Ovarian Cancer Study Provides Key Information, Raises Important Questions

S. Diane Yamada, MD

By S. Diane Yamada, MD

A study, published last week in the Journal of Clinical Oncology and receiving a lot of attention, is a large prospective study of 5,783 BRCA1 and BRCA2 mutation carriers – the genes that heighten the risk for breast and ovarian cancers.

It reports detailed information on the number of occult cancers found at the time of prophylactic salpingo-oophorectomy (removal of fallopian tube and ovaries) or oophorectomy, the annual risk of cancer in carriers who did not undergo such prophylactic surgery, the risk reduction afforded by prophylactic surgery, as well as the effect of prophylactic surgery on all-cause mortality.

The authors found that of those undergoing prophylactic surgery, 4.2% of BRCA1 and 0.6% of BRCA2 carriers are found to have cancer at the time of surgery.

The annual risk of developing ovarian, fallopian tube or primary peritoneal cancer in those who do not opt to undergo surgery goes up significantly after the age of 35.

The highest incidence rate for BRCA1 carriers was between ages 50-59 and for BRCA2 carriers, between ages 60-69.

The authors also report on the risk of developing primary peritoneal cancer after oophorectomy (0.20% for BRCA1 and 0.10% for BRCA2).

The use of prophylactic oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube or primary peritoneal cancer in BRCA1 and 2 carriers and a 77% reduction in the risk of all-cause mortality.

 IMPLICATIONS

This study provides us with important information that we can use to counsel our patients. Once a patient decides to undergo risk-reducing surgery, we can discuss the risk of finding occult cancer at the time of surgery and put some numbers to the risk of developing primary peritoneal cancer after risk-reducing surgery.

We also have data on the age range for the development of the largest numbers of incident cancers for BRCA1 and BRCA2 carriers that can help inform when risk reducing surgery should be performed for maximum effect.

This study corroborates previous studies demonstrating a significant reduction in the risk of developing of ovarian, fallopian tube and primary peritoneal cancer, but even more importantly, shows that prophylactic surgery can reduce mortality by 77%, presumably by decreasing the risk of development of ovarian and fallopian tube cancer as well as breast cancer.

IMPORTANT QUESTIONS TO CONSIDER

There is no doubt that prophylactic surgery is beneficial. This study does not tease out, however, whether these patients had salpingo-oophorectomy or oophorectomy performed and there are implications to knowing this information.

We now know that a fair percentage of cancers that develop in BRCA mutation carriers are fallopian tube cancers. There are quality of life implications for inducing earlier menopause by performing a salpingo-oophorectomy as opposed to a salpingectomy.

So, should the prophylactic surgery for a patient at the age of 35 be a salpingo-oophorectomy or a salpingectomy?

Do these procedures provide equal benefit in terms of risk reduction for cancer and mortality?

Is there a subgroup of patients where the hormonal effect of oophorectomy is more important than the risk reduction associated with removal of the organs at risk for development of cancer (ovaries and tubes)?

Is there a tipping point that needs to be considered that takes into account removing the actual organs at risk (ovaries and tubes vs. tubes only), the quality of life effect of earlier menopause (vaginal dryness, hot flashes, osteopenia, osteoporosis) and the increased risk of cardiovascular disease associated with earlier menopause?

How safe or advisable is hormone replacement therapy for a subset of these patients as earlier menopause does have implications for both cardiovascular risk and quality of life?

This study provides us with very important, detailed information that is critical in our discussions with patients. However, as we become increasingly more informed in this area, the nuances become increasingly more complex and I frequently find that a consultation simply to go over a surgical technique (prophylactic removal of the ovaries and tubes) is never a 30 minute discussion.

S. Diane Yamada, MD, is the Joseph Bolivar DeLee Professor of Obstetrics/Gynecology and Chief of the Section of Gynecologic Oncology at the University of Chicago Medicine. She specializes in the diagnosis and treatment of gynecologic cancers, and is the principal investigator at the University of Chicago for the Gynecologic Oncology Group (GOG), a cooperative clinical trials group supported by the National Cancer Institute.

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