
Genetic Test Led 7 Women in 1 Family to Have Major Surgery–Then the Odds Changed - bookofjoe
https://www.wsj.com/articles/seven-women-in-a-family-chose-surgery-after-a-genetic-test-then-the-results-changed-11576860210
======
stevehawk
The women used the information they had, and what science knew at the time, to
try and make an educated decision to protect their health. More information
has since been learned stating that they may not have needed to be as extreme
as they were, but ultimately they've still protected their health.

~~~
ineedasername
Precisely. This shouldn't be taken as an indictment against genetic testing
and acting on those results. Only that preventative actions and their
consequences should be balanced against the uncertainty present in this fairly
new field.

~~~
trentnix
How aware of the uncertainty were those “experts” who recommended they have
surgery? Was that uncertainty effectively communicated to this family? Surgery
carries risk and costs as well. And it’s becoming more likely that the risk
assumed by these women might have been needless. Is there no accountability to
be assigned at all because all is well that ends well?

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.

~~~
stevehawk
I'd bet the surgery was not recommended for some of them. BRCA isn't a death
sentence just because you've tested positive (assuming you haven't presented
with any symptoms). If you're in your 20s or 30s the "experts" usually tell
you to stay proactive on monitoring/medical appointments (self breast exams,
ultrasounds of ovaries/uterus, etc) until you're done having children. Once
you're done with having children you should consider a double mastectomy and
possible hysterectomy.

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".

~~~
Alex3917
Hysterectomy makes much more sense than double mastectomy. Breast cancer is
detectable and in most cases treatable, whereas ovarian cancer can't really be
detected until it's already fatal.

~~~
stevehawk
Mastectomy is the preferred treatment for a lot of breast cancers,
particularly BRCA. Otherwise the woman or man is likely to just be back in a
few years for treatment when they develop the cancer in a different spot.

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lalaland1125
One thing that might surprise people is how little we know about human
genetics and what individual mutations do. The main problem is that there are
many different variations, with so many of them being quite rare, that it's
very difficult to estimate the effects of individual mutations.

Luckily, there are a lot of good research projects that should help us
identify more variants more effectively:
[https://www.ukbiobank.ac.uk/](https://www.ukbiobank.ac.uk/) and
[https://allofus.nih.gov/](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/](https://www.omim.org/)
and
[https://www.ncbi.nlm.nih.gov/clinvar/](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.

~~~
vivekd
Yes, this is the first question that jumped out at me when I saw this article.
How accurate are these genetic tests? Can they give us a confident assessment
of reliability so as to allow us to meaningfully do a cost benefit analysis of
surgery

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whiddershins
This is the second article in two days on Hacker News about the topic of
people taking genetic testing too seriously.

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.

~~~
keanebean86
A year or so ago my sister took a dna test. Some other family members have
also taken the test. The results showed an inconsistency in mitochondrial dna.
My sister had a different kind than our cousins.

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.

~~~
stevenwoo
Cursory reading of the mitochondrial DNA test indicates there is a European
gene set bias built into some versions of it, and there is a non
straightforward hereditability with mtDNA (conceptually like chimera?)
[https://isogg.org/wiki/Heteroplasmy](https://isogg.org/wiki/Heteroplasmy) Did
yall eliminate those?

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snegu
When we got my son tested to see if there was a genetic cause for his hearing
loss, there was an incidental finding that he had a mutation that could lead
to Long QT Syndrome (an arrhythmia that can cause cardiac arrest during
exercise or emotional stress).

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.

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bookofjoe
[http://archive.is/7S89q](http://archive.is/7S89q)

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zozbot234
7 women in 1 family learn that option value
[https://en.wikipedia.org/wiki/Real_option](https://en.wikipedia.org/wiki/Real_option)
is a thing, and that simplified risk assessments should be evaluated with some
care.

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viburnum
Surgeons are like a three year old with a hammer, everything looks like a
nail.

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neonate
[http://archive.is/7S89q](http://archive.is/7S89q)

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jcims
I'm trying to sort out the reality of a closely related question. What are the
statistics around actual damage done by false positives from discretionary
screening? This is clearly a potential case, but obviously we won't ever know
for sure.

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/](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.

~~~
heavyset_go
I think the absolute biggest issue is that the feedback loops in diagnosis and
treatment are often insufficient, especially when patients are going to urgent
care clinics and ERs for their problems. Patients are constantly passed off
between nurses, doctors and specialists. When doctors diagnose and treat,
unless patients go out of their way to follow up in detail, they have no idea
whether or not their diagnosis and treatment plan was correct or not. The
effect is compounded because people are less likely to go back to a doctor
that misdiagnosed them, or failed to treat their problems adequately.

~~~
jcims
Definitely a need for some kind of open standard for EMR federation and
exchange as well as some kind of universal registry for patients to pin their
data to.

If your hospital is running Epic/MyChart, full records can be exchanged with
other hospitals electronically. No? Faxes.

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herodotus
This article is paywalled. There is a summary on reddit:

> 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.

~~~
bookofjoe
[http://archive.is/7S89q](http://archive.is/7S89q)

