Physicians may have a clearer understanding of the optimum age for prophylactic oophorectomy in patients with BRCA mutations who want to reduce their risk of ovarian, fallopian tube, and breast cancer
Ellen T. Matloff, MS, CGC
Physicians may have a clearer understanding of the optimum age for prophylactic oophorectomy in patients with BRCA mutations who want to reduce their risk of ovarian, fallopian tube, and breast cancer, according to a study published online ahead of print February 24, 2014 in the Journal of Clinical Oncology.
The study showed that waiting to undergo prophylactic oophorectomy until after the age of 35 significantly increased the risk of developing ovarian cancer for women with BRCA1 mutations. Moreover, women with BRCA1 or BRCA2 mutations with no cancer at baseline who underwent oophorectomy experienced a 77% reduction in their overall risk of death by age 70.
The study also demonstrated that women who harbor only the BRCA2 mutation do not appear to be at an increased risk by age 35 and can delay surgery until their 40s.
“To me, waiting to have oophorectomy until after 35 is too much of a chance to take,” Steven Narod, MD, professor of medicine at the University of Toronto in Canada and the study’s lead author, said in a press release. “These data are so striking histhat we believe prophylactic oophorectomy by age 35 should become a universal standard for women with BRCA1 mutations.”
In the study, 5783 women with either BRCA1 (n = 4473) or BRCA2 (n = 1310) mutations were selected from centers in Canada, the United States, Austria, France, Italy, Norway, and Poland. The women were asked to complete questionnaires about their reproductive history, surgical history (including preventive oophorectomy and mastectomy), and hormone use.
Among the 5783 women, 2270 did not have an oophorectomy, 2123 had an oophorectomy before the study began, and 1390 underwent oophorectomy during the study follow-up period.
After an average follow-up period of 5.6 years (with some women followed as long as 16 years), 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of which 68 have died.
The results of the study showed that oophorectomy reduced the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers by 80%. The authors of the study found that if a woman with a BRCA1 mutation delays prophylactic surgery until age 40, her risk of ovarian cancer is raised to 4%. The risk of developing ovarian cancer jumps to 14.2% if a woman with a BRCA1 mutation waits until age 50.
For patients with BRCA2 mutations, there was only one case of ovarian cancer diagnosed before age 50, the authors of the study said.
“These results could make a real difference for women with BRCA mutations, who face tough decisions about whether and when to undergo a prophylactic oophorectomy. For women with BRCA1 mutations, these results suggest that surgery should be performed as soon as it is practical,” Don S. Dizon, MD, a specialist in medical gynecologic oncology at Massachusetts General Hospital, said in a press release.
“Importantly, for women who will be undergoing this surgery early in life, it’s reassuring to see that it carries long-lasting benefits, substantially reducing ovarian cancer risk as well as total mortality risk.”
At the Miami Breast Cancer Congress held March 6-9, 2014, Oncology Nursing News sat down with Ellen T. Matloff, MS, CGC, to get her perspective on this study and its implications for BRCA mutation carriers faced with difficult decisions about prophylaxis.
Matloff, who directs the Genetic Counseling Program at the Yale Cancer Center in New Haven, Connecticut, urged caution when considering the findings.
What are some of your concerns about the reporting of this research by some media outlets?
We’ve actually known for more than a decade now that for BRCA 1 and 2 carriers who are at increased risk for ovarian cancer, removing their ovaries and fallopian tubes at a younger age makes sense. My concern with the way the data were reported is that it made it sound like age 35 is some sort of a magic age, and that all BRCA 1 carriers, specifically, should have their ovaries removed at that age.
That’s not accurate. We have some BRCA 1 carriers who have a family history that includes ovarian cancer before the age of 35. In those families, and depending on other factors for that patient, it may make sense to even consider some risk-reduction strategies before the age of 35.
In other families, and, of course, you can’t base [the decision] only on family history, we have women who aren’t done with childbearing, and they might want to wait until 36. If I had been watching those TV broadcasts, I might have thought, ‘35 is the magic number, 36 will increase my risk a huge way,’ and the answer is, we don’t know.
I would really recommend that all BRCA 1 and 2 carriers seek the advice of a certified genetic counselor, to sit down with them, to go over what mutation they carry in which gene, to take a very detailed fourgeneration personal and family history, and to review their options. If this patient has had 20 years of birth control pill use, we know that her risk of ovarian cancer is already likely greatly reduced. If she’s had her fallopian tubes removed, for example, she may have greatly reduced her risk of ovarian cancer. A more personalized approach than ‘let’s pick the magic bullet of age 35’ would be optimal.
What are some of the options in development other than oophorectomy for these women?
For BRCA 1 and 2 carriers we’ve known for a long time—and this also applies to the general population— that birth control pill use greatly reduces the risk of ovarian cancer. And, for most people, it’s a very safe medication to use. There are some contraindications, such as risk of blood clots, that patients need to discuss with their physicians.
There is also some research on the horizon. We don’t have definitive data yet, but it does appear that many ovarian cancers actually start in the fallopian tube, and research is looking at whether or not removing just the fallopian tubes and leaving the ovaries intact may reduce the risk of ovarian cancer, certainly in BRCA carriers, but even in other populations. We don’t yet have those data, but if that is true, we may get to a point where we could say to BRCA carriers, let’s remove your fallopian tubes by age 30, and if you’re not done having children, let’s extract your eggs, either freeze them individually or fertilize them and freeze embryos...and give these women options. And then we could go back when they are older, perhaps age 40 or older, and remove their ovaries when they are closer to menopause.
That research is still underway, but we are really hopeful that that will someday be an option for BRCA carriers.