Does ovary removal prevent cancer in women with a BRCA1 or BRCA2 mutation?

The numbers and statistics in the following blog entry are almost guaranteed to confuse you.

The article under discussion here, in the Journal of the American Medical Association, is titled: "Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation." It appears in volume 296, pages 185-192. The original article is available only by subscription or from the authors. Information here comes from the abstract. Definitions are at the end of this entry if you need them.

The authors conclude:

Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

They also state, in the results:

The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003).

O.K., so, according to this article, if you have one of the BRCA mutations, and you have your ovaries and fallopian tubes removed, you can still get ovarian or fallopian tube cancer [???]. You are also still at risk for peritoneal cancer. The 80% reduction in cancer risk sounds pretty good, though. If I hadn't already had my ovaries removed (they didn't tell me whether they removed the fallopian tubes), I'd probably consider this surgery if I were found to have the BRCA1 or BRCA2 mutation.

But what do the study numbers tell us?

1. The study was retrospective--1828 patients with BRCA1 BRCA2 gene were identified from an international registry between 1992 and 2003. Because it is only 2006, it is possible that women identified for the study will develop cancer (or die) in the future--only these occurrences in the past were considered in the analysis of the results. We do not know what will happen to the current "survivors". Also, the abstract doesn't identify how many women were "lost to follow-up" (that is, have data only for part of the study period).

[By the way, those of you worried about genetic privacy, do you wonder what this international registry is and where it gets its data? I certainly do.]

2. The data for the women were first split into those who had no oophorectomy 783/1828 (43%) and those who did: 555 (30%) prior to the study period and 490 (27%) during the study period. O.K. 43 + 30 + 37 = 100%; so far, so good.

3. By the end of the study period, 32 of the 783 women who had not undergone surgery developed cancers [the abstract doesn't say what type, but ovarian, fallopian tube, or peritoneal is implied]. This is reported, not as 32/783 (4.1%), but as 1015/100 000 per year.

4. Of the women who had undergone surgery, eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy. This is reported in the abstract as 217/100 000 per year. The fraction 18/1045 (11 + 7 = 18 and 555 + 490 = 1045) is 1.7%.

5. If you compared 4.1% with 1.7% (over the short course of the study), you might say that among women with a BRCA1 or BRCA2 mutation, those who had no surgery (oophorectomy) were 2.4 times as likely to develop cancer compared with women who had prophylactic (pre-emptive) surgery (4.1 divided by 1.7). [Note that the wording is "as likely", not "more likely".]

6. If you compared the per-year numbers 1015 vs. 217, you could say 5 times as likely (1015 divided by 217).

7. If you did a "survival analysis" [as the authors did], you would find "The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003)."

So, which is the "real" number?

Just one more set of numbers: Only about 5-8% of women have a mutation in the BRCA1 or BRCA2 genes. Many sources report that mutations of the BRCA1 and BRCA2 genes give women a higher risk of developing ovarian cancer (15 percent to 54 percent), than women without the mutation.

So . . . do you have a test for BRCA1 and BRCA2? . If you find out you have one or more mutations in these genes, do you have the removal surgery? If so, have you now eliminated your chances of having ovarian, fallopian tube, or peritoneal cancer? The answer is, No.

The purpose of spouting all these numbers is to help you understand that news articles select the numbers that seem simplest to them; the deeper you dig, the more likely you are to wonder about the validity and practicality of those numbers.

Marie Godfrey, PhD

Definitions: Salpingo-oophorectomy--removal of ovaries and fallopian tubes. Peritoneal-- the peritoneum is a membrane that forms a sort of envelope around your abdominal organs and also lines your abdominal cavity