Managing cancer risks: population wide screening and individual strategies
I read with interest the recent recommendations from the US Preventive Services Task Force on BRCA 1/2 testing. The tl;dr is that they were expanding the population of women who are recommended to get screening for BRCA 1/2 mutations to include more people with either ancestry or familiar history that might indicate they could have a deleterious mutation. The theory is that by targeting genetic screening at women who are most likely to be at risk, you can allow them to act before a potential cancer diagnosis: generally through enhanced and more frequent screenings or by surgical interventions to remove the risky tissue (e.g. mastectomies, oophorectomies, etc.). The early data is pretty compelling - women who acted on information found through positive screening results had significantly reduced mortality from these cancers.
I wanted, though, to think about this on both a very high level and a very granular one. On the high level, there's a fundamental tradeoff when you get to large scale screening: Are you sure that every patient who tests positive should have an intervention to reduce their cancer risk? If you screen everyone, you might be doing more harm than good and carrying out a lot of costly, risky procedures with substantial side effects to eliminate a risk that hasn't yet turned into reality. If you only screen some people (those identified as 'high risk'), you're potentially limiting this issue, but we're still talking about a lot of women - in some populations, BRCA mutations are found in upwards of 2-3% of women, which still translates into a staggering number of potential interventions that may or may not end up being necessary. Now, it so happens that the numbers for most BRCA mutations are pretty awful - something like an 80% lifetime risk of breast cancer and a 40% lifetime risk of ovarian cancer. So the interventions might be warranted in the population. But what about cases where the evidence is more muddled? BRCA is also implicated in some other cancers (prostate, male breast cancer, IIRC pancreatic cancer) but the effects are much less stark. Should we push really aggressively to prophylactically address these cancers as well? Where do we draw the line?
This issue is going to get trickier once population wide whole exome sequencing becomes the standard of care (probably within a decade or two). Physicians are going to be faced with mounds of data, and everyone one of their patients is going to have some number of SNPs or the like that are linked - with varying degrees of evidence - to various diseases. Sorting through which mutations (or combinations thereof) warrant an intervention, enhanced surveillance, or nothing at all is going to be a daunting task.
On a much more granular level, the new BRCA recommendations meant that a large number of women in my social circle are now part of the recommended screening group. I've heard some really interesting upshots from their discussions on the issue and their interactions with medical professionals. Some seem to feel like they wouldn't do anything different if they received a positive result, so why bother? Others are practically planning their mastectomies before even getting the testing. So, I'll put it to you. Imagine you're given the information that you have a genetic mutation that dramatically increases the chances that you'll get a life threatening cancer in the future. Do you:
1. Do nothing.
2. Change lifestyle risk factors (like smoking) but do nothing else. This will reduce your risk some, but not dramatically - BRCA 1/2 are tumor suppressor genes, so any mutagen is going to be a problem.
3. Get much more frequent screenings to catch a cancer early. This has the advantages of being noninvasive, and will reduce your risk of death substantially, but if/when you do get cancer you're still going to have to go through some pretty arduous interventions to treat it. Also, some types of cancer (e.g. breast) are way easier to screen for than others (e.g. ovarian), so your mortality risk doesn't go down as much as you'd like.
4. Surgery, remove all of the offending tissue ASAP (or as soon as you finish childbearing). This is your best chance to reduce mortality, but it's also the most drastic with very serious side effects. There's the psychosocial aspects of removing the breasts (even with reconstruction, which has mixed results), potential side effects from removal of any lymph nodes, the early onset of menopause from removal of ovaries (with attendant implications for hormone therapy), etc. It's not fun by any stretch of the imagination. But it works really well.
So what would you do? How do you weigh the risks against the costs of each course of action? How should thinking through this on a personal level inform how we think about recommended screening and interventions on a population scale?
Personally I'm in favor of having as much information as possible, but I'm not really sure whether I'd opt for option 3 or 4. I'd lean towards 4 because with my background I have an unhealthy belief in the power of medical technology and interventions, but the changes this would cause to quality of life for decades are not to be ignored. Would our society be better off overall if everyone with a mutation that substantially increases cancer risk just removed the risky tissue? I'm not really sure.
