on BRCA mutation carriers in the 1990s showed early evidence of cancer in the fallopian tubes but not in the ovaries.

Nebgen considers removing only the fallopian tubes as an intermediary step before later removing the ovaries, and recommends it only as part of a clinical trial.

“I tell women that salpingectomy is an interim measure we can take. Eventually these women will also want their ovaries out to decrease not only ovarian cancer risk, but also breast cancer risk due in part to the ovaries’ production of estrogen,” she says. “But having the tubes out early, and then the ovaries out later, can be a stop-gap that reduces risk in this window without initiating menopause.”

The MD Anderson trial, led by Nebgen and conducted through the High Risk Ovarian Cancer Screening Clinic, is following 80 BRCA-positive women who chose one of three paths: screening only, the recommended traditional combination of ovary and fallopian tube removal, or fallopian tube removal followed by ovary removal years later.

Nebgen suggests removing the fallopian tubes while sparing the ovaries may be appropriate for women who don’t plan to have more children, are below age 40 and are strongly opposed to the idea of immediate menopause, to the point of refusing the current risk-reducing surgery that removes both ovaries and tubes.

Young and invincible

As BRCA testing becomes more common, clinicians are encountering more and more women who have been blindsided in their 20s and 30s — in the prime of their reproductive life — by the knowledge that they carry a potentially life-threatening genetic mutation.

“They could dramatically reduce their risk of cancer with surgery, but some women simply refuse,” Nebgen says. “They want to keep their options open until they marry or until they have one or two more children.”

These women believe they’re invincible, Nebgen says, and don’t realize they’re gambling with their lives.

Unlike breast cancer, no reliable screening test has been developed to detect ovarian cancer. And because the disease produces no obvious symptoms, it remains undetected as it silently grows. Nearly two-thirds of ovarian cancers aren’t caught until they’ve spread beyond the ovaries to elsewhere in the body. By then, the five-year survival rate is 45% — far below the 92% survival rate for ovarian cancer that’s found and treated before it spreads outside the ovaries.

Evolving alternative

Exactly how much salpingectomy reduces cancer risk is a question yet to be answered. The procedure is fairly new, and Nebgen is quick to point out that proving its effectiveness will require multiple studies in the years to come.

This spring, MD Anderson became one of five institutions chosen to participate in a new Ovarian Cancer Dream Team funded by Stand Up to Cancer, an organization started in 2008 by film and media leaders to quickly translate lab research into treatments for cancer patients. Dream Team members will pool their different areas of expertise and work together to prevent ovarian cancer in high-risk women.

MD Anderson’s role on the team is headed by Lu, who this fall will be principal investigator of a new Dream Team-funded clinical trial that looks at fallopian tube removal in 350 women with BRCA mutations. The multi-site trial builds on Nebgen’s pilot study, which concludes as this larger trial gets underway.

“Dr. Nebgen is conducting a proof-of-concept study — a smaller-scale study that is confirming for us that women are interested in salpingectomy to reduce cancer risk and stave off menopause,” Lu says. “Now we’re ready to build on that initial research with larger studies that give us data on salpingectomy’s safety and effectiveness.”

Until then, Nebgen considers salpingectomy an option for women who say “absolutely no” to the recommended, more aggressive fallopian tube and ovary removal surgery.

“Salpingectomy is not yet the standard of care,” she says. “But it’s an evolving alternative.”

Read the full story in the summer 2015 issue of Conquest magazine.