Thursday, 16 May 2013

Angelina Jolie and prophylactic double mastectomies

Angelina Jolie, who has the BRAC1 mutation, has undergone a prophylactic double mastectomy and says that she has thus reduced her risk of getting cancer from “87% to 5%“. She was faced with a most dreadful dilemma, and has been praised for her courage and for her willingness to make her story public. It is likely that her example will lead to more women with BRAC mutations having both breasts removed.

Should they?

If I a similar mutation and was offered the prospect of reducing my cancer risk from 87% to 5% by having my testicles removed, and I, like Angelina, had lost family members to cancer, I might go ahead. However, I would first spend some time checking the statistics, and re-reading Gerd Gigerenzer’s masterly “Reckoning with Risk” and his more recent “Calculated Risks: How to know when numbers deceive you”.

The reason for my caution is that:
a) Most of us have difficulty with statistics
b) Most of us have a particular difficulty with percentages and
c) Most doctors have as much difficulty with numeracy as the rest of us, but are more likely to be over-confident.

One of the main problems is that doctors and journalists concentrate on relative risk reduction and not absolute risk reduction. The first compares two procedures in terms of their relative effectiveness at reducing risk, the second shows you the overall reduction in risk. It is not much use to reduce your relative risk if the absolute level remains very much the same.

Consider the results from an earlier retrospective study by Hartman et al. (1999) which gives deaths per 100 women in the high risk group:

Prophylactic mastectomy        1
Control (no mastectomy)        5

You can see that the rate of death in this high risk group (with BRAC mutations) in the women without mastectomies is higher than in those who had the double mastectomy. 

The Relative Risk Reduction is 80% (4 women have been saved, and 4 divided by 5 is 80%.

The Absolute Risk Reduction is 4% (prophylactic mastectomy reduces the number of women who die from 5 to 1 in 100, a saving of 4 women per hundred).

Now you can see why clinicians, researchers, drug companies and journalists prefer relative risk reduction percentages to absolute risk reduction figures. They usually look more dramatic, and make better headlines.

However, research has moved on, and Rebbeck et al. (2004) report on 483 women with BRAC mutations who had double mastectomies at average age 38 and were followed for 6.4 years.

Results Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries.
Conclusion Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.

Prophylactic mastectomy        2         
Control (no mastectomy)      49

The relative risk reduction is 47/49 is 95%
The absolute risk reduction is 49-2 is 47%

A clear result, wouldn’t you say? This study is in line with previous studies such as Hartmann et al [4] who evaluated the efficacy of bilateral prophylactic mastectomy in a retrospective cohort analysis of 639 moderate- and high-risk women who had bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Data from this study suggest that bilateral prophylactic mastectomy is associated with a 90% reduction in breast cancer incidence and mortality in women at high risk of breast cancer. In the only other study of BRCA1/2 mutation carriers to date, Meijers-Heijboer et al [6] reported no postbilateral prophylactic mastectomy breast cancers in 76 BRCA1/2mutation carriers after 2.9 years of follow-up, compared with eight breast cancers in 63 mutation carriers who did not undergo bilateral prophylactic mastectomy (P = .003).

Well, now we can make a number of points. Most studies concentrate on whether a woman is diagnosed with cancer again. However, cancers are increasingly treatable, and although the medication is thoroughly draining and unpleasant, so is a double mastectomy, and the latter is permanent. Furthermore, for those with BRAC cancer risks there are prophylactic medications available. Getting a diagnosis of cancer is not identical with dying of cancer.

The Rebbeck paper does not report on mortality figures. These are theoretically calculated for the next 30 years, but we do not know what improvements we may get in cancer treatment over three decades. On current trends it should improve significantly. Survival rates are 93% if it’s caught at the earliest stages and 88% at stage 1.

A Cochran review in 2004 concluded: Bilateral Prophylactic Mastectomy should be considered only among those at very high risk of disease. 

What Angelina Jolie appears to have done is reduce her chance of getting cancer by half, a very significant reduction, but at the cost of both breasts. She was understandably frightened of getting cancer, but she was not doomed, and other treatments are available.  

There is always a celebrity effect, but any woman considering a prophylactic mastectomy should look at the data carefully, and look at the human costs and benefits of all treatment options. Modern medicine is saving more of us from cancer, for longer than ever before, but it still throws up the most awful dilemmas.


  1. although the medication is thoroughly draining and unpleasant, so is a double mastectomy, and the latter is permanent

    This is a bit hard to follow. Are you saying that surgical recovery following mastectomy is roughly comparable to chemo side effects?

    And what do you mean "permanent?" Approximately nobody, at least in the US, has double mastectomy without reconstruction. Since reconstruction following mastectomy is the only high prestige kind of boob job for a plastic surgeon to do, you get very good plastic surgeons doing them, generally. Furthermore, you can get them reconstructed prettier (at least in clothes) than they were before.

    Really, you can think of the whole thing as a free, high-quality, non-status-reducing boob job with cancer risk reduction as a welcome side effect.

    As long as you do it after you are done having kids, what's not to like? You sound a bit like those dippy men who excessively romanticize boobs. An affect which led, for example, to the strange craze for lumpectomies, far ahead of all evidence that they were a good idea.

    The general point is surely a good one: relative risk is almost always the wrong way to report effect sizes:

    Q: What's an epidemiologist?
    A: Someone who thinks two times zero is a big number

    But you seem to be using as an example one of the few places where use of RR is not all that misleading.

    1. You are right. The phrase is hard to follow, and tries to cover too much. Chemo side effects are very unpleasant. Mastectomies carry all the usual surgical risks, and so does reconstructive surgery. I may have been too influenced by seeing some of the worst effects at a distance, in medico-legal work. I have seen the new data from the 2004 study in its most optimistic light, but it seems a big improvement on the 1999 picture.

  2. Gerd Gigerenzer’s “Reckoning with Risk” is one of the best books I've read in the last twenty years; "masterly" is spot on.