Finally a really good article about the hype that is targeted cancer therapy. From the time cancer genome sequences were first obtained we learned that this approach was a long way off and might never work. Except for drug companies. Who can make a bundle. It is one of the greatest science scams I've seen in my lifetime.. NIH leadership should be replaced. Hyping this approach has benefitted a few at the expense of real advances in cancer. Inexcusable.
1
Epidemiologists follow clear guidelines about when screening is justified for people without symptoms of disease. Physicians should follow similar guidelines for diagnostic testing of people with symptoms of disease.
Those guidelines for screening are:
Disease has serious consequences
Screening population has high prevalence of the condition
Not too many false positive or false negative results
Test detects disease before critical point
Test is safe – causes little morbidity
Test is affordable and available
Treatment exists and is not too risky or toxic
Treatment is more effective when started earlier
This article uses the term "testing", but also confused diagnostic testing with screening - "The ambiguities and disappointments play out in two areas: There is genetic testing of patients to see if they inherited mutations that predisposed them to cancer, and there is genetic testing of cells from the cancer to look for mutations that drive the tumor’s growth"
But the examples cited as problems would have been better addressed by some of the screening guidelines above.
Those guidelines for screening are:
Disease has serious consequences
Screening population has high prevalence of the condition
Not too many false positive or false negative results
Test detects disease before critical point
Test is safe – causes little morbidity
Test is affordable and available
Treatment exists and is not too risky or toxic
Treatment is more effective when started earlier
This article uses the term "testing", but also confused diagnostic testing with screening - "The ambiguities and disappointments play out in two areas: There is genetic testing of patients to see if they inherited mutations that predisposed them to cancer, and there is genetic testing of cells from the cancer to look for mutations that drive the tumor’s growth"
But the examples cited as problems would have been better addressed by some of the screening guidelines above.
The real crime is that most all of this data is being collected outside of clinical trials, so we continue wasting lives, valuable time and limited resources without learning a damn thing, but the companies billing for all this worthless testing are quite happy to keep this vicious circle alive and ill.
“We are trying to find avenues of hope that aren’t just avenues of hype.” Elizabeth E. Campbell, MD
When academic physicians are stumped, the so-called experts, practicing physicians aren't going to offer more reassurance on what a patient should do. As a physician, I'm excited about the possibilities of "personalized" medicine; however, at this stage of their development, I am dubious. Presently, there is more hype than hope! The take away message is that routine genetic testing should carry a strong warning "your results can be conflicting" buyer beware.
When academic physicians are stumped, the so-called experts, practicing physicians aren't going to offer more reassurance on what a patient should do. As a physician, I'm excited about the possibilities of "personalized" medicine; however, at this stage of their development, I am dubious. Presently, there is more hype than hope! The take away message is that routine genetic testing should carry a strong warning "your results can be conflicting" buyer beware.
1
Having just had a double lumpectomy, I can tell you that every single surgery a person has is that person's decision. Lawyers removed the ability for a doctor to say, "Yes, you need surgery", no mater what the issue is. I ask, "what would you do if it were your loved one?".
It is obvious we now have all the ingredients to bake a pie but don't know how to put them together and successfully deliver a good one to the table. There are a lot of missing pieces in this decision for any woman. Basically, we're only half way there.
It is obvious we now have all the ingredients to bake a pie but don't know how to put them together and successfully deliver a good one to the table. There are a lot of missing pieces in this decision for any woman. Basically, we're only half way there.
...all of which reminds me of how lucky I was to have listened back in 1989 to the then recommended guidelines to have a baseline mammogram at 35 ( I was actually 36 and terrified) and a follow up at 40...which revealed a small tumor but 16/35 positive lymph nodes. I had the lumpectomy, framed in the doctor's words as breast conservation, along with aggressive chemotherapy and what was considered very intense radiation. I had a new occurrence in the other breast in 2011, 18 years out, and it was determined to be a DCIS which also was removed by lumpectomy, and treated with radiation. And hope. I wake up every day grateful, trying to keep one step ahead of the Emperor of All Maladies. I was lucky to have good health insurance and great doctors. We need both.
4
This article should be a specific "wake up call" for genetic counselors and oncologists, and a general "wake up call" for medical schools to train health care providers on how to advise patients regarding genetic testing. This article reflects on the poor training or knowledge that many physicians may obtain concerning genetics and how to assess risk and use the information to advise patients. In any cancer therapy, there will be a risk of adverse effects.The crux of the problem is understanding whether a genetic mutation (variant) confers a particular phenotype; in this particular case whether a variant in a DNA repair gene could cause more potential harm than cure after radiation therapy. The first oncologist apparently did not have the knowledge to assess the risk and passed the fear of ignorance to the patient, who sought a second opinion. Genetic testing is here to stay and may have great benefit but physicians and genetic counselors need to be prepared on what to do with information once the test is ordered. Knowledge of some breast cancer-associated genes, such as BRCA1 and BRCA2, is clearly beneficial in assessing risk and/or treatment options and knowledge of others may be uncertain or of little benefit, at this time. Simply passing the results of the genetic test to the patient without a guide for risk assessment is not satisfactory.
2
Years ago, I was receiving dental treatment at a clinic attached to a dental school at a major university here, in New York City --
I received treatment from advanced students, under the close and watchful eye of their teachers, who were all professional dentists with years of experience...
At one session, my student-dentist noticed a small sore on the inside of my mouth and - being overly cautious - asked the supervisor to come and have a look --
After a few minutes of being examined by a couple of the supervisors, one of them said I had an infection and wanted to prescribe antibiotics -- however, the other dentist (his colleague) said it was just a minor irritation which would respond to a treatment of warm salt water over a few days...
I remember standing there as the two doctors began, at first debating - and then arguing on the proper course of treatment -- when suddenly someone said - "Why not give him the script, but let him try the salt water for a few days, and if it doesn't help, then he can fill the script and take the antibiotics?"
After a few minutes of silence and foot shuffling - and deciding how to best save face - I was given the script and told to try rinsing three times a day with warm salt water first, to see if that helped...
I left with the written prescription in my hand, and an appointment to return in a week --
After a few days of rinsing with warm salt water - the sore cleared up nicely and was never mentioned again...
I received treatment from advanced students, under the close and watchful eye of their teachers, who were all professional dentists with years of experience...
At one session, my student-dentist noticed a small sore on the inside of my mouth and - being overly cautious - asked the supervisor to come and have a look --
After a few minutes of being examined by a couple of the supervisors, one of them said I had an infection and wanted to prescribe antibiotics -- however, the other dentist (his colleague) said it was just a minor irritation which would respond to a treatment of warm salt water over a few days...
I remember standing there as the two doctors began, at first debating - and then arguing on the proper course of treatment -- when suddenly someone said - "Why not give him the script, but let him try the salt water for a few days, and if it doesn't help, then he can fill the script and take the antibiotics?"
After a few minutes of silence and foot shuffling - and deciding how to best save face - I was given the script and told to try rinsing three times a day with warm salt water first, to see if that helped...
I left with the written prescription in my hand, and an appointment to return in a week --
After a few days of rinsing with warm salt water - the sore cleared up nicely and was never mentioned again...
2
Reading the article and the comments, I realize what a terrible job we have done in communicating what we do. For those of you who read my nom de plume and connect it with a profit motive, I've lost you already. Bye for now; I hope we will have a conversation in the future.
As a physician who spends 80 hours a week developing cutting edge drugs, I have what I hope is a good perspective on the process. Genetic testing will be one of the great breakthroughs in cancer therapy, but at present there are as many questions as answers. Cancer is an *incredibly* complex group of diseases. We biologists understand precious little about how cells actually are controlled when they are working well, much less when the control goes awry. Henry Ford didn't make Teslas, and probably couldn't imagine them, or global warming, but mass producing cars has done a lot for the world.
There has been research on the question raised by Dr. Zagar; it seems to support Dr. Evans' position. It is surprising a group of doctors couldn't reach a consensus. When I was practicing, in the cases where patients wanted to be involved, I would try to help them explore their feelings about a bad set of options. Which of the risks would they be most comfortable taking?
Would I get genetic testing for me or my family? I'll answer that with a question: Will the result make a difference?
Would I give my DNA or tumor for analysis to improve outcomes in the future? Without any hesitation.
As a physician who spends 80 hours a week developing cutting edge drugs, I have what I hope is a good perspective on the process. Genetic testing will be one of the great breakthroughs in cancer therapy, but at present there are as many questions as answers. Cancer is an *incredibly* complex group of diseases. We biologists understand precious little about how cells actually are controlled when they are working well, much less when the control goes awry. Henry Ford didn't make Teslas, and probably couldn't imagine them, or global warming, but mass producing cars has done a lot for the world.
There has been research on the question raised by Dr. Zagar; it seems to support Dr. Evans' position. It is surprising a group of doctors couldn't reach a consensus. When I was practicing, in the cases where patients wanted to be involved, I would try to help them explore their feelings about a bad set of options. Which of the risks would they be most comfortable taking?
Would I get genetic testing for me or my family? I'll answer that with a question: Will the result make a difference?
Would I give my DNA or tumor for analysis to improve outcomes in the future? Without any hesitation.
8
I think some good take aways from the article. 1. Patients need to be their own advocate. ASK questions. 2. Talk to experts in the field. Remember, Medical Oncologist specialty is medicine, Surgical Oncologist is surgery, Radiation Oncologist is Radiation and Genetist is genetics. 3. As a patient, know your family history as you go through the process. And listen to the clinicians and put ALL the information together and make a decision that you as the patient are comfortable with.
1
To make decision based on evidence, there's got to be evidence. Unfortunately, the financial incentives of financing medical care in this country generally doesn't want to pay for information unless it provides a direct incentive for the developer of a drug, test or procedure. Scientific research of this nature is inherently socialist -- that is, its benefits are widely distributed and may not accrue in an unambiguously accountable way to its payers. Market ideology applied to medicine is invisibly depriving a lot of people the benefits of shared knowledge.
1
The discipline of system biology supposed to address this conflict by systematically studying the complex pathway dynamics of human cells. But till today, the complete knowledge of cell pathways is lacking - only an incomplete map is available. The effort to create computer models of cell to understand the effect of genetic mutation on cell dynamics is not yet fulfilled - as a result, the interpretation of genetic mutation remains black magic. To get the benefit of genetic mutation knowledge, we need a detail system biology model of cell pathways. The technique of modeling is known, what is lacking is the complete map of pathways. There is very little change in this area over last 15 - 20 years. The effort of NIH on this area is lacking - doctors have different way to solve problems than computer scientists or physicist or mathematicians.
This story highlights the complexity of genetic germline testing for cancer risk. It does not consider a future where functional genomics is considered. Imagine using tests prior to treatment to simulate the mutations in petri dishes with cells that harbor the mutation in question. This must also be part of precision medicine testing for the future.
My favorite professor in residency told me that I was the one who went to medical school and I was the one who spent six years in residency, not the patient. Though, in the end it really IS the patient's choice, the doctor, if data is available, should guide the patient. Unfortunately, despite good intentions, we often don't know what to do. Which is not the fault of anyone. That being said, patients also need to know that their Google search last week does not trump their physicians knowledge and experience.
18
How patronising! An intelligent, well-educated, sceptical patient has no more need to rely upon a Google search than they do on the arrogance of an uninformed medical opinion.
Google is handy to find user groups, but for academic research obviously one should not look to vanilla Google. To this end, there is Google Scholar (showing number of times a given paper is cited, very handy), PubMed and Cochrane reviews. In between, there is a plethora of medical websites such as eMedicine, WebMd, etc.
I also read unpublished PhD theses in human physiology and biochemistry that interest me. Further, with the aid of online translators and dictionaries, I read very slowly online academic papers in German, French and Italian.
My basic understanding of physics, mathematics, statistics, epidemiology, organic chemistry, biochemistry, molecular and cellular biology is superior to that of the average MD or medical specialist. I am also willing to spend far more time researching the specifics of any medical issue that affects a family member than the specialist who has to see another patient, and the. another, and then another, all in the course of a single morning.
Why, therefore, should I suspend my critical judgement when I walk into a consulting room? Just because you went to medical school -- and your prof say so?
Google is handy to find user groups, but for academic research obviously one should not look to vanilla Google. To this end, there is Google Scholar (showing number of times a given paper is cited, very handy), PubMed and Cochrane reviews. In between, there is a plethora of medical websites such as eMedicine, WebMd, etc.
I also read unpublished PhD theses in human physiology and biochemistry that interest me. Further, with the aid of online translators and dictionaries, I read very slowly online academic papers in German, French and Italian.
My basic understanding of physics, mathematics, statistics, epidemiology, organic chemistry, biochemistry, molecular and cellular biology is superior to that of the average MD or medical specialist. I am also willing to spend far more time researching the specifics of any medical issue that affects a family member than the specialist who has to see another patient, and the. another, and then another, all in the course of a single morning.
Why, therefore, should I suspend my critical judgement when I walk into a consulting room? Just because you went to medical school -- and your prof say so?
6
That may or may not be true. My husband almost lost his life because his cardiologist didn't know that with his condition of myelodysplasia he couldn't take certain blood thinners. Because we were up on it, we insisted on early blood tests. We were right. His blood count plummeted. The doctor washed his hands of the case, telling us he "didn't do blood work." Too complicated to relate here, we were finally able to get with a cardiologist who was able to help resolve the problem, but not before my husband was losing blood in his intestinal tract, nose bleeds, and extremely low blood counts.
My primary care doc stopped asking me to have mammograms in 2000 because I had been clear in all past tests and there was no cancer, breast or otherwise in my family. (It specialized in heart problems that I later came up with as well.) If I had not changed doctors in 2008, I would not have known I had breast cancer - 2B and in some of my lymph nodes. This primary care doctor is very well known and highly regarded so one would not expect such a lack of action. I subsequently wrote to him relating what had occurred and suggesting he remember to have all his women patients go for mammograms annually.
Patients in the end are responsible for their care, which includes choice of physicians, etc.
My primary care doc stopped asking me to have mammograms in 2000 because I had been clear in all past tests and there was no cancer, breast or otherwise in my family. (It specialized in heart problems that I later came up with as well.) If I had not changed doctors in 2008, I would not have known I had breast cancer - 2B and in some of my lymph nodes. This primary care doctor is very well known and highly regarded so one would not expect such a lack of action. I subsequently wrote to him relating what had occurred and suggesting he remember to have all his women patients go for mammograms annually.
Patients in the end are responsible for their care, which includes choice of physicians, etc.
3
What most people do not understand about Breast cancer is that it is not one disease but many different variations of a disease. What works for one person may not work for another. What is the best way to go one year, may be discovered to be a mistake years later.
Basically, it is a crap shoot....you take the information you are given and, as a non-physician, try to make the best decision for your particular life and situation. In many situations, even the treatments that worked for most patients may or may not work for you. It is a very individual disease, and , sadly, we are still in the dark ages when it comes to the treatment.
Genetic testing for familial mutations ( such as BRCA ) is still a valid way to go in order to know risk factors for yourself and your family members. For treatment of most Breast cancer, however, we are still basically in the dark and guessing at the future.
Being told you have breast cancer and then being given all your options is like looking into a crystal ball and choosing a treatment...you guess and trust to luck that you're making the right choice for you. Only in the future will you know whether you chose correctly or not.
Basically, it is a crap shoot....you take the information you are given and, as a non-physician, try to make the best decision for your particular life and situation. In many situations, even the treatments that worked for most patients may or may not work for you. It is a very individual disease, and , sadly, we are still in the dark ages when it comes to the treatment.
Genetic testing for familial mutations ( such as BRCA ) is still a valid way to go in order to know risk factors for yourself and your family members. For treatment of most Breast cancer, however, we are still basically in the dark and guessing at the future.
Being told you have breast cancer and then being given all your options is like looking into a crystal ball and choosing a treatment...you guess and trust to luck that you're making the right choice for you. Only in the future will you know whether you chose correctly or not.
My mother-in-law died from breast cancer in the Fall of 1975. A week before she called her daughter and the "boy she was with" into her bedroom, "I have two things I want to talk with you about before I go."
"First, I want to know if the two of you are going to get married." I was glad and honored. Her daughter was undecided at best. But, with her dad in the room, the moment seemed to call for me to ask for her hand.
"Second, I want you both to promise me you'll read the Gospel of John." Huh? She could have said Hammurabi's Code, and it would not have seemed weirder.
She died, but her diagnosis was a blessing to her children, grandchildren, and great-grandchildren for, going on, 41 years. Her diagnosis took the fog of "I'll think about that tomorrow" out of her mortality. She died young, and none of us in her family would ever have wanted that, but it made her serious in her pursuit of answers about what would be next.
Her daughter and I finally did read the Gospel of John. In it we found the love of God in Jesus Christ. We ended up serving many years in ministry, an adventure we never would have had without that holy moment in 1975.
"First, I want to know if the two of you are going to get married." I was glad and honored. Her daughter was undecided at best. But, with her dad in the room, the moment seemed to call for me to ask for her hand.
"Second, I want you both to promise me you'll read the Gospel of John." Huh? She could have said Hammurabi's Code, and it would not have seemed weirder.
She died, but her diagnosis was a blessing to her children, grandchildren, and great-grandchildren for, going on, 41 years. Her diagnosis took the fog of "I'll think about that tomorrow" out of her mortality. She died young, and none of us in her family would ever have wanted that, but it made her serious in her pursuit of answers about what would be next.
Her daughter and I finally did read the Gospel of John. In it we found the love of God in Jesus Christ. We ended up serving many years in ministry, an adventure we never would have had without that holy moment in 1975.
3
Doctors took my mother off tamoxifen because tests showed it didn't work after five years. She called me, hysterical with fear, but what could I say but repeat news reports? After she passed away, others studies showed I didn't have to be an orphan this young.
I don't want testing or treatment. When I read the enclosure of the last treatment they offered that showed a max six month survival rate for $1,000/week, she signed up for hospice and my oldest brother, the MD, called Family Services to have us (I was named as well) for undue influence.
I don't want testing or treatment. When I read the enclosure of the last treatment they offered that showed a max six month survival rate for $1,000/week, she signed up for hospice and my oldest brother, the MD, called Family Services to have us (I was named as well) for undue influence.
Medical research and progress will never be at the pace desired by a public addicted to a 24/7 news cycle. Cancer patients should be allowed to try experimental drugs without the added stress of insurance company monitoring. Clinical trials will continue and some knowledge will be gained by off label and and extraordinary usage.
They are allowed to try whatever they want, but it doesn't mean insurance companies (meaning ultimately everyone else) should pay for it.
1
What viable changes are necessary, and by whom, when gathering relevant, or irrelevant, data, which becomes information-knowing, doesn't lead to necessary understanding and even, at times, to insights, in order to make relevant decisions, implement them and to learn from the outcomes, in an evidence-informed culture?
In the case of the patient profiled in this article, Angie Watts, the doctors overlooked a very important piece of information. Not only did she have a genetic mutation, but she also had early breast cancer. Since only a small number of women in their 40s get breast cancer, it's quite likely that the mutation caused the cancer.
The doctors could have gotten further information by testing her relatives. . Do any of her relatives have the same mutation, and also have cancer?
The problem here is that doctors almost never understand statistics. The services of a statistician are needed. It wouldn't be necessary for a statistician to evaluate each patient. Instead, they would just need to do a type of calculation called a Bayesian analysis. The Bayesian analysis would tell us the chance that a mutation of unknown significance caused cancer, when cancer was diagnosed in women in a particular age group. In other words, the Bayesian analysis would tell us, ""If a woman is diagnosed with breast cancer at age 40 to 45 and has a mutation of unknown significance in her BRCA2 gene, what is the chance the mutation caused the cancer?" and "If a woman is diagnosed with breast cancer at age 46 to 50 and has a mutation of unknown significance in her BRCA2 gene, what is the chance the mutation caused the cancer?" and so forth.
The statistician would then write up the results in a paper. Of course, this wouldn't be helpful unless doctors actually read the paper.
The doctors could have gotten further information by testing her relatives. . Do any of her relatives have the same mutation, and also have cancer?
The problem here is that doctors almost never understand statistics. The services of a statistician are needed. It wouldn't be necessary for a statistician to evaluate each patient. Instead, they would just need to do a type of calculation called a Bayesian analysis. The Bayesian analysis would tell us the chance that a mutation of unknown significance caused cancer, when cancer was diagnosed in women in a particular age group. In other words, the Bayesian analysis would tell us, ""If a woman is diagnosed with breast cancer at age 40 to 45 and has a mutation of unknown significance in her BRCA2 gene, what is the chance the mutation caused the cancer?" and "If a woman is diagnosed with breast cancer at age 46 to 50 and has a mutation of unknown significance in her BRCA2 gene, what is the chance the mutation caused the cancer?" and so forth.
The statistician would then write up the results in a paper. Of course, this wouldn't be helpful unless doctors actually read the paper.
3
I disagree with your analysis. I am confident that doctors did take a family history in this case, and I would guess that it was unremarkable for breast cancer since it was not mentioned in the article. I also disagree that "doctors almost never understand statistics," because modern medicine is heavily based off of statistics from clinical studies. Furthermore, your assumption that doctors don't read papers is wrong.
It is common knowledge in the medical field that early forming breast cancer has a high risk of being caused by some type of genetic mutation. Bayesian analysis is a useful tool, however at the end of the day it will only give you a percentage of certainty that the cancer is caused by this specific mutation.
Whether or not this cancer was caused by the mutation she carries, DNA damage due to radiation therapy with a faulty repair mechanism poses a significant risk for new tumor formation; this is the primary concern. Furthermore, it renders the use of Bayesian analysis to determine the likelihood of cancer induction by the mutation limited.
It is common knowledge in the medical field that early forming breast cancer has a high risk of being caused by some type of genetic mutation. Bayesian analysis is a useful tool, however at the end of the day it will only give you a percentage of certainty that the cancer is caused by this specific mutation.
Whether or not this cancer was caused by the mutation she carries, DNA damage due to radiation therapy with a faulty repair mechanism poses a significant risk for new tumor formation; this is the primary concern. Furthermore, it renders the use of Bayesian analysis to determine the likelihood of cancer induction by the mutation limited.
1
Actually it just wouldn't be helpful at all. As an oncologist myself, I fully understand your point as well as the statistics, and your point is simply irrelevant.
If you know she is BRCA, you make recommendations based on the risk of BRCA (such as whether to remove ovaries to prevent ovarian cancer). Whether you can say 100% that the breast cancer was because of the BRCA is utterly unhelpful both to the patient, and to her family members. If they have the mutation, it doesn't matter whether you have a probability of the first cancer, it doesn't help them decide anything.
If you know she is BRCA, you make recommendations based on the risk of BRCA (such as whether to remove ovaries to prevent ovarian cancer). Whether you can say 100% that the breast cancer was because of the BRCA is utterly unhelpful both to the patient, and to her family members. If they have the mutation, it doesn't matter whether you have a probability of the first cancer, it doesn't help them decide anything.
While your lead paragraph reflects currently accepted truth about pre-menopausal breast cancer, there may be explanations other than genetic mutation. One of those was brought to light in the past year by multiple studies which have shown a very strong correlation between early childhood (including in utero, via maternal serum levels) exposure to ddt and pre-menopausal breast cancer (particularly estrogen positive, her-2 neu positive). The correlation is variously four to five-fold, depending on the study cited.
Knowledge is usually, if not always, better than ignorance. The process of genetic testing has no physical impact whatsoever. However, the results can provide a cure, or a direction, if not immediately, then in the future.
Enough results from genetic testing, of a specific condition, can encourage funding to research a cure at some future date.
And with the medical advances we now have, might it not be better to have a double mastectomy, and reconstruction, when testing (genetics and biopsy) indicates a cancer that might metastasize; rather than enduring a lumpectomy, radiation, and lifetime fear of recurrence?
Enough results from genetic testing, of a specific condition, can encourage funding to research a cure at some future date.
And with the medical advances we now have, might it not be better to have a double mastectomy, and reconstruction, when testing (genetics and biopsy) indicates a cancer that might metastasize; rather than enduring a lumpectomy, radiation, and lifetime fear of recurrence?
2
I pose a simple question, the answer to which is anything but simple.
In what areas of medicine will personalized genome-based medicine provide more cost-effective public health results than universal health care at the levels provided in those countries that have UHC?
Gina Kolata has offered us many scientifically fascinating individual case histories about personalized genome-based interventions of the kind that seem to have captured President Obama's attention. But her stories always have a hitch or two: 1) The interventions she describes are often very expensive, 2) Understanding the role of the gene in question can be a highly complex process.
Where in the field of public-health research are the studies that bear on my question? Can a few medical-professional readers give me some leads?
Only-NeverInSweden.blogspot.com
Dual citizen-USA-SE
In what areas of medicine will personalized genome-based medicine provide more cost-effective public health results than universal health care at the levels provided in those countries that have UHC?
Gina Kolata has offered us many scientifically fascinating individual case histories about personalized genome-based interventions of the kind that seem to have captured President Obama's attention. But her stories always have a hitch or two: 1) The interventions she describes are often very expensive, 2) Understanding the role of the gene in question can be a highly complex process.
Where in the field of public-health research are the studies that bear on my question? Can a few medical-professional readers give me some leads?
Only-NeverInSweden.blogspot.com
Dual citizen-USA-SE
The most neutral article I can recall reading from the usually dour Ms. Kolata.
True, evidence is currently lacking that this testing helps right now and even that early detection saves substantial person-years of life--a very hard thing to prove. Advocacy groups have the unhelpful habit of blindly believing in diagnostics and treatments without solidly proven benefit and that withdrawing financial support on this basis is tantamount to an attack on the underlying disease demographic. Some also believe in expending unlimited resources to save infinitesimal person-days of life.
As bitter a pill as it is for many to swallow, society should take a more rational approach to what it’s willing to spend on current diagnostics and therapy not yet demonstrated to save significant person-years of life, and to employ a concrete if arbitrary person-years/$ metric.
BUT, regarding RESEARCH into more effectively treating deadly diseases, I advocate a more liberal approach. Time and again important discoveries have fallen out of seemingly wildly unrelated research. Acquiring more knowledge I believe benefits us all in the end (nefarious aspects of human nature aside). Multi-decade setbacks or failure to advance is typical of the discovery process. This specific effort may not necessarily bear fruit, but I support continued effort in it among other things despite lack of clear current benefits because a decision to support only those things that appear immediately more promising is myopic.
True, evidence is currently lacking that this testing helps right now and even that early detection saves substantial person-years of life--a very hard thing to prove. Advocacy groups have the unhelpful habit of blindly believing in diagnostics and treatments without solidly proven benefit and that withdrawing financial support on this basis is tantamount to an attack on the underlying disease demographic. Some also believe in expending unlimited resources to save infinitesimal person-days of life.
As bitter a pill as it is for many to swallow, society should take a more rational approach to what it’s willing to spend on current diagnostics and therapy not yet demonstrated to save significant person-years of life, and to employ a concrete if arbitrary person-years/$ metric.
BUT, regarding RESEARCH into more effectively treating deadly diseases, I advocate a more liberal approach. Time and again important discoveries have fallen out of seemingly wildly unrelated research. Acquiring more knowledge I believe benefits us all in the end (nefarious aspects of human nature aside). Multi-decade setbacks or failure to advance is typical of the discovery process. This specific effort may not necessarily bear fruit, but I support continued effort in it among other things despite lack of clear current benefits because a decision to support only those things that appear immediately more promising is myopic.
1
It's really quite simple.
People need to be taught not to be afraid of information.
Information is our friend.
How we are able to validate, interpret, and act upon this information in the realm of of diagnostics and health management is inherently an iterative process.
There is essentially nothing different from a doctor administering a manual breat exam and feeling a suspicious lump and a doctor ordering whole genome sequencing and finding a genetic alteration.
Both procedures are an attempt to gather information so that a diagnosis can be rendered and a treatment plan initiated. IN both cases the information gathered must be interpreted properly. Not every mass is an invasive cancer, and not every genetic variant is pathogenic or clinically relevant.
As a society we must learn not to fear data. We must learn to analyze, manipulate, and validate data so that it becomes useful in bettering health outcomes and human happiness.
People need to be taught not to be afraid of information.
Information is our friend.
How we are able to validate, interpret, and act upon this information in the realm of of diagnostics and health management is inherently an iterative process.
There is essentially nothing different from a doctor administering a manual breat exam and feeling a suspicious lump and a doctor ordering whole genome sequencing and finding a genetic alteration.
Both procedures are an attempt to gather information so that a diagnosis can be rendered and a treatment plan initiated. IN both cases the information gathered must be interpreted properly. Not every mass is an invasive cancer, and not every genetic variant is pathogenic or clinically relevant.
As a society we must learn not to fear data. We must learn to analyze, manipulate, and validate data so that it becomes useful in bettering health outcomes and human happiness.
24
I agree with glorynine. I have BRCA 1 as do my 2 sisters. We found out because 1 sister was diagnosed with breast cancer at 40 (1st mammogram found tumor). That was in 2002. After lumpectomy, aggressive chemo and radiation and luck, she is still with us. In 2012, her oncologist recommended she get genetic testing because her breast cancer was a triple negative type. He felt it could help her make health care decisions. After much thought, she did in 2013. She had the BRCA1. She cried when I found out I had it too because of her experiences. But I feel she saved my life or at least will get me time. I had my ovaries, tubes, and uterus removed because there are limited ways to detect ovarian cancer early and I was 49. I now get breast MRI's in addition to the annual mammogram. I'm good with that approach, but could change my mind and do the bilateral mastectomy. My other sister that is BRCA 1 did the same thing - MRI and mammogram. Last spring MRI found a cancerous tumor that was deep in her chest wall and would not have shown up on a mammogram. She opted for double mastectomy. We feel in our case, knowing helped us make decisions. As for Clive's comment about the breast tissue left behind, we get it, and she will still have the MRIs. Maybe it buys her some time and reduces her risk. Everyone and every case is different. In my case, I am thankful I got tested and that I am able to have additional screening and know my current options.
1
I absolutely agree. I had a lumpectomy in 2008 and seemed to be doing very well. My cousin had a mastectomy a year or so before. We both took the same drug - femara afterwards. My cousin, with the permission of her doctor, discontinued femara at 5 years, thinking because she had a mastectomy and seemed to be doing so well. My oncologist thought I was doing very well at 7 years too. But first he suggested my banked tumor be tested. Good thing he did because the test came back indicating I was at high risk for the return of cancer.
My cousin's cancer has now returned with a vengeance. It is throughout her abdomen, ovaries, and elsewhere. In a desperate attempt to save her life, she is undergoing chemotherapy, followed by surgery, and then chemotherapy again.
Does the test mean the cancer is lurking in my body and ready to jump out again? Maybe yes. Maybe no. But at least I am prepared. At least I am continuing with the femara and am watchful of my diet and general health.
I want the facts. I want the truth as it is known today. I certainly don't want a paternalist physician shielding me from the known facts and risks. I accept the fact we all die and have little choice on how we are ushered out. This, by the way, makes some doctors very uncomfortable. They really don't like it much when they have a patient with some knowledge of the situation and possible solutions. Others regard themselves as my partner.
My cousin's cancer has now returned with a vengeance. It is throughout her abdomen, ovaries, and elsewhere. In a desperate attempt to save her life, she is undergoing chemotherapy, followed by surgery, and then chemotherapy again.
Does the test mean the cancer is lurking in my body and ready to jump out again? Maybe yes. Maybe no. But at least I am prepared. At least I am continuing with the femara and am watchful of my diet and general health.
I want the facts. I want the truth as it is known today. I certainly don't want a paternalist physician shielding me from the known facts and risks. I accept the fact we all die and have little choice on how we are ushered out. This, by the way, makes some doctors very uncomfortable. They really don't like it much when they have a patient with some knowledge of the situation and possible solutions. Others regard themselves as my partner.
My grandmother and mother died from breast cancer. My eldest sister was diagnosed with stage 4 breast cancer. The oncologist recommended genetic testing for my sister, at her expense. The results showed she carried the BRCA 2 mutation. She died, and the remaining 4 sisters were all placed under the care of the hereditary cancer umbrella of the cancer agency. We received genetic testing (free), gold standard mammograms and MRI's. My mammogram came back clear. One month later the MRI showed 3 tumors, confirmed upon ultrasound-guided biopsy. After a bi-lateral mastectomy the pathologist discovered 4 tumors. The tumors were not visible by mammogram and were not palpable, yet they were not small. The reason why, was dense breast tissue. Had my deceased sister not received the genetic test results, about a year later, I also would have been diagnosed with stage 4 breast cancer. I quickly received a mastectomy, chemotherapy and hormone therapy and 8 years later am alive and well. Two of my other sisters also were carriers of the BRCA 2 mutation and they had the bi-lateral prophylactic mastectomies and oopherectomies. My daughter is also a carrier and at the age of 40 will be undergoing the prophylactic mastectomy any month now. This testing has saved us from a horrible death from breast cancer or ovarian cancer and given us all a chance to live out a normal life span. I fully support this testing. It is important to have the right support behind you.
11
What a frustrating situation for these women.
This quote threw me a little:
“The results added nothing to her care,” Dr. Campbell said. “Nothing."
Yes, and that's unfortunate. Is this information being used to further possible research about those mutations in the future? As I grow older and have more experience with the medical field, I realize how much of these information that could be potentially life-saving seems to just go into the ether.
This quote threw me a little:
“The results added nothing to her care,” Dr. Campbell said. “Nothing."
Yes, and that's unfortunate. Is this information being used to further possible research about those mutations in the future? As I grow older and have more experience with the medical field, I realize how much of these information that could be potentially life-saving seems to just go into the ether.
Breast cancer testing, while sometimes of value, holds no guarantees about one's future.
This article reminded me of many other diseases that can be tested for (Huntington's, Duschene's Muscular Dystrophy), where medical science has yet to find a cure.
Life is like that. So, make the best of it.
This article reminded me of many other diseases that can be tested for (Huntington's, Duschene's Muscular Dystrophy), where medical science has yet to find a cure.
Life is like that. So, make the best of it.
1
Metastatic breast cancer. We're still left out, though 40,000 women and men die of metastatic breast cancer each year. In fact, one of my best friends, in her forties, is dying right now. Until there is a cure for metastatic breast cancer, there is no cure for breast cancer. Just more pink and hype.
1
The key problem with cancer care, not discussed in the article, is expectations. We expect that doctors will run tests, analyze the results, and tell us what to do, and that it will probably work. But that Marcus Welby, MD view of the medical profession has always been wrong. There has always been a large amount of guess work and uncertainty about cancer treatment. Gene therapy will not resolve those challenges in foreseeable future. It will always be the patient's responsibility to choose a treatment option where the outcome is uncertain. Our misplaced faith, our expectation, that we can rely on doctors to give us answers, makes the process of dealing with cancer that much harder.
You are in charge of your treatment, not your doctor, you need to make decisions and you need to be at peace with the fact that you will make the best possible decisions you can with the data you have.
You are in charge of your treatment, not your doctor, you need to make decisions and you need to be at peace with the fact that you will make the best possible decisions you can with the data you have.
3
It is not only reasonable, but required, for a physician to say "It's your decision" when (a) the technical facts are clearly explained and (b) it is a matter of competing priorities, one's personal risk aversion, quality of life vs possible prolongation of life, etc. In that case, it is clearly up to the patient to decide which option is best for them (or, perhaps, "least worst"). This is a great improvement over the previous era when the physician "knew best", and decided without involving the patient.
But it is unreasonable, and ought to be acknowledged as improper care, for a physician to say "It's your decision" when the decision rests on interpreting complex technical information.
In those cases, the move away from paternalist physician to "equal team member with the patient" is a major cop-out.
But it is unreasonable, and ought to be acknowledged as improper care, for a physician to say "It's your decision" when the decision rests on interpreting complex technical information.
In those cases, the move away from paternalist physician to "equal team member with the patient" is a major cop-out.
15
Genetic predisposition. Genetic testing. Enough..already! Science is galloping ahead of the practicalities. Knowing you have two breast cancer genes BRAC 1&2 isn't that helpful. Yes. You can undergo a bi-lateral radical mastectomy but even then tumour growth can reappear in the tissue on the chest wall. And the distress & the cost? Then a suggestion last week of 'a test' for risk for alzheimers? So. what then? Panic for the patient and the family? Neurosurgical intervention? Drugs? There are no realistic options. Its similar to the so-called promises (false) in the 'screening' test for Prostate Cancer - PSA. Over sold and then disendorsed by agencies including the American Cancer Society. Result? Too many incontinent & impotent men who were just over treated. Proceed with caution.
12
Better to know or not know? A tough choice. I agree that we seem to be stumbling around with the information genetic testing provides us. But it will sort itself out over time. However I disagree with your remarks about PSA testing for prostate cancer. That was hysteria created by the US Preventative Services Task Force, a body of "experts" that dissed PSA testing but did not include a single urologist on their board. If you think that genetic testing serves big Pharma, then that task force serve the insurance industry. If cancer spreads beyond the area of treatment, then that is the risk we cannot avoid. But do nothing? Your statistics, my life.
Cancer patients are under tremendous emotional and physical pressure. My
suggestion is to refer to the NATIONAL CANCER COMPREHENSIVE NETWORK
(NCCN GUIDLINES). These guidelines are available on the internet, and are free.
There are various sections for physicians and patients. The 26 most prominent
institutions in the U.S. are premier members. Memorial Sloan Kettering, Dana Farber, Fox Chase, Duke Cancer Center, M.D. Anderson, etc. These guidelines are revised when new drugs or methods are developed, In short,
the patient has to understand the strategies and plans of the physicians. These guidelines are critical for raising the level of understanding of cancer
medicine.
suggestion is to refer to the NATIONAL CANCER COMPREHENSIVE NETWORK
(NCCN GUIDLINES). These guidelines are available on the internet, and are free.
There are various sections for physicians and patients. The 26 most prominent
institutions in the U.S. are premier members. Memorial Sloan Kettering, Dana Farber, Fox Chase, Duke Cancer Center, M.D. Anderson, etc. These guidelines are revised when new drugs or methods are developed, In short,
the patient has to understand the strategies and plans of the physicians. These guidelines are critical for raising the level of understanding of cancer
medicine.
1
Genetic testing is not done in a haphazard fashion and, in the case of many cancers, can provide useful data that can significantly impact clinical management and therapy. The development of effective genetic testing is going on throughout the country, mostly at academic research centers, rather than "big pharma" (drug companies typically don't want to exclude any potential customers for their drugs based on a genetic test). The reason that the oncologists are unable to provide an accurate assessment of the impact of the mutation on the outcome of radiation therapy reflects the current lack of data on the outcome of such therapy with individuals that have such mutated genes. Academic cancer centers throughout the country are actively collecting exactly this type of information on patients, mutations, and treatment outcomes so that meaningful answers can be provided in the future (probably within about 5-10 years). Until the databases are fully developed, the clinical significance of many mutations will be unknown. In the meantime, geneticists (such as myself) and clinicians confront difficult ethical issues when deciding what genes to test and what data to divulge to patients and their families if they information is not clinically actionable. For example, should the family be told if a BRCA1 mutation is detected in a male child with leukemia? These issues are being actively discussed and policies are being developed, but the correct decision is usually not obvious.
9
It is the patient's information, how dare you withhold it?
1
From the article: "Dr. Norman Sharpless, the director of the Lineberger Comprehensive Cancer Center at North Carolina, estimates that perhaps one in 1,000 women with advanced breast cancer will benefit from using the approved and experimental drugs available today." Well, that sounds about right. My rough estimate for treatment of early stage breast cancer is that it helps about 1 in 10 patients who undergo it -- if that. The numbers tend to be astonishingly low. Which means that the treatments do not help about 9 out of 10 patients who undergo them -- and many suffer harm from these treatments. It's a conundrum, all right. And yet, for some reason, every patient treated thinks that the treatment saved her or his life. If only.
9
At 74 i find it more and more important to look very carefully at the so called "foods" we are consuming. As we age our liver has more difficulty in processing the folic acid (a chemical) that is put into 100% of all breads. In addition it seems that at least some if not all of this folic acid is sourced in China???
My answer is to replace all of it with bread made from fresh ground organic wheat berries. At least in my case it offers a host of benefits.
My answer is to replace all of it with bread made from fresh ground organic wheat berries. At least in my case it offers a host of benefits.
You are so lucky to have lived a long and healthy life. Unfortunately, cancer is a complex disease. Wheat berries is not a cure.
According to cancer.org "It has been estimated that as much as one-third of all cancer deaths in the US are related to diet and activity factors." Although genetic tests can lead to treatment dilemmas, they can spur serious and immediate lifestyle changes that could give you more of a fighting chance.
7
The vast majority of cancers are caused by old age. Since being old is not a lifestyle, it is not possible that one-third of cancer deaths are caused by lifestyle.
Studies that claim a high proportion of disease is caused by lifestyle almost always have the same flaw. They take physiological conditions, such as high blood pressure, and call them "lifestyles." Once you start doing this, almost any disease can be blamed on the patient's "bad lifestyle."
I have severe illnesses, including a hereditary cancer symptom, and I am sick and tired of my health problems being blamed on my supposed "bad lifestyle." (Pardon my churlish tone, but I am having quite a lot of pain at the moment from my double mastectomy.)
Studies that claim a high proportion of disease is caused by lifestyle almost always have the same flaw. They take physiological conditions, such as high blood pressure, and call them "lifestyles." Once you start doing this, almost any disease can be blamed on the patient's "bad lifestyle."
I have severe illnesses, including a hereditary cancer symptom, and I am sick and tired of my health problems being blamed on my supposed "bad lifestyle." (Pardon my churlish tone, but I am having quite a lot of pain at the moment from my double mastectomy.)
2
According to a New York Times article on April 21, 2014, by Dr. George Johnson, "One source after another promotes the protective powers of “superfoods”, rich in antioxidants. But this is nutritional folklore that is simply not supported by science. During the last two decades, the connection between the foods that we eat and the cellular anarchy called cancer has been unraveling string by string. There are a few hints that coffee may lower the risk of some cancers and that there are some possible benefits of vitamin D. Beyond that, there isn’t much to say. The relationship between consumption of red meat and colorectal cancer is so weak that a man who eats 1/3rd pound of meat per day only raises his chances by 1.71% from 1.28% over the next decade. Science has simply been unable to prove a direct connection between diet and cancer."
So, while it makes great sense to eat carefully and to exercise daily (as I do), the science is not be clear about the cancer fighting benefits. Such assertions leave cancer patients feeling that they are at fault for their cancers, when the science remains unclear.
So, while it makes great sense to eat carefully and to exercise daily (as I do), the science is not be clear about the cancer fighting benefits. Such assertions leave cancer patients feeling that they are at fault for their cancers, when the science remains unclear.
1
Yes, that may be true of lung cancer, for example, but it has nothing whatsoever rot do with breast cancer. All your comment does is, once again , blame the victim...not helpful, scientific, or to the point in this article about Breast Cancer specifically.
1
How is this different than when it was a blind "either or" decision? At least with data you have eliminated the "known" and actionable genetic information and treatment protocols. Having had a family member with a completely rare and statistically incredibly unusual medical occurrence (no clear diagnosis, no treatment path, no long term prognosis, and no billing code), what this article does not mention is that many cancers have uncertain paths of treatment. Welcome to real science. Anxiety is brutal but it is also our history--universal fear of disease. We have been conditioned to think a visit to the doctor equals a cure.
12
There is one very actionable genetic condition - Familial Hypercholesterolemia (FH). FH is a common inherited dominant genetic disorder - passed from parent to child - that affects the liver's ability to manage the cholesterol it produces causing very high LDL cholesterol (LDL over 190) from birth. This lifetime exposure to extremely high cholesterol too often leads to early heart disease - even in one's 20s, 30s, 40s. You can test genetically, or you can look at the results of a simple blood test for cholesterol and family history. People with FH usually have stories of generations of family members undergoing bypass, having heart attacks, or dying too young from heart disease. Unlike some other genetic disorders, FH is treatable with relatively simple interventions including medication, but less than 10% of people with FH are diagnosed. Knowing they have a genetic disorder, people can make an informed decision about how to manage their risk for heart disease and hopefully prevent it. Some will decide not to treat, but at least that's their informed decision. This is a hopeful example for the potential of personalized medicine for the prevention of heart disease for 1.3 million Americans.
6
We know a lot, but we don't know enough. This is frustrating for patients, but I prefer my doctor to be honest with me about what is known and what isn't known.
Someday, maybe, genetic screening will give a statistically useful key to what therapies are best. Not there yet.
Someday, maybe, genetic screening will give a statistically useful key to what therapies are best. Not there yet.
10
I have not had to deal with this personally, but have walked with others going through it. It seems to me that if a woman is fully informed about what genetic testing does and does not offer, many women would be willing to take it. It might indeed be of benefit to the individual, but it also offers the chance to participate in knowledge gained. Advances in medicine are made through courageous decisions of thousands of patients contributing to the process even when they themselves may not benefit.
16
Only if this goes in tipi some research database or registry. Most testing, such as Ms. Watts's presumably, is not done as part of a study. So where is her experience and that of others recorded? How are we building the evidence base?
2
That's exactly what I wondered above. I am dubious that it is--but it obviously should be. Otherwise, it's a complete waste for those who don't get an answer, and a waste for others getting that same result in the future.
There's a little mixing of apples, oranges, and peanuts in this discussion.
Yes, results from genetic tests are not always clear indications for anti-cancer therapy, and that's certainly not limited to breast cancer. The example of BRCA1/2 germline variants of unknown significance is related to risk of future disease, less so therapy decisions for current disease. Not only is there no therapeutic that targets BRCA1/2, one wouldn't even work - the gene is present in all cells in the body. Targeted therapy like Herceptin, Gleevac, and Tarceva are given to patients whose tumors express proteins that their healthy cells don't have, hence they "precisely" act upon the cancer.
Per COSMIC, the two somatic mutations of highest prevalence in breast carcinoma are PIK3CA and TP53, both of which are the focus of much ongoing research. One of the reasons it's so important that patients join clinical trials is that with rare mutation variants, there simply isn't enough data yet to determine if they're deleterious or benign, and if the former, whether they're responsive or resistant to therapeutics. Not getting genetic tests is a bit of Catch-22: if we don't know what the drivers are, we can't build drugs that target them, and can't tease out which drugs work for which specific variants. It's not magic, and it's not easy.
Yes, results from genetic tests are not always clear indications for anti-cancer therapy, and that's certainly not limited to breast cancer. The example of BRCA1/2 germline variants of unknown significance is related to risk of future disease, less so therapy decisions for current disease. Not only is there no therapeutic that targets BRCA1/2, one wouldn't even work - the gene is present in all cells in the body. Targeted therapy like Herceptin, Gleevac, and Tarceva are given to patients whose tumors express proteins that their healthy cells don't have, hence they "precisely" act upon the cancer.
Per COSMIC, the two somatic mutations of highest prevalence in breast carcinoma are PIK3CA and TP53, both of which are the focus of much ongoing research. One of the reasons it's so important that patients join clinical trials is that with rare mutation variants, there simply isn't enough data yet to determine if they're deleterious or benign, and if the former, whether they're responsive or resistant to therapeutics. Not getting genetic tests is a bit of Catch-22: if we don't know what the drivers are, we can't build drugs that target them, and can't tease out which drugs work for which specific variants. It's not magic, and it's not easy.
9
You say that, "The example of BRCA1/2 germline variants of unknown significance is related to risk of future disease, less so therapy decisions for current disease." However, your post is incorrect. PARP inhibitors such as olaparib, are specifically useful for BRCA1/2 mutated patients who develop ovarian tumors: https://en.wikipedia.org/wiki/Olaparib
Actually, the results of some genetic tests CAN affect treatment of already-diagnosed cancer. I was diagnosed with stage 1 invasive ductal breast cancer, had a successful lumpectomy, and was planning my radiation treatments, when my oncologist noted that though I had no family history of breast cancer (85% of patients have no such history) I hadn’t specified my ethnicity. When I told her “Ashkenazi Jewish, both sides,” she said that despite being older at diagnosis w/o family history, my ethnicity and a confirmed b.c. diagnosis did raise the question of BRCA 1 & 2 mutations, which increase the chances of future breast as well as ovarian, pancreatic, colon, uterine and melanoma cancers. Had I either mutation, radiation would have been inadvisable--I would have needed bilateral mastectomy instead, and reconstruction of irradiated breasts is limited to using one’s own tissue from elsewhere on the body (a long, painful surgery with a risk of complications and not always aesthetically pleasing results). As soon as I found I was BRCA-neg., we proceeded with radiation. My insurer tried to deny coverage--until my doctors pointed out my ethnicity and diagnosis. Most recent EOB: zero balance.
So, much genetic-mutation testing IS helpful for both prevention and treatment decisions. Don’t throw the baby out with the bathwater!
So, much genetic-mutation testing IS helpful for both prevention and treatment decisions. Don’t throw the baby out with the bathwater!
1
As a breast surgical oncologist one of my missions is to educate leading breast cancer surgeons about advances in care. Our expanding ability to detect harmful mutations is one such advance. But doctors must keep up with all advances in their specific field. Genetics is no exception. The fundamental error in this woman's care was made by the first doctor and perpetuated by the others. A VUS (variant of unknown significance) has absolutely no meaning whatsoever in the clinical setting for a single patient. A patient with a VUS must be told there is literally no useful information there and the test is considered negative for harmful mutations. Ultimately VUS's get reclassified as harmful or not. The vast majority are not harmful. A VUS should never be treated as a possible explanation for anything in the clinical setting. The patient should be managed based on her clinical and family history. Physicians are not the only ones who make this fundamental mistake with VUS's. Even certified genetic counselors occasionally succumb to the temptation to treat a VUS as a potential explanation. This harms the patient and must be avoided. The article highlights the urgent need for CME (continuing medical education) as knowledge of genetics and their relationship to disease expands.
67
Thank you for your comment.
I didn't realize that most VUS's were harmless. However, I have an important question. When you say that the vast majority of VUS's are harmless, are you talking about VUS's that are present in women without breast cancer, or ones that are present in women already diagnosed with breast cancer (particularly early breast cancer)? The combination of a VUS *and* early breast cancer should increase the probability that the VUS is harmful.
Also, it will really depend on the type of mutation. Nonsense and frameshift mutations are far more dangerous than missense mutations and inserted/deleted whole codons.
Also, it will really depend on the type of mutation. Nonsense and frameshift mutations are far more dangerous than missense mutations and inserted/deleted whole codons.
What would be important for the public to know is the probability that genetic testing will provide valuable information about breast cancer treatment for an individual patient and her physicians? How often are the results conclusive versus inconclusive? It is important to know whether breast cancer patients should or should not get tested based on overall statistical findings as long as they understand that they might get inconclusive results that means that the standard treatment decisions apply.
I was diagnosed with breast cancer three weeks ago. It was not a shocking diagnosis given my family history of the disease and my family members' genetic testing. I am going to submit to genetic testing before I make my treatment decisions.
If find the majority of these paranoid comments mystifying.
If find the majority of these paranoid comments mystifying.
19
I too have been in a similar situation and it makes sense under your circumstances to have genetic testing before any further treatment.
4
I was diagnosed with very aggressive breast cancer eleven years ago, when I was 35. Please ignore the paranoia and head-in-the-sand comments on this article. Genetic testing has been incredibly valuable for me. I wish you the best of luck with treatment.
1
I wish you luck with what lies ahead. Absolutely have the testing done so that you know whether you have the BRCA mutation or not. The treatments developed for that particular type of breast cancer are fairly black and white at this time.
The problem is that we are making an educated GUESS when it comes to the treatment of breast cancer. The decisions you have before you have to be the ones that are best for YOU , that give YOU peace, and that YOU can feel confident in making.
The problem is that we are making an educated GUESS when it comes to the treatment of breast cancer. The decisions you have before you have to be the ones that are best for YOU , that give YOU peace, and that YOU can feel confident in making.
I have recently finished Breast Cancer treatment and my genetic testing played a key role in the type of treatment I received. My host of doctors had their act together. I carry the ATM mutation, BRCA2 and an unknown mutation. Based on the ATM diagnoses, we elected to not do radiation because it raised my rate of recurrence to 90%. I also without any prompting elected to have a bilateral mastectomy. My doctors did a magnificent job. I can attest to the fact that genetic testing used wisely is invaluable. Because I was diagnosed, my whole family will be tested to save many future generations from a host of cancers through regular screening and intervention if necessary. Genetic testing worked for me. I encourage it for all patients diagnosed with Cancer. This testing may be the means to finally cure cancers and to answer questions about a families propensity to get cancer. Genetic testing saved me and my family.
26
RML,
I'm happy all worked out for you. Can you explain if it's only the ATM mutation that increases recurrence risk with radiation? How much documentation is there on this? Is this the same for women with BrCa one and two mutations? Thank you.
I'm happy all worked out for you. Can you explain if it's only the ATM mutation that increases recurrence risk with radiation? How much documentation is there on this? Is this the same for women with BrCa one and two mutations? Thank you.
I had a mastectomy for breast cancer, with chemo and radiation therapy. The doctors were ambivalent about the need for radiation, but we all didn't see the harm. Now, a few years later, I've gotten genetic testing, and I, too, have an ATM gene mutation. Had I known, I would have opted out of radiation therapy, knowing it increased my chances of recurrence.
The ATM mutation I have also elevates my chance of pancreatic cancer, which is also in my family. But there's no agreed protocol as to monitoring. But I choose to monitor, since the benefits of early detection far outweigh the lack of consensus.
So, confusing, yes. But I also now feel empowered with at least some knowledge.
The ATM mutation I have also elevates my chance of pancreatic cancer, which is also in my family. But there's no agreed protocol as to monitoring. But I choose to monitor, since the benefits of early detection far outweigh the lack of consensus.
So, confusing, yes. But I also now feel empowered with at least some knowledge.
@ RML - RML you provide a useful example and a happy ending with due praise for the "host of doctors" and for the genetic analyses. I assume therefore that you have excellent medical insurance that made all this possible. I note this because Gina Kolata has provided numerous such stories over the past year or two in which she sometimes points to the teamwork that is involved, teamwork that is costly. What is lacking as I note in my comment URL below is the absence of any information on the cost of the kind of care you have received. In a country - the USA - without Universal Health Care not everyone can be provided what you fortunately were able to be provided.
My comment points to the Public Health Care dimensions of this story:
http://www.nytimes.com/2016/03/12/health/breast-cancer-brca-genetic-test...
Only-NeverInSweden.blogspot.com
Dual citizen USA-SE
My comment points to the Public Health Care dimensions of this story:
http://www.nytimes.com/2016/03/12/health/breast-cancer-brca-genetic-test...
Only-NeverInSweden.blogspot.com
Dual citizen USA-SE
All I can think of is how much farther ahead we'd all be against breast cancer if Komen had spent less money on high salaries for their leadership and travel and advertising and more on actual research.
I'm so glad they were exposed.
I'm so glad they were exposed.
46
All I can think of is how much farther ahead we'd all be against breast cancer if Komen had not bowed to the anti-abortionists movement in 2010, when they removed their funding from Planned Parenthood, which provided mammograms for millions of poor women.
I'm so glad that their true "conservative" identity was revealed.
I'm so glad that their true "conservative" identity was revealed.
14
I'm glad they were exposed too but I don't know if throwing more money at the problem is the solution.
1
I agree and disagree. I agree in that Komen, as an organization, is basically useless. So little of their money goes toward funding research into metastatic breast cancer research (something like 7%, at most) that I've long stopped taking Komen seriously. All the pink parades in the world aren't going to cure breast cancer.
I disagree (though I fully support Planned Parenthood) in that mammograms have now been categorically shown not to reduce the number of breast cancer deaths a year. On the contrary, all those early mammograms lead to unnecessary treatment that comes with more risks than benefits.
I disagree (though I fully support Planned Parenthood) in that mammograms have now been categorically shown not to reduce the number of breast cancer deaths a year. On the contrary, all those early mammograms lead to unnecessary treatment that comes with more risks than benefits.
2
I think it makes far more sense, if one decides to be genetically tested, to do so before surgery.If Ms. Watts opted for a double mastectomy, the lumpectomy would have been for naught. Had I been aware of the depth of my hidden paternal family history when I was initially diagnosed with breast cancer, I most certainly would have tested then and not gone through radiation and lumpectomy. When I did test positively for BrCa 1 4 years later, my risk of recurrence was put at 65%. I couldn't wait to have my ticking time bombs removed and reconstructed. 16 years later, I have never regretted that for a moment. Emotionally, I would have not been a good candidate for nerve wracking surveillance, The statistics are much less grey for the more well known BrCa 1 and 2 mutations. Inevitably, new mutations effecting high risk families would be uncovered. The challenge is that there is not enough statistical data to help guide patients on what to do once they have this new found info. Not easy for those whose path is not as black and white as mine was.
17
I agree with you. With lumpectomy radiation is typically required. That is often not the case with mastectomy. Thus having the genetic testing prior to any surgery and treatment could help avoid radiation treatment in this case.
6
Thanks for sharing your experience. It's useful to know these things for the future. My mom had another kind of cancer, but it was completely mishandled by her doctors. If I knew then what I know now, I would do a lot of things differently.
Seems, like in many medical matters today, that information has gotten ahead of treatment. Information is easy, treatment not. Seeking information is very important, but all to often doctor's do not inform patients of the gulf between information and treatment. Sure, medical technology is advancing at speeds far from what we can use the data for. the quest for 'big data' feeds itself. Think about it, the doctor will know everything about you, yet not be able to 'treat you'. Your on your own.
5
In a way, it seems as if gene sequencing is still at the stage cartography was in Columbus's time. Amazing for the era, but still not too sure where the monsters be.
Since there are some times in treating a cancer that looking for a specific mutation can guide treatment, tests are pretty smart and can aid treatment. But if the results are not well known or understood, we should treat them like the monsters at the edge of the world, and steer clear until we know more. Trying to change treatment based on changes to DNA that we have no idea of how they alter our proteins and the cell function is just crazy. I'd pretend the data doesn't exist and go with best practices.
Meanwhile, we can use all those smart data bases we are supposed to be building to look for trends, identify those sea monsters. And maybe that will give us a better map in the future.
Since there are some times in treating a cancer that looking for a specific mutation can guide treatment, tests are pretty smart and can aid treatment. But if the results are not well known or understood, we should treat them like the monsters at the edge of the world, and steer clear until we know more. Trying to change treatment based on changes to DNA that we have no idea of how they alter our proteins and the cell function is just crazy. I'd pretend the data doesn't exist and go with best practices.
Meanwhile, we can use all those smart data bases we are supposed to be building to look for trends, identify those sea monsters. And maybe that will give us a better map in the future.
22
I am so untrusting of the profit motives of the medical industry that I have, so far, never gotten involved in any sort of screenings or blood testing for any diseases. I try to take care of myself properly and I pay attention to how I feel. I just feel safer going it alone for the time being. The thought of having to figure out whether a doctor can be trusted to do what is right for me vs what he must produce for the practice or hospital that employs him seems too daunting. Friends my age that see doctors regularly are all on multiple prescriptions and go to constant appointments for follow up. I seem healthier than them all. I may very well be very wrong about this but for now, I feel safer staying away.
45
That is sad. It indicates the lack of trust that has occurred between doctors and their patients. The terms "profit motive" and "medical industry" are indicative. When my grandfather practiced medicine in the 1920s and 30s, no patient would ever think about suing a doctor for malpractice. A doctor was like a minister, priest, or rabbi--someone you went to for counseling and advice on sickness and life's ultimate values. Today, doctors are much more knowledgeable about anatomy, physiology, and pathology and have access to a world of new diagnostic technologies and life-saving drugs.
But they have less time to see patients, and avoid primary-care medicine in favor of specialties like radiology and surgery whose procedures they can schedule and are also much better-paying.
But they have less time to see patients, and avoid primary-care medicine in favor of specialties like radiology and surgery whose procedures they can schedule and are also much better-paying.
3
I also mistrust the medical community and have never been tested for anything not a presenting issue, because though there are countless good physicians, the bad apple shills of the pharmaceutical industry have cause me to mistrust them all, and wonder whether even the most ethical of practitioners is needlessly prescribing.
Are you untrustworthy of the profit motive of all industries or is there something specific about the profit motives of the medical industry that particularly gets your goat?
It seems that Ms Watts's oncologist could make a rough calculation to determine the probability that radiation treatment might cause further damage to the particular gene. If the probability were 5 per cent or less, it would be rational to go forward with the treatment.
In any case, doctors would be wise to heed the advice of Hippocrates, the father of medicine: Do No Harm.
In any case, doctors would be wise to heed the advice of Hippocrates, the father of medicine: Do No Harm.
4
This article is exactly why I refused additional genetic testing 8 years after my breast cancer diagnosis. I was negative for BRCA1 and 2. "But they've made so many advances in genetic testing," the doctor said. But there was nothing that would change about how I live my life now - I get regular screening, I eat healthy, exercise, reduce alcohol and try to keep my weight down. If there is nothing more to be done, I don't want the test.
18
Well the message seems to be that genetic testing is only helpful if it leads to successful treatment/"a cure". This article reflects the shortsighted American propensity for valuing info which will cause one to live longgggg but not info that will help one die well. As a Stage 3 breast cancer patient with not great pathology stats and hanging on the precipice of Stage 4, I want Truth to help me plan and prepare.....whether the testing evokes my longstanding magical god/western medicine thinking or whether it pushes me into the uncomfortable but valuable reality that I'm headed for a very BIG storm and need to prepare personally and appropriately. How dare doctors imply that testing is "stressful" or "useless" just because they don't know how to use it to cure patients! How dare insinuate that women won't be able to deal with real info and make appropriate decisions, however difficult!
25
I agree. As someone with Stage IV breast cancer, who has lived with Stage IV cancer for almost six years, I am not dead yet and am living very well. If I hadn't had testing after being remission for over three years, because I had a hunch that something was wrong, my metastasis would not have been found when it was, and I could very well have died by now. Patients have a right to know about their own health. We don't need doctors to protect us.
2
I'm afraid this is only the start of things. While "personalized medicine" is a terrific goal, we are far from that holy grail. Meanwhile, the price of genetic tests, screening and even sequencing entire genomes are rapidly falling. Companies like 23andme are already on that road.
There will be a period of large data sets and a lot of confusion as patients learn of their quantitative risks and probabilities of several diseases, not just cancer. And just like this article, it will be quite unclear what to do if you have a X% chance of getting disease Y.
There will be a period of large data sets and a lot of confusion as patients learn of their quantitative risks and probabilities of several diseases, not just cancer. And just like this article, it will be quite unclear what to do if you have a X% chance of getting disease Y.
4
Here's the next step in research in this area.
Survey all doctors, including all oncologists and all other specialists. Ask them two questions: (1) are they willing to take genetic tests for all presently known possible life threatening conditions? (2) What will they do in the light of ambiguous results for them and no confidence in there being any effective treatment?
Publish the results.
Survey all doctors, including all oncologists and all other specialists. Ask them two questions: (1) are they willing to take genetic tests for all presently known possible life threatening conditions? (2) What will they do in the light of ambiguous results for them and no confidence in there being any effective treatment?
Publish the results.
16
I have a family history of breast cancer. My doctors tried for years to get me to do genetic testing, and three years ago I finally did. Even knowing I was at higher risk already, I was devastated to learn that I had the BRCA2 mutation.
Now I wish I'd never had it done. It caused me a lot of stress, and ultimately I decided to do what I'd been doing all long -- have regular screening and check-ups, eat well, exercise, laugh with family and friends, and try to be happy.
I'm not at all diminishing the horror of this illness; I've seen it first-hand. But I think this all involves a most personal choice.
I just wish I'd thought about what I'd do with the knowledge -- prophylactic surgery or nothing -- before having the testing done.
Now I wish I'd never had it done. It caused me a lot of stress, and ultimately I decided to do what I'd been doing all long -- have regular screening and check-ups, eat well, exercise, laugh with family and friends, and try to be happy.
I'm not at all diminishing the horror of this illness; I've seen it first-hand. But I think this all involves a most personal choice.
I just wish I'd thought about what I'd do with the knowledge -- prophylactic surgery or nothing -- before having the testing done.
20
I hope you at least are having your fallopian tubes removed (tremendous reduction in your very high ovarian cancer risk with relatively minimal surgery/ after effects) and having yearly breast MRI and mammogram (early detection = very likely cure).
You did the right thing. You are in control.
You did the right thing. You are in control.
2
Like you my closest friend had a family history of breast cancer but no one had died of it so she reasoned if she got it she also would survive. I begged her to get tested even offered to pay as then she could make an informed choice . Unfortunately she choose to wait and died at age 38 leaving two small children.
Knowledge is power. Always!
Knowledge is power. Always!
7
I deeply sympathize with your situation. That's the problem with a lot of "care" givers: they want to throw everything they have at you, and in many cases it's misguided, counterproductive, poorly thought through, or just plain wrong. Peace of mind is a wonderful thing, and when they rob you of that, even though you live on, something very, very valuable has been taken from you. All too many doctors don't understand that.
All best wishes to you for a long life of good health.
All best wishes to you for a long life of good health.
1
For me, medical information is power to make rational decisions when facing serious illness, but this is a story where the patient is left in a much worse emotional state following genetic data about her breast cancer. In the process of providing the best possible medical care, a very unfortunate error was made. Patients should be screened by appropriate mental health specialists to determine whether ambiguous genetic information will serve to improve or diminish patient outcomes. In the case of cancer, many doctors know that a positive outlook can result in better outcomes than established treatments.
2
It is a self-destructive act, in my opinion, to get tested for a deadly disease that has no effective cure. What's the point other than to financially reward Big Pharma ?
Genetic testing done willy-nilly, with no thought given to how tests negatively impact a patient's mental health, is simply bad medicine.
Genetic testing done willy-nilly, with no thought given to how tests negatively impact a patient's mental health, is simply bad medicine.
50
I disagree. Even when there is no known effective treatment, it is important to know as much about a disease as possible; and cancer is a perfect example. Maybe the information will not directly help the afflicted patient. But over time the gathering of information, retrospective studies of treatment outcomes, future incites and discoveries, may indicate a pattern which will lead to a greater understanding of the disease and eventually to effective treatments. The bottom line is that you will never know what information is important if you don't gather the information.
2
Perhaps you are healthy. For those of us who have had or have cancer, we don't blithely generalize about "Big Pharma." Our doctors are not out to kill us or make money on us. My doctors are trying to cure me. They don't make "willy-nilly" choices. Any doctor who does is not a good doctor. Fortunately, there are enough good doctors out there who actually do care.
2
Yet if they are able to track genetic mutations with treatment plan and outcomes, that will still advance the science, helping other patients down the road.
I propose the treatment for breast cancer shouldn't be a financial burden to women since we all have mothers, many have sisters, wife and daughters. The optimal and best treatment for breast cancer should be based on research, randomized clinical trials and financial ( direct or indirect) incentives for treatment providers should be off the table.
6
th downside of modern medicine is that it has given us th vague feeling that it can cure everything and we will live forever
since we all will die at some point, th best course to take is to enjoy, or to at least experience, th moments available to us, and not fritter what time we do have in worry about th future
bc it is but a moment, then an eternity of nothingness
since we all will die at some point, th best course to take is to enjoy, or to at least experience, th moments available to us, and not fritter what time we do have in worry about th future
bc it is but a moment, then an eternity of nothingness
5
No news is good news, aka TMI. Careful with a doc who gives out questionable betting data, then advises not to bet, which, by his definition, a double-M. Bordering on unethical, delivering this kind of traumatic "advice".
Whew, what a close shave! Very happy to hear Ms. Watts chose not to go the way of Ms. Jolie. But she should still write about it in the NYT.
Whew, what a close shave! Very happy to hear Ms. Watts chose not to go the way of Ms. Jolie. But she should still write about it in the NYT.
4
Angelina Jolie was smart. And she didn't remove her breasts in order to become more famous but in order to live. What a cynical idea. As someone who has had aggressive breast cancer, I would have loved to have removed my breasts before getting a potentially fatal disease.
@AKS
Think so huh? She made a double M decision based on statistics alone. That's it. No symptoms, no lump, no nuthin'. Then she wrote about it hoping to play role model. Excuse me? You wanna role model, write this story. Instead of how you gave in to docs eager to chop breasts on the basis of statistics alone.
Jolie should be suing them for malpractice. Or working on a college degree or something. Not writing a tear-jerky in the NYT about how doctors eager for breasts managed to scare her using dodgy statistical science. Those guys are being not just voyeuristic but also opportunistic-predatory. Here we are shocked at Gawker and Hulk Hogan. Well, guess what, there are doctors out there worse than the two combined. How do they even keep their licenses? Maybe Ms. Watts will explore that question next.
Think so huh? She made a double M decision based on statistics alone. That's it. No symptoms, no lump, no nuthin'. Then she wrote about it hoping to play role model. Excuse me? You wanna role model, write this story. Instead of how you gave in to docs eager to chop breasts on the basis of statistics alone.
Jolie should be suing them for malpractice. Or working on a college degree or something. Not writing a tear-jerky in the NYT about how doctors eager for breasts managed to scare her using dodgy statistical science. Those guys are being not just voyeuristic but also opportunistic-predatory. Here we are shocked at Gawker and Hulk Hogan. Well, guess what, there are doctors out there worse than the two combined. How do they even keep their licenses? Maybe Ms. Watts will explore that question next.
1
"A genetic test showed she had inherited an alteration in a gene needed to repair DNA."
This would have been a better article if the gene was mentioned, whether it's specific function is required for repair of double strand breaks, and whether Ms. Watts was a carrier for the mutation or her cells were deficient for the enzyme. I realize that these things can get complicated, but Ms. Kolata is a very experienced science writer and could easily deal with presenting technical issues for the public. As written, however, the article presents the problem without really detailing why the doctors gave conflicting opinions or why Ms. Watts made the decision she did.
This would have been a better article if the gene was mentioned, whether it's specific function is required for repair of double strand breaks, and whether Ms. Watts was a carrier for the mutation or her cells were deficient for the enzyme. I realize that these things can get complicated, but Ms. Kolata is a very experienced science writer and could easily deal with presenting technical issues for the public. As written, however, the article presents the problem without really detailing why the doctors gave conflicting opinions or why Ms. Watts made the decision she did.
6
It was a mutation. Patient was given a little more information about the mutation. And from that The patient was able to make a decision... Patient has two science degrees... That helps the patient understand the consequences...
Most likely this is a BRCA gene alteration. It is not a "mutation" but rather a variation of unknown significance. Some variations are known to be harmful, some are not and for these others, the companies will update you as they see enough of these variants to determine if they are harmful. As a breast cancer surgeon, I don't recommend acting on these variations as the vast majority end up not being harmful. Whenever possible, genetic testing should be done by genetic counselors who can help patients understand these possibilities, talk to them on how they will feel about the results and help guide them into figuring out if the testing makes sense for each individual.
1
It's possible that Ms. Watts doesn't want her particular mutation/gene combination mentioned. For now, that data likely wouldn't harm her ability to get insurance (not just health insurance but life and disability insurance) because variants of unknown significance are often later determined to be benign. However, evidence may later support a deleterious role for Ms. Watts mutation. Having it freely available to the public might not be in her best interest.
As for what mutation it was, I would hazard a guess that it very well could be a VUS in BRCA1 or BRCA2. There are over 1700 unique mutations that have been reported in BRCA1, but only 800 of those have known clinical significance. The rest are either variants of unknown significance or variants that have been determined to be benign. (Source: http://research.nhgri.nih.gov/bic/). Likewise, there's about 2000 unique germline mutations described in BRCA2. That data repository gives the level of evidence for each mutation in a 5 class system.
Both genes are involved in a type of DNA repair called homologous recombination. Further, there are a few other DNA repair genes that are less commonly mutated in hereditary breast cancer, including PALB2, CHEK1 and CHEK2, and ATM. There are clinical trials available for patients with mutations in these genes, but they often require knowledge the mutation is deleterious.
Like you, I found this article lacking for several reasons, which there isn't room to detail in 1500 characters.
As for what mutation it was, I would hazard a guess that it very well could be a VUS in BRCA1 or BRCA2. There are over 1700 unique mutations that have been reported in BRCA1, but only 800 of those have known clinical significance. The rest are either variants of unknown significance or variants that have been determined to be benign. (Source: http://research.nhgri.nih.gov/bic/). Likewise, there's about 2000 unique germline mutations described in BRCA2. That data repository gives the level of evidence for each mutation in a 5 class system.
Both genes are involved in a type of DNA repair called homologous recombination. Further, there are a few other DNA repair genes that are less commonly mutated in hereditary breast cancer, including PALB2, CHEK1 and CHEK2, and ATM. There are clinical trials available for patients with mutations in these genes, but they often require knowledge the mutation is deleterious.
Like you, I found this article lacking for several reasons, which there isn't room to detail in 1500 characters.
1
I was talked into having genetic testing. I initially demurred because I didn't think my insurance would pay. Oh they'll pay I was told. I asked that they check. They called me had told me they checked and and my insurance would pay. As I was signing paperwork, I was told, don't worry you would never have to pay more than $100 or $200 (I'm thinking copay).
Well, I get a letter from my insurance company informing me they had asked my radiologist for more information to justify the genetic testing. I hear nothing for a while and then get a letter of denial and information about how to dispute the denial.
My insurance company was billed in excess of $4,000.
Now who's gonna pay?
Well, I get a letter from my insurance company informing me they had asked my radiologist for more information to justify the genetic testing. I hear nothing for a while and then get a letter of denial and information about how to dispute the denial.
My insurance company was billed in excess of $4,000.
Now who's gonna pay?
40
Been there. You risk getting into a sort of billing version of the old computer game Pong whenever you dispute a coverage denial. I've been told by my insurer to have the medical provider review the coding and resubmit the charge, only to be denied again, and then be told to do the same thing again, and again. Eventually it all gets delayed long enough that it goes to collections and you have to pay and hope to be reimbursed. But you won't be. So the best advice I can give is to negotiate with the billing office for a reduced charge. They generally can and will reduce it. Medical providers are usually settling for a contracted, reduced rate from the insurance company anyway.
7
Primary care doctors recommend specialists for everything which can increase a patient's stress level. Because my mother died from ovarian cancer and had breast cancer he wanted me to do genetic testing. My mother didn't have the Brac genes and figured I wouldn't either but went ahead with the testing...one thing I learned was not all insurances will pay for it. Mine did luckily and the genetic counselor shopped around for the best priced lab for testing. As I thought - I didn't have the gene mutation but the test found a gastric related mutation that was as of yet unclear. Counselor was not concerned but primary care doctor had me go to a specialist to do the EGD just to make sure. Specialist was surprised but we went ahead with the test and he did find a minor gastric inflammation. Rather than take a prescription from my doctor opted to go with a naturopath first. Least invasive is best - surgery should not be the first option, There were times I wished I didn't do genetic testing - yet with a good counselor and doctor (albeit test happy) it can help but the patient has to be level headed otherwise you will flip out, I almost did.
8
I'll be frank genetic testing is a boon for companies that do genetic testing but not for patients. That is why it was included. Genes are only a marker. This president and this congress won't do anything about cancer causing agents in our water, our air or our food! Why because the corporations don't want it. But testing is a gold mine.
64
That is a pretty cynical statement. I criticize Obama for many things, mostly those that feed our malignant and metastasizing bureaucracy, but not for that.
5
This President has tried quite hard to increase the role of the EPA and the FDA in monitoring and improving the quality of our air, food and water. By contrast, we have a Congress with its head stuck in the sand who would rather do nothing that might incur the wrath or the Tea Party True Believers.
4
It is kind of hard to do anything about all those cancer causing agents when the vast majority of them are naturally occurring. Hate to say it but nature is really good at producing poisons. Plants are especially good at it as they need a way to defend themselves from everything trying to eat them and the can't run away. As your cells burn fuel they create their own waste products that are poisons to the cell itself and may cause genetic mutations within the cell that may lead to cancer. The only way to make your cancer risk zero is to stop all cell metabolism. You have to die for that to happen.
It's all theoretical if your insurance company won't pay for timely "diagnostic" services, even when you're paying 15% of your salary for said insurance.
12
We are in an extensive information gathering phase. Although it may be stressful right now to find information and not being able to interpret it, ultimately this info will be integrated and serve to establish better treatments.
As for the physician's response is concerned: They are caught between a rock and a hard place. If they do not proceed with the most aggressive or advanced treatment they risk being sued. That more than anything drives our health care costs.
As for the physician's response is concerned: They are caught between a rock and a hard place. If they do not proceed with the most aggressive or advanced treatment they risk being sued. That more than anything drives our health care costs.
5
As horrible as Angie Watts's conundrum was -- I am sorry she had to go through that -- what I thought when I read this is at least she got advice. It may have been conflicting and confusing advice, but at least informed, honest and sincere options were were given. When tests revealed that I had an uncountable number of uterine fibroids -- a riotous mass of lumpy tissue that was causing pain and could possibly become cancerous in future -- I was told (coldly) that the masses were too many for excision, and that my options were either a hysterectomy or wait-and-see. The gynecologist refused to voice her opinion about what I should do. My primary care physician, when asked, would not even talk about it (no billing code for that). Are physicians so afraid of liability that they won't risk taking an active part in choosing among a patient's treatment choices? Or is it strictly a billing, timekeeping, profitability constraint? I was floored that no one would help me decide. I thought that sort to thing was part of the whole "first, do no harm" oath. You don't give a patient bad news and then say, "do with that what you will."
23
It's all liability. We can thank the lawyers for that.
Medicine remains an art, not an exact science. Nevertheless, if the outcome does not fit the patient's expectations, we get sued. Then it is a matter of which lawyer can extract more sympathy from the jury, which is usually composed of non-medical lay people. The risks are just too high, the physician is better off not saying anything. Reduces the risk. Just what you experienced.
There was a time when things were different and medicine was rewarding to practice. Not so much anymore. Patient care has become cold and technical and the patient is often left alone with the worry and confusion.
I sympathize with you!
Medicine remains an art, not an exact science. Nevertheless, if the outcome does not fit the patient's expectations, we get sued. Then it is a matter of which lawyer can extract more sympathy from the jury, which is usually composed of non-medical lay people. The risks are just too high, the physician is better off not saying anything. Reduces the risk. Just what you experienced.
There was a time when things were different and medicine was rewarding to practice. Not so much anymore. Patient care has become cold and technical and the patient is often left alone with the worry and confusion.
I sympathize with you!
Don't blame the attorneys, blame the multi-national insurance corporations who care only for numbers and profit, profit from delay, profit from extensive, unnecessary testing.
2
Really, decisions should be made ONLY on the basis of controled studies. The lack of such studies - mainly because every patient demands cutting edge, proven or not- is a national disgrace and is bankrupting the country. Results of unknown significance should NOT be available for patient care and speculation but should be subjected to statistical evaluation for future patients.
4
By necessity, the large, randomized controlled studies are giving way to n=1 and basket studies in rare diseases and cancer. We are increasingly realizing that every patient is an n of 1. As long as the "trial" is based on a solid rational basis and the outcome is interpretable one way or the other, these studies can be extremely valuable.
A good example are EGFR tyrosine kinase inhibitors. Gefitinib was not successful in a large randomized lung cancer trial, where its benefical effect did not reach significance, but only because less than 10% of the patients had the molecular mutation that made it effective. However, for that small percentage, the effect was huge.
It all depends on study design and patient selection and in rare diseases and cancer, that can mean very small groups.
A good example are EGFR tyrosine kinase inhibitors. Gefitinib was not successful in a large randomized lung cancer trial, where its benefical effect did not reach significance, but only because less than 10% of the patients had the molecular mutation that made it effective. However, for that small percentage, the effect was huge.
It all depends on study design and patient selection and in rare diseases and cancer, that can mean very small groups.
15
Why isn't Ms. Watts' genetic mutation identified in the article? Was it a p53 mutation (Li Fraumeni Syndrome)? As someone who was recently diagnosed with LFS, I would be interested in knowing whether her mutation of unknown significance was related to this or another type of genetic mutation.
3
Variant of unknown significance in the ATM1 gene....
3
Variant of Unknown Significance... In the ATM1 gene
If I had to guess, I would say she most likely has a BRCA1 or BRCA2 alteration but, as the article points out, a variant of unknown significance.....
Personalized or precision medicine: autologous T-cell immunotherapy is on this path to cures. The business model for them is not necessarily big pharma blockbuster drugs. (We're, also, waiting for Watson to get it all together.)
In China they have a word for over diagnosis: "Doctor Patient Disease." Genetic testing give some doctors license to exercise their overly determinist mind. That is actually anti-scientific thinking and leaves out a respectful humility in the face of biological complexity. In the past we would call it "playing God," now it's more liable to fall under such rubrics as "patriarchy," "egotism" or "erring on the side of prudence." All of those are subset of the Protestant emphasis on text, kinda like Scalia on the Constitution. We all need to be more comfortable with the "Cloud of Unknowing" especially when it comes to life and death health choices.
10
10% of doctors put YOU first. 90% are fretting about paying for their beach home and Jaguar. Sorry, but true. Most Oncologists will treat you long after you are dead, for the money. They want you to "battle" cancer, long after it doesn't make any sense. For True.
55
What a ridiculous over generalization of doctors
46
More likely, if they are employed by a medical group, fretting about complying with the billing and timekeeping rules imposed by their employer.
6
That's a gross exaggeration. I am sure it is true of a some minority of doctors, but most oncologists I have met are fine and very ethical doctors. That doctors disagree is not a sign they are trying to take advantage of you, or dupe you for money.
If anything, I have found that doctors are quite removed from the financial side of things -- they have billing people for that -- they don't even know what they charge most of the time, or what the surgery or medications they prescribe will cost you.
My dad was diagnosed in 2002 with Stage 4 metastatic colon cancer. His oncologist told him that he could do chemo and radiation, and it might prolong his life by a year or two if he was very lucky -- but much of that time, he would be dreadfully weak and sick due to the treatment. And that if the doctor were in my dad's place, he'd take the time he had -- 3-4 months they said -- and spend it reasonable comfort with family and friends, putting his affairs in order.
And that's what he did. After initial depression at his diagnoses, he came to a sense of peace & acceptance, and actually lived another 22 months (instead of 3).
But in no way did his doctors pressure him to have treatment he didn't want. And dad was 77 and on Medicare, they could have pushed him into any sort of costly treatment.
If anything, I have found that doctors are quite removed from the financial side of things -- they have billing people for that -- they don't even know what they charge most of the time, or what the surgery or medications they prescribe will cost you.
My dad was diagnosed in 2002 with Stage 4 metastatic colon cancer. His oncologist told him that he could do chemo and radiation, and it might prolong his life by a year or two if he was very lucky -- but much of that time, he would be dreadfully weak and sick due to the treatment. And that if the doctor were in my dad's place, he'd take the time he had -- 3-4 months they said -- and spend it reasonable comfort with family and friends, putting his affairs in order.
And that's what he did. After initial depression at his diagnoses, he came to a sense of peace & acceptance, and actually lived another 22 months (instead of 3).
But in no way did his doctors pressure him to have treatment he didn't want. And dad was 77 and on Medicare, they could have pushed him into any sort of costly treatment.
62
History will not be kind to any entity that was connected to breast cancer screening or treatment. What the marketing within the medical-industrial complex has hoodwinked women into believing is a sham of Biblical proportions. Women who have done as they are told, genetic screenings, mammograms, surgery and chemotherapy, convinced that this baloney actually saved their lives, instead of turning their worlds and that of their family's upside-down, is a human tragedy akin to any in history. And yet, paradoxically, the marchers continue with their pink ribbons, as if marching will validate their decisions. It is a story worthy of Edgar Allen Poe.
I've been in healthcare for 40 years, mixing the noxious chemotherapy that destroys more than it helps. My wages are nothing more than blood money. For that, I am certain there will be a reckoning.
I've been in healthcare for 40 years, mixing the noxious chemotherapy that destroys more than it helps. My wages are nothing more than blood money. For that, I am certain there will be a reckoning.
30
So, you are saying all the effort on breast cancer has not meaningfully increase survival, downstages the average presentation, or improved patient care? I doubt you are actually in medicine or, if you are, your only job is "mixing chemotherapy".
7
So, you are saying all the effort on breast cancer has not meaningfully increase survival, downstages the average presentation, or improved patient care? I doubt you are actually in medicine or, if you are, your only job is "mixing chemotherapy".
Yes. That is exactly what I'm saying. Many, many women, who are never screened, live long and happy lives with breast cancer. In fact, most die of something else.
Remember, it is one thing the have cancer; quite another to know you have cancer. Questioning my credentials is just a form of rationalization.
Yes. That is exactly what I'm saying. Many, many women, who are never screened, live long and happy lives with breast cancer. In fact, most die of something else.
Remember, it is one thing the have cancer; quite another to know you have cancer. Questioning my credentials is just a form of rationalization.
2
Breast cancer deaths have declined by about a third over the past 20 years. See figure 2: http://www.cancer.org/acs/groups/content/@research/documents/document/ac...
I absolutely question your credentials.
I absolutely question your credentials.
8
We are at the very forefront of genetic-based medicine. It takes time to develop treatment that targets genetic mutation. But the scientific community is discovering new mutations and their roles in disease all the time. I understand it may be cold comfort to someone who is sick now with no readily available treatment option, but all of the data collected from patients now can help develop our knowledge of the role of mutations going forward.
9
The allure of genetic testing is very strong, and in many instances a reasonable, appropriate and even necessary thing to do. However, a good rule to follow would be that if the meaning of a test result isn't known, or if a test result isn't going to change the course of therapy, then the test should probably not be ordered or performed.
13
There has always been uncertainty in medicine; physicians often say that medicine is more an art than a science, another way of stating that available medical knowledge often does not provide clear-cut answers.
In decades past, this was often hidden from patients by their Marcus Welby-esque phyisicians, who would apply their scientific knowledge, experience, and gut instinct to guide treatment of disease. Today, many patients wish to assume more control, and make their own determinations. This is a good thing, but it means the weight of life-altering decisions, often based on too little hard information, must now be borne by patients and parents, and it is daunting. Welcome to the world of medicine. Too many test results and too little guidance about what the results mean inevitably provokes anxiety.
Things are getting better; we are continuously learning more about what the various genetic results mean, and how they should guide therapy. Every day, precision medicine improves medical decision making, and improves the odds that a chosen drug will be effective.
But there will always be uncertainty about the choice of therapy, or whether to treat at all. Sometimes it’s better to allow a disease, even some cancers, to run their course, wherever this may lead. Fortunately, as medical science advances, we’re getting better at making therapeutic decisions. There will more correct choices made, but there will always be some wrong ones as well.
In decades past, this was often hidden from patients by their Marcus Welby-esque phyisicians, who would apply their scientific knowledge, experience, and gut instinct to guide treatment of disease. Today, many patients wish to assume more control, and make their own determinations. This is a good thing, but it means the weight of life-altering decisions, often based on too little hard information, must now be borne by patients and parents, and it is daunting. Welcome to the world of medicine. Too many test results and too little guidance about what the results mean inevitably provokes anxiety.
Things are getting better; we are continuously learning more about what the various genetic results mean, and how they should guide therapy. Every day, precision medicine improves medical decision making, and improves the odds that a chosen drug will be effective.
But there will always be uncertainty about the choice of therapy, or whether to treat at all. Sometimes it’s better to allow a disease, even some cancers, to run their course, wherever this may lead. Fortunately, as medical science advances, we’re getting better at making therapeutic decisions. There will more correct choices made, but there will always be some wrong ones as well.
5
The cancer establishment has promised more than they can deliver. Patients are the unfortunate victims, caught in the middle of small, unverified pieces of knowledge, with little meaningful guidance on how to optimize their health.
Personalized medicine based on genetic information is a laudable goal, but we have few examples of evidence-based successes. Professionals have not been diligent in self-monitoring what they can really offer versus what they would like to be able to offer.
Patients need to be protected from unfounded claims, and from tests that will only lead to uncertainty in their treatment plan.
Personalized medicine based on genetic information is a laudable goal, but we have few examples of evidence-based successes. Professionals have not been diligent in self-monitoring what they can really offer versus what they would like to be able to offer.
Patients need to be protected from unfounded claims, and from tests that will only lead to uncertainty in their treatment plan.
22
Uncertainty comes from imperfect knowledge, not deception. How does one protect against ambiguity in a developing science? Unfounded claims - pure hucksterism. Ambivalence from incomplete scientific knowledge - part of life.
I was recently diagnosed with stage 1 skin melanoma 0.22 mm on my arm. The dermatologist took a large chuck of flesh from my arm and the biopsy indicated that the cancer was contained to the original biopsy site. He wanted to see me every three months for a year. It's been a year and all is fine. He says 99% chance that cancer will not come back. During my last visit he informed me there was a genetic test available to determine my metastatic risk. I asked him what I would do If I had a high metastatic risk. He said he would refer me to an oncologist - for regular screening and testing. I'm 73 years old. What do you think I decided to do?
47
As a 74 year old, I would say "hopefully nothing".
10
They want the money. Sorry.
3
If it is the Castle Biosciences test that is being offered, then I hope you said no because that test does not accurately predict recurrence for Stage 1 patients. Moreover, if you had a thin Stage 1 melanoma that was full resected you have a 99.9% chance of having been cured by your dermatologist. My advice is to go off and enjoy your life without any worry of a future melanoma recurrence.
6
As with most areas in medicine, whether testing, procedures or medications, the importance of time counseling a patient beforehand is of critical importance. We need to reimburse physicians, nurses, PAs for time spent with patients, not how many clicks and scrolls they can generate on an electronic record. Then , " surprises " and non realistic expectations are reduced. Perhaps the genetic testing should report only mutations that do affect treatment options unless testing is being done in a research setting with detailed informed consent.
33
Unfortunately, even this article by Ms Kolata, is quite naive, in the sense of not being nearly critical enough. The very nature of the evidence needs to be considered more seriously; it is mainly based on various sorts of comparative sampling and statistical assumptions. It is well known by now that, for reasons that are not known, the same identified BRCA mutation can be associated with dramatically different risks, depending on the study population etc.
The idea of 'precision' medicines sounds unique and new but it is mainly a marketing label for establishing big open-ended data bases. All you have to do is ask what 'precision' means, to know that physicians throughout history have always aimed to be as precise and as personalized as they can. To say 'precision genomic' medicine hints at the belief system that genes predict almost everything 'precisely', and for many reasons those in the know, know very well that that is not so.
None of this reduces the challenge, nor does it say that genomic data are useless, but it does argue for greatly toning down the claims, promises, and spin that have become so much a part of genomics. There are many reasons for thinking that what we see (the generally weak predictive power in situations like this) is what we should expect to see.
Science articles in the popular press should start dealing with these deeper issues.
The idea of 'precision' medicines sounds unique and new but it is mainly a marketing label for establishing big open-ended data bases. All you have to do is ask what 'precision' means, to know that physicians throughout history have always aimed to be as precise and as personalized as they can. To say 'precision genomic' medicine hints at the belief system that genes predict almost everything 'precisely', and for many reasons those in the know, know very well that that is not so.
None of this reduces the challenge, nor does it say that genomic data are useless, but it does argue for greatly toning down the claims, promises, and spin that have become so much a part of genomics. There are many reasons for thinking that what we see (the generally weak predictive power in situations like this) is what we should expect to see.
Science articles in the popular press should start dealing with these deeper issues.
15
Steve Jobs imagined a day when a Standford graduate student would use his laptop to cure cancer. So few have accepted this challenge, including oncologists.
Today, there is very little motivation to cure cancer since it's academic suicide due to the high risk. BioPharm has imploded and now waits for the small company to be lucky.
Personalized medicine is a sham if there's no search for therapeutics. This is just NIH Big Science. Next year, there will be a new slogan, a Shot to Mars!
Today, there is very little motivation to cure cancer since it's academic suicide due to the high risk. BioPharm has imploded and now waits for the small company to be lucky.
Personalized medicine is a sham if there's no search for therapeutics. This is just NIH Big Science. Next year, there will be a new slogan, a Shot to Mars!
1
Paul, you speak as if you know little of what you are talking about. You say that, "Today, there is very little motivation to cure cancer since it's academic suicide due to the high risk." Tell that to the tens of thousands of students, fellows and faculty working 12 hour days, six or seven days a week in academic medical centers and research institutes trying to come up with new ways to prevent, diagnose and treat cancer. And as far as a search for therapeutics is concerned, how about Herceptin, Gleevec, Tarceva, Yervoy etc etc etc?
42
I'm sorry, whenever I see these "they don't want to cure cancer" comments, I aways think what an idiotic idea. Don't you realize that "they" - doctors, medical scientists and even Big Pharma workers get cancer too? Wouldn't they like to prevent the deaths of themselves or their loved ones?
30
There is plenty of searching for therapeutics going on. Getting them through the regulatory thicket and being able to pay for the trials is what slows us down more than anything.
This is a great time for medicine and biology. Both feed each other as genome sequencing is getting cheaper and data start pouring in. Personalized medicine is the future.
This is a great time for medicine and biology. Both feed each other as genome sequencing is getting cheaper and data start pouring in. Personalized medicine is the future.
4
What's forgotten, sadly, is that: Science IS NOT Medicine
4
Perhaps some scientists are using women with breast cancer as research tools only????
4
In order to advance our search for cures, everyone is a research tool.
Here's something I don't understand. Whether or not she has a gene which makes her more susceptible to radiation, doesn't radiation treatment increase the probability of getting cancer? My MIL had radiation treatment for breast cancer in her early 30s, which was successful, but she ended up developing lymphoma when she was in her 60s, that may have been related to radiation.
Have there been studies comparing lumpectomy and radiation vs. mastectomy that looked at those patients 25 or 30 years later?
Have there been studies comparing lumpectomy and radiation vs. mastectomy that looked at those patients 25 or 30 years later?
8
DebbieR, you are right: BOTH radiation treatment AND chemotherapy increase risk for leukemia down the road. And the doctors don't seem to talk much about this. Radiation also increases risk for other cancers, including angiosarcoma -- which seems swiftly fatal, from what I've read -- as well as causing many other problems. And it seems as though many, too many patients, are not informed about these risks. Because these treatments involve both possible benefit and possible seriously severe adverse effects, up to and including death, my "gold standards" are now: what is the effect of treatment on overall mortality -- not just the effect of the treatment on dying from a particular cancer -- and what is it's effect on quality of life?
2
Genetic testing for the purpose of "personalizing" drug therapy in cancer is over hyped/under performing. For the overwhelming majority of drugs actually used in to treat most cancers, information provided by genetic testing is virtually useless.
The problem is that cancer drugs have effects on multiple pathways and also that cancer cells can escape drug effects through multiple mechanisms. The drugs have to gain entry into the cancer cells; have to avoid being extruded by the cells; have to avoid being inactivated by the cells.
A far more useful approach -- supported by an abundance of peer review research -- is to perform "culture and sensitivity" tests, analogous to those used in bacterial and other infections. The cancer cells are cultured; drugs are added to the cultures; measurements are made of the degree to which the drugs kill the cancer cells.
Alas, the US National Cancer Institute and academic cancer research community made the command decision in the late 1980s to abandon support for research and clinical trials with these cell culture technologies and erected unprecedented barriers against their utilization. These tests limit the ability of oncologists to choose the most remunerative drug regimens (shown to correlate strongly with drug selection) and limit the the ability of research institutions to steer patients onto clinical trials.
It's the greatest lost opportunity in the history of clinical cancer research.
The problem is that cancer drugs have effects on multiple pathways and also that cancer cells can escape drug effects through multiple mechanisms. The drugs have to gain entry into the cancer cells; have to avoid being extruded by the cells; have to avoid being inactivated by the cells.
A far more useful approach -- supported by an abundance of peer review research -- is to perform "culture and sensitivity" tests, analogous to those used in bacterial and other infections. The cancer cells are cultured; drugs are added to the cultures; measurements are made of the degree to which the drugs kill the cancer cells.
Alas, the US National Cancer Institute and academic cancer research community made the command decision in the late 1980s to abandon support for research and clinical trials with these cell culture technologies and erected unprecedented barriers against their utilization. These tests limit the ability of oncologists to choose the most remunerative drug regimens (shown to correlate strongly with drug selection) and limit the the ability of research institutions to steer patients onto clinical trials.
It's the greatest lost opportunity in the history of clinical cancer research.
24
Maybe, but with most cancer drugs having efficacy comparable to antibiotics in the pre-penicillin era, treatment is still going to fail many patients regardless of how many culture and sensitivity studies are done. It seems to me that if there is limited research funding it should go to novel treatments, not to incremental improvements at the bedside which can be done (and are being done) relatively cheaply at the level of the facility and the treating provider.
To Larry Weisenthal: Do you have any citation for this?
1
The more I observe my reactions to wheat, rye, barley (the triticale family), the more impressed I am that these grains poison us.
2
What on earth does that have to do with this article? Making such suggestions, with no science at all behind it, is just fear mongering and very cruel to people suffering from a deadly disease.
13
I agree that the comment is not directly related but there is growing interest in figuring out which of the foods we eat feed voraciously hungry cancer cells and from what I have read, many cancers grow more rapidly when the diet is high in sugars, which includes most, if not all, grains. There has been some work done exploring the effects of a ketogenic diet on cancer.
1
Funny, I am not at all sensitive to wheat, rye, barley (the triticale family), neither are any of my close or extended family or friends. Hence, I am equally convinced that these grains do nothing of the sort......