Reviewing the Options for Preventing Ovarian Cancer in High-Risk Women

Ilana Cass, MD

Ilana Cass, MD

For women with gene mutations that predispose them to ovarian cancer, prevention is extremely important. But what are the most effective and least invasive prevention techniques, and when is the best time in life to employ them?

Those issues were addressed by Ilana Cass, MD, vice chair of the Department of Obstetrics and Gynecology at Cedars-Sinai, during a June 9 talk at the 10th Annual Conference of Facing Our Risk of Cancer Empowered (FORCE) in Orlando, Florida. FORCE’s mission is to improve the lives of individuals and families affected by hereditary breast, ovarian and related cancers.

The Mysteries of Ovarian Cancer

Of the 22,400 new cases of ovarian cancer anticipated this year, 15% to 18% will be associated with mutations to the BRCA1 or BRCA2 genes, or to rarer gene mutations, but about 82% will be attributable to “just bad luck,” said Cass, who is also an associate clinical professor of health sciences at the David Geffen School of Medicine at UCLA.

To make matters worse for affected women, there are no reliable methods of screening for early disease, the doctor noted. The most promising techniques—testing blood for elevated levels of the protein CA (cancer antigen) 125 and performing pelvic ultrasounds—led to overtreatment in studies and did not save lives, she said.

It may be that ovarian cancer’s heterogeneity is one reason for the failed screening attempts, Cass said. The cancer includes many types that each behave differently.

Chemoprevention

Strategies used to prevent the development of ovarian cancer are the same in women with genetic mutations and those without.

In the nonsurgical realm, chemoprevention through long-term use of birth control pills is effective, has a low complication rate, and is appropriate regardless of someone’s level of cancer risk, Cass said.

She cited 3 studies that found an up to 50% drop in the risk of ovarian cancer with the use of the pills in women with or without BRCA mutations. One study showed that women must take the pills for more than 10 years to experience the full benefit, and another showed that the protections against cancer last 30 years.

The studies were conducted in women in their 20s and 30s, so it’s unclear whether the medication would be effective in older women, Cass said. She added that the use of birth control pills is associated with a slight rise in the risk for breast and cervical cancers, although she called that information inconclusive; one of the studies she cited found that the increased risk for those cancers disappears within five years of discontinuing the pills.

Surgical Options

In addition to chemoprevention, there are several surgical options.

Salpingo-oophorectomy, considered the prevention “gold standard,” is the removal of the ovaries and fallopian tubes, either through surgery or laparoscopy. Undergoing this procedure between the ages of 35 and 50 can reduce the incidence of ovarian cancer by 70% to 85%, Cass said. Furthermore, in mutation carriers, the procedure allows a close examination of tissue for early signs of ovarian cancer, and 8% to 11% of BRCA-positive patients who undergo it are found to have malignancies, Cass said.

Unfortunately, salpingo-oophorectomy can spark many other significant side effects: It increases overall mortality and heightens the risk for heart disease, cognitive impairment, Parkinsonism, osteoporosis and psychiatric symptoms. For these reasons, it’s been found that there’s no benefit to removing the ovaries of women under 50 who are at average risk for ovarian cancer and are already undergoing hysterectomies, she said.

There’s more debate, however, about whether the uterus should routinely be removed in at-risk women who are having salpingo-oophorectomies. While uterine cancer is very rare in BRCA mutation carriers who’ve had their ovaries and fallopian tubes removed, the cases that do develop in these women tend to be very aggressive. Nevertheless, Cass said, there’s not enough evidence to deem that concept a standard of care.

Bilateral tubal ligation, common as a contraceptive method after childbearing, can help to prevent ovarian cancer. In a number of studies, this technique that cuts or blocks the fallopian tubes but leaves them in the body was shown to decrease the risk of developing certain subtypes by one-quarter to one-third. It proved even more effective in women with BRCA1 mutations, dropping their risk by 50%, Cass said.

Salpingectomy: New evidence is pointing to the fallopian tubes as the site where most ovarian cancers develop, she said. Removing the tubes (salpingectomy) is safe, relatively inexpensive and does not alter ovarian function, and some retrospective studies indicate that it’s effective. So why not just perform salpingectomy as a preventive measure, leaving the ovaries in place?

While the idea is sound, there are no studies showing that salpingectomy saves lives when compared with the removal of both the ovaries and the tubes, Cass said. Short of a larger collection of convincing data, she said, doctors are prescribing salpingectomy as a “bridging procedure” that patients can undergo to postpone their ovary removal, which should take place between the ages of 40 and 50.

Cass added that, because some disease begins in the ovary, removing only the tubes would fail to prevent all ovarian cancers. Another complicating factor is that it’s difficult to completely remove fallopian tubes, because portions of them touch the uterus.