Expert Sheds Light on Important Variables in Preventive Surgery in Ovarian Cancer

Maurie Markman, MD

OncLive: Can you tell us a little about the timing of risk-reducing bilateral salpingo-oophorectomy (BSO) in BRCA heterozygotes?

When do you recommend a surgery or procedure like that be performed?

That finding is important, because one would certainly say, "Well isn't it great to reduce the risk of ovarian cancer?” Of course the answer is yes, but what about the negative aspects of removal of the ovaries in premenopausal women? Might there, for example, be an increased risk of death from heart disease because of the lack of estrogen now? There may be a risk of osteoporosis, and then pelvic fractures, and then pelvic fractures lead to complications, and that might lead to death. Looking at overall mortality is also a very important question, in addition to the question of the risk of ovarian cancer. Again, let the data show that the risk of ovarian cancer is reduced, as is the risk of premature death, and that is very striking.There's less definitive data there. The general recommendation today from a variety of expert groups would be somewhere between the age of 35 and 45. Obviously, the later the better, from the perspective of issues of surgical menopause, which is certainly not an insignificant concern from the perspectives of the loss of estrogen for a woman. As I said, there’s also heart disease, heart problems, osteoporosis, and the psychosocial and vaginal dryness perspectives. There are a lot of issues that are potentially very significant. They should not be downplayed. So this would be good somewhere between 35 and 45.

Say a 30-year-old patient comes in. Do you definitely avoid that direction?

The other important point is that there's increasing evidence now that BRCA1 and BRCA2 mutations are really quite different, both in terms of the lifetime risk of cancer and, in the case of the question I was asked, timing. So, it’s about when those cancers seem to appear, and there's pretty good evidence that BRCA2 mutations do increase the risk of ovarian cancer, but before the age of 50, it's very uncommon. The percentage of BRCA2 mutations leaving ovarian cancer before the ages of 40 or 50 is probably about 1% or less, whereas at age 50, it might be 10%. Women with BRCA1 mutations, 10% of them may develop ovarian cancer by the age of 50. Therefore, it's not unreasonable to suggest to a woman with a known BRCA1 mutation at age 35 that it is a reasonable time to talk about a performance of that procedure, and for a woman with BRCA2 abnormality, perhaps age 45, it is not an unreasonable recommendation. Obviously I'm not giving medical advice, and I'm certainly not saying I know the individual patient, but those are reasonable considerations for the woman, her family, her advisors, and for her doctors who are advising her.I should add that when I talk about the issue of surgery—and of course a woman who doesn't have cancer because we're not talking about cancer right now—an important point is the issue of if she's already had a child. Has she said now at this point that she's had her family? That's a very personal question. At 27 or 28, if she says she finished childbearing, the negative aspect on doing the procedure that early would simply be that that's a lot of years of surgical menopause, number one. Number two is that if we knew her family history was such that she actually had members of her family that had cancer that early, then other than that, it probably wouldn't be needed that early.

What are some of the most important things oncologists should bring up to their patients about this?

The biggest issue is that we know estrogen has a positive function in a woman, beyond the obvious in terms of childbearing, and if we all had a crystal ball, then we'd be a lot smarter, and the best we can do is just to do statistical probabilities. The question is that if we have a patient at 26 or 27 that says, "I'm really worried," and she has a family history of ovarian cancer, but it wasn't until the age of 60, then the odds are that she can wait longer.The issue is that the benefit can't be guaranteed. The problem is that the peritoneal lining is made up of the same cells that line the ovary, and of course that woman still has that gene, and whatever their environmental exposures are that might help cause that cancer are still going to occur. So even at best, there's an 80% reduction in the risk of the cancer, which is a tremendous difference, but it's not 100%. Secondly, surgical menopause is a concern. It's not only the physiologic effects of estrogen on the heart and on the bone, but it is the effects on the vagina. It's the psychological effects of interactions. Natural menopause is a process that's very gradual, and whatever effect there may be with the estrogen going away can be very different from woman to woman, but in general, the sudden removal of estrogen can have a much stronger, striking effect.

Several variables are important to consider when undergoing preventive surgery for ovarian cancer, including familial history and age, according to Maurie Markman, MD. In an interview with OncLive, Markman, national director, Cancer Treatment Centers of America, discusses appropriate timing for prophylactic bilateral oophorectomies, the impact of surgery on a patient's life, and the age at which surgery may be appropriate in this setting.Markman: The question that I was asked was about when would be the most appropriate time to consider a prophylactic bilateral oophorectomy in a woman who doesn't have ovarian cancer, but has a known BRCA mutation. There is, first of all, overwhelming evidence that the performance of this procedure will reduce the lifetime risk of ovarian cancer somewhere in the order of about 80%. In addition, there is more recent evidence to suggest that not only does it reduce the risk of ovarian, but it also reduces the risk of all causes of death by approximately 70% or 80%.