BRCA1/2, prostate cancer, and the Angelina Jolie effect

According to an article in The Sunday Times in the UK over the weekend, a well-known surgeon in the UK is claiming to have carried out “the first” radical prostatectomy on a man with no other indicator for treatment except a BRCA2 mutation and a significant family history of breast and prostate cancer.

Whether this is really the first such case — and frankly we doubt it because we are aware of a very small number of other cases of prophylactic radical prostatectomy in men with a serious family history of metastatic prostate cancer, going back years — the claim by this surgeon, originally reported in The Sunday Times, but also discussed in a Medscape article today, makes the “New” Prostate Cancer InfoLink feel distinctly uncomfortable. Frankly, it seems to us to smack of self-promotion and scare-mongering.

It is absolutely the case that certain genetic mutations do seriously increase risk for aggressive forms of prostate cancer — and we have already discussed the recent article by Eeles et al. that has attempted to quantify that risk for men with BRCA1/2 mutations. It may also be the case that prophylactic treatment of some type is appropriate for a very small subset of men who carry the BRCA2 mutation and who have clear clinical evidence of aggressive prostate cancer associated with this gene mutation in their family. However, there are a lot of things that we don’t know yet (as is the case with breast cancer as well):

  • We don’t know that carrying the BRCA2 gene inevitably results in men having prostate cancer, let alone aggressive and potentially metastatic prostate cancer.
  • We don’t know that there is any need to carry out prophylactic treatment of any type for men who carry this gene; it may well be sufficient to ensure a rigorous monitoring strategy in such patients and treat them if there is clear evidence on early diagnosis.
  • We don’t know that a radical prostatectomy is the most appropriate method by which to treat such men at all.

What we do know is that the following type of statement, supposedly offered by the surgeon in question during his interview with The Sunday Times (but not actually included on the newspaper’s brief web report), is certain to put a high degree of fear into a large proportion of men with any family history of BRCA2 mutation:

Knowing you are a carrier is like having the sword of Damocles hanging over you. You are living in a state of constant fear. I am sure more male BRCA carriers will follow suit.

Is this really the right way to be offering men sound guidance about medical risk? The “New” Prostate Cancer Infolink thinks it absolutely is not. We also have an uncomfortable feeling that way more women than necessary will now be seeking prophylactic radical mastectomies as a consequence of Ms. Jolie’s decision to “go public” with her surgery.We are not criticizing Ms. Jolie for her decision, but the media reaction was distressing and unfortunate.

Decisions about radical prophylactic therapy of this type come with a range of complex medical and ethical questions that relate to risk and quality of life. This is serious business that involves risk for life and death (especially if something goes wrong with the surgery; people still do die quite regularly during “routine” surgical procedures). “Promotion” of the unproven “benefits” of prophylactic radical prostatectomy in the media feels distinctly questionable to those of us who still think ethical behavior is something we are meant to apply in our day-to-day lives.

5 Responses

  1. Sergey Brin, one of the co-founders of Google, had a prophylactic prostectomy based on family history/genetic tests some years ago. I can’t remember which genetic issue … I read about this in Francis Collins’ book on personalized medicine. It seemed a bit extreme to me when I read about it, but I’m sure Mr. Brin is a brilliant guy capable of making rational decisions.

    If Ms. Jolie was advised correctly (that she had an 87% chance of getting breast cancer), then her decision was certainly rational, if difficult. Most insurance plans will cover a prophylactic double masectomy for someone with Ms. Jolie’s family history/genetic test results. In addition, she also had access to the very best in reconstructive surgery. We have a family friend with the same conditions as Ms. Jolie who had this done. Interestingly my 87-year-old mother thought it was extreme, while my sister (a nurse) said if she was facing the same odds as our friend she would absolutely have it done.

  2. Two years ago (about 6 months before I even knew how to spell USPSTF), I wrote an opinion at an online prostate cancer support site that “prostate cancer awareness” was misguidedly focused on getting more men screened with the PSA test as a means to “end PC.”

    My tongue-in-cheek suggestion (on 4/10/2011) was that, “We could pretty much wipe out prostate cancer if we simply remove the prostate of every man at age 40.”

    Perhaps I was more prophetic that I realized … ?

  3. Dear Casey:

    Regarding your tongue-in-cheek comment about ending prostate cancer … if I may add some more information on how medicine could wipe out prostate cancer easier and cheaper …

    In an article entitled “8 signs you are at risk for prostate cancer” on The Prostate Net web site I enjoyed the following:

    — Men who have sex during their 20s and 30s and men that masturbated had a higher incidence of prostate cancer, but, if in their 50s have this behavior had a lower risk. Hmm, hold off and behave oneself till 50 and lower the risk.

    — Index finger shorter or same length compared to the ring finger – higher risk of prostate cancer. Finger length correlates to exposure to testosterone before birth,, and this exposure to testosterone controls the developement of sex organs … From my biology class in school, this hit of testosterone stimulates the body to form male genitalia and effects the brain to inform it that the body is male. If this does not occur, the brain does not know that the body is male and will/may treat it as female. … As for the maleness being developed, there are mixed signals to the developing cells and femaleness occurs or reduced maleness.

    Thus the only way to rid humanity of prostate cancer is to stop the development of males via any way possible. Since the male is “pre-disposed” to have prostate cancer in his life, and delaying “usage” till 50 or over appears to be unobtainable, society needs to get rid of male-born children to save itself from the future medical costs. … Of course, the remaining society would be only women and in time humanity would end. …

    This may be extreme, but it would be a “cure”.


  4. Mike: I would like to seek your counsel. …

    We lost a compatriot last week to the most aggressive prostate cancer Larry Fong says he has ever seen — the med/onc at Palo Alto Medical Foundation said the very same too. Neve was my Saturday morning Premier League buddy — he was also a fine rugby player at Merchant Taylors and Oxford, although a few years older than me so we never competed on the same field.

    A Foundation One test was ordered but never completed because he passed while it was queued. The family are wondering whether to run it for the benefit of his son who is 29 to see if mutations like you mention here are present.

    Neve was germline BRCA negative. The question I do not understand is the likelihood for somatic mutations to reoccur in offspring. And whether his son should at least be exploring prophylactic removal — or whether his Dad’s negative germline result makes this a redundant discussion.

    Neither you nor I are proponents of a prophylactic procedure. At the same time, Neve’s disease, when it recurred after surgery, was rampant, with PSA rising by 300 points a week at times. He topped out at 4,300.

    Thoughts …?

    Thanks and happy holidays to you and your family,


  5. Dear Rick:

    As far as I am aware, there is no reason to believe that a mutation occurring somewhere along the line in a patient with progressive disease (but not known to be present at diagnosis) is hereditary — even in a child who is subsequently diagnosed with prostate cancer. The reasons for initiation of such mutations are not well understood.

    Frankly, I have no idea what one should do in a situation like this. The people who might have a sensible suggestion are going to be people like Arul Chinnaiyan at the University of Michigan — although I doubt if even he could give a definitive answer to a question like this.

    The other thing that is important here is what I refer to as the “paranoia factor”. While your friend’s son is certainly at heightened risk for clinically significant prostate cancer, this doesn’t actually mean he will be diagnosed with this disorder. Only he is going to be able to make the decision about what he wants to do, and in all honesty I have to tell you that having pressure placed on him one way or other by family members and friends is probably not fair to him.

    It is extraordinarily rare for a single gene mutation to be the critical factor in the development of an aggressive form of prostate cancer. It is much more likely that such cancers are associated with a sequence of mutations over time i a man who is simultaneously susceptible to the effects of those specific mutations in that order. If your friend’s demise was caused by such a sequence of mutations, and it appears to be a rare sequence, then there are real questions about the probability that this would occur again — even if his son was to go through the same prior treatment sequence for a cancer diagnosed with similar initial criteria.

    Now if there had been several male members of your friend’s family that had succumbed to similarly aggressive forms of prostate cancer, I could see the logic of running the Foundation One test to see if one could identify the relevant genetic history. However, on the basis of a single patient (albeit a father) I am much less confident that this would be worth the effort.

    Perhaps there is a compromise position, which would be to ensure retention of the relevant biopsy specimen, so that the relevant genetic tests could be run later, should his son ever be diagnosed.

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