Angelina Jolie told the story yesterday of her decision to have her ovaries and fallopian tubes surgically removed to reduce the risk of ovarian cancer due to the faulty BRCA1 gene she was born with. This follows a similar decision to undergo a double mastectomy in 2013 to reduce the even higher risk of breast cancer the mutant BRCA1 gene bestows.
As a human being, its hard not to feel enormous sympathy with her for facing such a decision – a thoroughly 21st Century decision that no-one ever had to face until the advent of molecular medicine. For centuries humanity has had to face the many adversities of life head on, but for the most part without much forewarning and even less hope of intervention.
The knowledge that certain mutations in this BRCA1 gene confer such high risks of cancer (as much as 87% chance over a lifetime for breast cancer and 50% for ovarian cancer) has the potential to be empowering or frightening (and perhaps both at the same time) in equal measure.
The interventions are hugely invasive. The surgeries themselves are major, and come with short-term risks. The hormonal imbalances that will result can change not only health but also the person. But perhaps hardest of all to quantify is the psychological and emotional impact.
In addition to sympathy for having to face such a decision, Ms Jolie also deserves admiration for her self-awareness and the clarity of her thinking that has allowed her to make such a clear choice – the right choice uniquely for her. Not everyone is blessed with such gifts.
That matters because we – all of us – are going to face these kind of decisions much more frequently in the future.
We hear from all sides about the benefits of personalized medicine – the product of refined molecular diagnostics that offer a glimpse into the future health of the individual. But Ms Jolie’s experience of personalized medicine highlights some of the challenges that also remain.
The biggest hurdle seems to be one of education. The default state of humans is to be pretty bad at understanding risks – and the output of all precision medicine algorithms is precisely that: an estimate of individual risk. While science can make the estimate more accurate, what it cannot provide is the calibration of what that risk estimate means to the individual. A 50% risk of ovarian cancer over a lifetime sounds, on the face of it, like a death sentence. But it needs some context. First and most importantly we have to remember we are all born with a death sentence. The only questions are when and how. Something like 33% of everyone alive today will suffer cancer in their lifetime.
Of course, BRCA1 mutations carry a material risk of an early death – and no doubt that influenced Ms Jolie’s decision (as it would likely have done for most of us). But the important point is that properly understanding the implications of the genetic diagnosis is a complex education process. It cannot be nicely packaged up into a single number or a simple decision.
And BRCA1 carries one of the larger risks associated with any single genetic marker. As molecular diagnostics are refined (as they are being at an impressive rate), that picture will become more complex still – and the decisions facing the “patient” ever more challenging.
How will those with less education, less worldly experience, less self-awareness than Ms Jolie cope? Will we create, in effect, a two-tier system in which those with the necessary wisdom see their lives enriched by being offered such challenging decisions, while others, less fortunate, suffer in the face of exactly the same information?
At the heart of the problem is the very personal nature of the decision. Doctors can only lay out the risks and the consequences of intervention. At what level of risk a particular intervention would be justified will vary enormously between individuals. In the end, it’s a decision only the individual can take. And there is likely a huge gulf in the ability and readiness of individuals to rise to that challenge.
The implications of wider applications of genetic testing in healthy individuals are not restricted to the impact on the individuals themselves. What about the healthcare system?
Ms Jolie is also fortunate enough to be able to fund whatever treatment she choses for herself. But most people are not so lucky. Surgical interventions are very costly, and we have to ask at what level of risk are they financially justified (a parallel challenge to that of the individual asking at what level of risk they are emotionaly justified).
No doubt some will argue that prevention is usually cheaper than treatment. Breast cancer care is very costly, so surgery to prevent it is surely economically justified. But that ignores the percentage of people who selected the intervention who would never have gone on to develop the disease, as well as the people who – despite the intervention – develop it anyway (surgical removal of ovaries and breast tissue cannot abrogate the risk of these cancers completely because the removal is always imperfect).
There is also a huge cash-flow implication: the preventive intervention has to be undertaken many years, even decades, before the disease would have emerged. Even if it is financially cheaper to prevent than treat, if precision medicine accelerate the need for expensive interventions in a whole generation of people, the already over-stretched healthcare systems in the Western world will break completely.
None of these are arguments against developing molecular diagnostics with ever-superior predictive powers. But society – and healthcare providers – need to adapt to their presence. That starts with better education on understanding risk estimates for our children. If even half of them turn out able to face such challenging decisions with the dignity and insight of Ms Jolie, the personalized medicine revolution will be a triumph rather than a earthquake.
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