Genetic Test Led 7 Women in 1 Family to Have Major Surgery–Then the Odds Changed
wsj.com
wsj.com
Throughout my life, and ESPECIALLY in medicine, there has been constant change in understanding but never a shortage of confidence by “experts” assuring me we got it right this time.
But we live in the age of Google. Our ability to search the Internet tends to result in patients making horrific decisions. My wife is a breast cancer surgeon and has a late 20s BRCA patient that presented with a significant breast mass six months ago. She refused any of the advised treatments because she was breast feeding at the time and stated to my wife, with a straight face, she would simply cut out sugar because she read that helps. Obviously my wife told her otherwise. Same lady came back in recently to finally seek treatment and she has a 30cm mass now. She's not even a candidate for surgery anymore because you wouldn't be able to close the wound post-op. But hey, imagine what it would have been like if she had kept eating sugar, right? Silly "experts".
As for differing results, I've never heard of firms disagreeing about particular genetic markers. What I've seen are ill-defined correlation models that try to tie them back to geographical regions when that's just not a great idea at all. You have to separate the two: The ancestry stuff is much closer to pseudo science than the medical.
The first info was that she had up to an 84% risk of getting breast cancer by age 70. How big where the error bars? Perhaps it was 84% ± 83% but it was presented as it was 84% ± 1%.
Why did they rush to get operated?
Why did the sister not wait 2 or 3 years to have another children? It's not a minor thing. She could freeze eggs just in case.
Why did she not wait 2 or 3 years so the toddler was older? Raising small children is very difficult if you can't pick them up.
Why not something less invasive like regular mamographies?
In these cases it is very important to get a second and third opinion before a major irreversible surgery.
IIRC there wasn't any point where having a double mastectomy was recommend for people with BRCA who hadn't already been diagnosed with cancer.
Luckily, there are a lot of good research projects that should help us identify more variants more effectively: https://www.ukbiobank.ac.uk/ and https://allofus.nih.gov/ are the two most prominent ones. Hopefully those two projects should enable us to get a greater understanding and help us better risk profile patients.
For those who are interested: https://www.omim.org/ and https://www.ncbi.nlm.nih.gov/clinvar/ are the two main public databases for storing information about genetic diseases. If you ever get yourself sequenced, they can be quite handy.
It’s really sad to realize how much damage Americans have done to themselves based on junk science.
Science works, but it appears most people are in no position to figure out how to respond appropriately to scientific findings.
I don’t know what the solution is, but the pattern is tragic.
>I don’t know what the solution is, but the pattern is tragic.
There is ( very unfortunately) no solution, for the vast majority of people ( tragedy of the masses if you will). But a tiny minority who are more intellectually gifted can team up and pool their resources ( intellectual or otherwise ) to better their health by equipping themselves with useful information ( i.e what is not junk science ) and perhaps even training themselves medically if needed.
My personal peeve with this tiny minority is that they are often too individualistic ( by virtue of being independent thinkers) to team up.
Side note - the article was behind a paywall, hence could not read it, but genetic tests aside, my understanding is that in mainstream medicine this pattern of over/mis-diagnosis often happens leading to mis/over-treatment, where often the treatment is worse than the supposed disease.
When she first found out she could only find 2 explanations. A super rare, basically impossible, random mutation or my sister and cousins had different female ancestors.
My sister hoped for number 2. She imagined our grandpa having an affair that resulted in our mom. To avoid shame our grandma raised the love-child as her own. my sister and I have always felt out of place so this would certainly explain everything.
Turns out the dna test is just not great at distinguishing mitochondrial dna.
His particular variant was marked as "unknown significance," but the doctors recommended he go on beta blockers immediately. We wanted to hold off and examine if there was actually a problem, since his EKG was perfectly normal and we had no family history of issues.
My husband and I both got tested, and it turned out I also carry the mutation. I did a stress test which turned out normal, and based on that info, the variant was reclassified to "likely benign."
It seems like there's a tendency to jump to conclusions that any variant in a gene where pathogenic mutations have been found is going to also be pathogenic, but that's just not the case. I think the more people who get this testing done, the clearer this will be. For a long time, people have only been tested if they already have symptoms, which means they will be biased to identify pathogenic mutations.
My immediate family has two cases in which discretionary screening did or could have potentially have changed outcomes.
First case, I had purchased a $20 glucometer off of Amazon to just test my blood sugar. Device was stuffed in a drawer only to be found a year or two later. I gathered the family 'round to make a blood offering to medical science, and it turns out my youngest was over 2x the standard range. Follow up the next day and same, take her to the endo and she has Type I diabetes. The fact that it was detected before she went to the ER in full diabetic ketoacidosis was so unusual that I bet we told the 'discovery' story 20 or more times to nurses, two endocrinologists, her primary care physician and the folks at Medtronic. What the hell? This is a $.50 test that has good specificity and selectivity for something being wrong. +1 for discretionary screening.
Second case, my wife was complaining of abdominal pain for a few months. Her entire family hates going to doctors, but after much urging from me she heads to urgent care. They send her away with basically nothing. She develops a cough, goes back a month later, says the pain is from the cough and here is some cough medicine. Another month goes by and we end up in the ER because urgent care is closed. They do a CT and find softball sized masses on her ovaries. Two days later she is diagnosed with stage 3C ovarian cancer. Had someone taken the time to do an ultrasound or do her CA-125 tumor marker early on, this could have been detected sooner and possibly before she was stage 3. Two years later we're now probably a million dollars into medical treatments and she's still in the thick of it. Again, in my estimation this is a +1 for discretionary screening.
The part that confuses me is that if you look at articles, papers and interviews with doctors, you'll find what seems to be a prevailing attitude in the medical community that discretionary screening causes stress, over-treatment and negative outcomes. Not only that, it happens so often that the benefits really need to be studied closely before any action is taken. Then, of course, these studies fall behind treatment studies in priority and as far as I can tell, don't get prioritized or completed.
My pet theory is that, in the US anyway, the medical community has an innate sense that there isn't nearly enough capacity to handle all of the incoming cases that would result, and because you can't blame a doctor for someone getting diabetes or cancer, they are off the hook. I'll stop short of saying it's a conspiracy, but in my opinion there is clearly some parallel thinking going on.
Happy to be proven wrong, though.
Edit: Here's an example. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873201/
Summary of four large scale ovarian cancer screening trials >20K participants starting as early as 1987. Universal findings that TVS + CA-125 reduces staging at detection, which is one of the best predictors of outcome in ovarian cancer. Where is the clinical implementation? Reading through this it seems the perfect is the enemy of the good, and it's extremely frustrating. At $40 per TVS and $50 per CA-125, my wife's treatment so far could pay for 40 years of screening for 250 women.
Discretionary testing also change the balance of power: before, patients had to beg for tests, but it was the doctor actions that resulted in the miraculous diagnostics.
But if you come with a test result in hand that force them to action, a bit like a car mechanic, doctors are not the hero. You are - or random luck. They won't like that reduction in status.
Also, they can't CYA anymore. I had 2 people I know very well in a certain hospital for 2 very different problem - one this year, one last year. In both cases, the hospital very carefully avoided the one test that would force them to take action and operate on the patient.
After much pestering in one case, they relented and operated. In the other case, they didn't, so they could discharge the patient without health insurance. Dies the next month? Not their problem! They couldn't have known it was this specific issue as they didn't test for it. And they didn't test for it, because otherwise they would have had to provide the matching care to a patient admitted through ER.
Ignorance is bliss - for doctors and hospitals budgets.
I expect this sad case to be heavily publicized, as it frightens people just the way they want: tests are bad. Obey your doctors.
If your hospital is running Epic/MyChart, full records can be exchanged with other hospitals electronically. No? Faxes.
> An extremely sobering story about overtesting. A family was found to have a particular, rare BRCA mutation which led to the women (including those that wanted to have future children) to have have radical mastectomies and oophorectomies. A few months ago their particular BRCA mutation was downgraded from harmful to undefined -- moving one woman's lifetime chance of breast cancer from 86% to 20%. The laboratory that reported both the initial and follow-up numbers has 33 cases of this mutation -- 11 from this extended family.