Growth factor predicts poor outcome in breast cancer
The response to insulin-like growth factor 1 in breast cancer cells predicts an aggressive tumor that is less likely to respond to treatment, said researchers at Baylor College of Medicine in a report that ...
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Since: Dec 05
#1 Aug 30, 2008
Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for individual patients.
Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeting one pathway may not be as effective as targeting multiple pathways in a cancer cell.
Another challenge is to identify for which patients the targeted treatment will be effective. Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone.
If you find one or more implicated genes in a patient's tumor cells, how do you know if they are functional (is the encoded protein actually produced)? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?
All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene won't tell you anything about protein interactions. Are you sure that you've identified every single gene that might influence sensitivity or resistance to a certain class of drug?
Assuming you resolve all of the preceeding issues, you'll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations. And what about external facts such as drug uptake into the cell?
Gene profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, are still years away from working successfully in predicting treatment response for individual patients. Perhaps this is because they are performed on dead, preserved cells that were never actually exposed to the drugs whose activity they are trying to assess.
One of the problems with genetic tests is in evaluating the data which exists to validate the predictive accuracy of them. Generally, a large number of archival specimens are batch processed together, within a very narrow time frame, by the same research team, so all the technical variables are minimized, which makes it much easier to get good results than in a "real world" setting, where specimens are tested over a period of weeks, months, years, by different people, with different laboratory reagents, as occurs in the "real world."
Evaluating "real world" data, requires specimens that are tested as they are logged into the lab in question, in "real time." No one is publishing "real world" studies, except private laboratories performing cell-based tests, which can only do "real world" studies, because their studies require fresh, viable specimen, which must be accessioned and tested in "real time," under "real world" conditions.
#2 Aug 30, 2008
This article had nothing to do with "genetic profiles." The researchers were looking at the specific traits of tumors. The growth factor is one trait they know contributes to spread, but something they do not yet have an effective weapon for. The research discussed is a trial of a combination of drugs that might help fight that growth factor when present.
This isn't about genetic testing to see who "will get" cancer. It's about determining the best treatment for one specific subtype of breast cancer.
However, pooh-poohing genetic testing for breast cancer is ill-advised, as the people who have one of those genes have an 80% lifetime risk of developing breast cancer. One pop star's doctor has likely saved her life. She had the genetic testing because her mother had had breast cancer, and he started screening her at age 30. This probably wouldn't have been done unless she had had that genetic testing.
PERFECTION in the "real world" is not the minimum standard. It's a long-term goal. In addition, there's all kinds of "real world" data out there. My oncologist only makes treatment decisions based on approaches that have been proven to work in the real world with very specific populations.
Cell research is an important early stage of research but is not the basis for treatment decisions. And NONE Of this was about genetic testing of PEOPLE.
Since: Dec 05
#3 Aug 30, 2008
Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for individual patients.
The core of the cell is composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any of these pathways, it is important to examine the effects of drug combinations within the context of the cell. Both genomics and proeomics can identify potential therapeutic targets, but these targets require the determination of cellular endpoints.
#4 Aug 30, 2008
"Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for individual patients."
Since no one has ever claimed that,... yeah.
Yes, we know. Cancer cells are complex. Yes, if a drug could target and disrupt an important function of the cell that might be a very effective treatment.
That's what the article was about. They are researching a new way to attempt to do that with a subtype of breast cancer that is currently difficult to treat.
That's why they do pathology on the actual tumor rather than doing genetic testing to help determine treatments.
Since: Dec 05
#5 Aug 30, 2008
Sequencing the genome of cancer cells is explicitly based upon the assumption that the pathways of tumor cells can be known in sufficient detail to control cancer, an assumption that just so happens to be false. The assumption that the pathways of tumor cells can be known in a patient with metastatic cancer is logically inconsistent with the reality of tumor cell evolution. The problem is that a patient with metastatic cancer can have billions of unknown cancer cells disseminated throughout the body at unknown locations. Each cancer cell can be different. And the cancer cells that are present change and evolve with time.
The required target for the consistent and specific control of cancer is the set of all malignant cells that could evolve. Targeting a lesser set will fail. It may act to change the course, but not the flow of tumor cell evolution. It must have the ability to kill or inactivate all malignant cells in the patient (one malignant cell that excapes could multiply and cause progressive disease). It must have the ability to target cancer cells without harming normal cells or causing toxicity to the patient, and target properties of cancer that can be known, or accurately predicted.
The consistent and specific control of cancer will require a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness. A sufficient number of independent methods of cell killing must be employed so that it is too improbable for cancer cells to evolve that can escape death or inactivation. It must examine functional aspects of every cell in the body and must do so for a prolonged period of time.
Today, we have the ability to take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways, then use two, three, four or more targeted therapies, perhaps simultaneously, and be able to completely interrupt the flow of the cancer process.
#6 Aug 31, 2008
"Sequencing the genome of cancer cells is explicitly based upon the assumption that the pathways of tumor cells can be known in sufficient detail to control cancer, an assumption that just so happens to be false."
Researchers do NOT base further research on assumptions. This statement is patently false.
"ssumption that the pathways of tumor cells can be known in a patient with metastatic cancer is logically inconsistent with the reality of tumor cell evolution."
That is why this is NOT the basis for cell research in cancer. In fact the researchers are well aware that the cellular function of cencer cells change over time. This is how breast cancer cells become resistent to Tamoxifen, one very well known instance of this trait. This is why a treatment that initially seems to work stops working. And, they've known this for quite some time.
The required target for the consistent and specific control of cancer is the set of all malignant cells that could evolve. T"
That is an absurd statement, because cancer isn't one diseease. It's many different diseases with one common trait involving out-of-control growth.
"A sufficient number of independent methods of cell killing must be employed so that it is too improbable for cancer cells to evolve that can escape death or inactivation."
And this is why treatment often involves two approaches at once. This is common in chemotherapy where the patient receives two different chemo agents at the same time. The two chemotherapies will attack the cancer cell in two different ways at the same time, making it harder -- but not impossible -- for the cancer cells to survive.
"The consistent and specific control of cancer will require a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness."
Yes. That's the goal of cancer treatment: keep it from growing and keep it from spreading.
"Today, we have the ability to take a cancer specimen, analyze it, and follow those genetic changes that influence particular pathways, then use two, three, four or more targeted therapies, perhaps simultaneously, and be able to completely interrupt the flow of the cancer process."
No, we don't. This is why people are still dying of cancer.
I've received three different chemo agents, Herceptin and now an AI. My doctor HOPES that all of these treatments will guarantee that my cancer, if it had spread, could not survive all this treatment. However, it's not guaranteed. The rate of death from breast cancer has dropped, but it still happens that women who had everything I had (of course only selected patients are appropriate for either Herceptin or AI's), whose cancer was found very early, still experience a spread some years later.
There have been all sorts of recent dramatic findings. It turns out that in premenopausal women with hormone-sensitive breast cancer, combining AI with Zometa (Reclast) very significantly decreasess spread. This is a recent finding and they can only speculate why right now because they do NOT have the ability to take a cancer specimen, analyze it, and follow the genetic changes to the point that they can guarantee a positive treatment outcome.
I'm waiting with bated breath to see if this excellent outcome with Zometa carries over to post-menopausal women also. My oncologist knew this research was in the pipeline and put me on Reclast rather than an oral medication to try to prevent osteoporosis, which AI's help develop.
I urge people, when they read posts that sound quite authoritative, to print them out and take them to their oncologists, as we who have cancer need accurate information, not soap-boxing.
#7 Aug 31, 2008
Here's new research demonstrating that we don't even know everything about the functioning of breast cancer cells, much less every in and out of it as they change. We are in fact quite far from that goal.
"Estrogen Receptor-Beta Status Influences Breast Cancer Prognosis
Information from Industry
How many chances will you have to treat her metastatic breast cancer?
Learn why your first chance of response is often an important consideration.
By Will Boggs, MD
NEW YORK (Reuters Health) Aug 27 - Estrogen receptor (ER)-beta status is an important determinant of outcome in women with breast cancer treated with adjuvant tamoxifen therapy, according to a report in the August 1st Journal of Clinical Oncology.
"We believe that ER-beta examination in addition to ER-alpha/PR/HER-2 examination will further our knowledge of breast cancers and will help to optimize the treatment of the disease," Dr. Naoko Honma from Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan told Reuters Health."
See the whole article here:
Since: Dec 05
#8 Aug 31, 2008
This "assumption" is embedded in the approach described in conference presentations in the past. Sequencing the genome of cancer cells is explicitly based upon this assumption, an assumption that just so happens to be false.
Cancer is not one disease, that is why the required target for the consistent and specific control of cancer is the set of all malignant cells that could evolve.
Cancer treatment often involves many approaches at once. We have the ability to take a cancer specimen, analyze it, and follow genetic changes that influence particular pathways, then use two, three, four or more targeted therapies, perhaps simultaneously, and be able to interrupt the flow of the cancer process.
Patients are still dying of cancer because they are chasing mets with the wrong type of chemotherapeutic regimens for their type of cancer histology. Patients tumors with the same histology do not necessarily respond identically to the same agent of dose scheudle of multiple agents.
Medical oncologists select a drug and must wait to see whether it is effective on a particular patient. Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual.
And when patients develop metastatic cancer, it is often difficult to select an effective treatment because the tumor develops resistance to many drugs. For many cancers, especially after a relapse, more than one standard treatment exists.
Current testing for not only Her2/neu but also estrogen receptor is not all that accurate. Drugs can work in ways that we don't suspect. That is the purpose of functional testing (is the cell being killed, regardless of mechanism) as opposed to target testing (does the cell express a particular target that the drug is supposed to be attacking)
Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents.
It can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient.
This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free and overall survival.
#9 Aug 31, 2008
"This "assumption" is embedded in the approach described in conference presentations in the past."
"Sequencing the genome of cancer cells is explicitly based upon this assumption, an assumption that just so happens to be false."
Nope. It's a first step to do that. They have to know where the genes were if they are to perceive accurately how they change.
"Cancer is not one disease,"
Did you MISS where I said that???
"Patients are still dying of cancer because they are chasing mets with the wrong type of chemotherapeutic regimens for their type of cancer histology."
People are dying of cancer because we can't always make it go away. We do not have effective treatment for all types of cancer. We don't even know all the variants yet. See my last post showing yet another new discovery about some breast cancer cells.
"Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual."
THAT'S ALL THEY'VE GOT, and they know it won't apply to every individual, becaure there are NO treatments with 100% positive clinical results for the GREAT majority of cancers.
"Medical oncologists select a drug and must wait to see whether it is effective on a particular patient. Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual.
And when patients develop metastatic cancer, it is often difficult to select an effective treatment because the tumor develops resistance to many drugs. For many cancers, especially after a relapse, more than one standard treatment exists."
Did you MISS where I said that??? We ALL know this. Treatments don't always work.
"Current testing for not only Her2/neu but also estrogen receptor is not all that accurate. Drugs can work in ways that we don't suspect."
No kidding. You can't have it both ways, insisting that we match treatments to tumors perfectly and then admitting that we don't have enough knolwedge to do that.
Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents."
This is still in the research stage. This is NOT available and it's just wrong to keep insisting that it is.
we have NO perfect answers yet, and no laboratory tests that GUARANTEE results. HerNeu tests have been refined and they keep working on refining it more. Ditto for testing for hormone responsiveness.
Meanwhile the doctors have to work with the best information they have, imperfect though it is.
Since: Dec 05
#10 Sep 1, 2008
Have you missed what you've said? I can understand your confusion. Can you?
In life or death situations, one must make judgements based upon the preponderance of available evidence as opposed to proof beyond reasonable doubt.
It seems obvious that evidence-based medicine proponents may fail to apply this common sense standard on a consistent basis.
#11 Sep 1, 2008
"In life or death situations, one must make judgements based upon the preponderance of available evidence as opposed to proof beyond reasonable doubt."
Good. You're FINALLY reading my posts. It may "seem" to you that something is evident to you, but ... I have had a markedly different experience. My oncologist has had to make medical decisions based on the preponderance of evidence, because your arbitrary standards can't be met yet. So they go with the best information they have.
There can be serious consequences from chemotherapy, but frankly, gdp, since your wife had chemotherapy they have acquired a lot more information, new drugs, new ways to administer them, and more information about monitoring those possible side effects.
I have NO COMPLAINTS and I finished chemotherapy fairly recently. Everything they did was intended to extend my life, not shorten it. That doesn't mean nothing ever goes wrong, but in 2008, death from chemotherapy isn't NEARLY as common as death from cancer.
They do the best they can. Chemotherapy isn't perfect but they can only use the tools they have.
Of course since I had cancer I've met more people who have had it and people who had it in their personal history have come forward. NOT ONE OF THEM has your complaints about a lack of common sense. Not one of them. TO A PERSON we are all grateful for the skills of the doctors and medical staff who have saved our lives.
I am going to respond to every one of your "The sky is falling!" posts with the truth -- for me, chemo wasn't that bad and NOTHING TO FEAR. I had very few side effects and those were EASILY managed. Of course anyone would rather not have to do it, but it was just a bump in the road, and if there's anything that is certain, it is that sooner or later all of us will have some kind of serious illness. Far better to have accurate information than "chicken little" frights.
Oncologists -- AS A GROUP -- are dedicated, compassionate people. Ask questions. Ask questions of the oncology nurses who actually administer the chemo. Talk to the other people in the chemo center. Talk to your friends.
Don't let total strangers scare the bejeezus out of you. They don't know your case.
Since: Dec 05
#12 Sep 2, 2008
It is patently unfair for someone to personally attack anyone else's thoughtful opinions or information which just doesn't meet with their personal opinions. But such comes from "flat earth" ideologs.
It seems Gail that you need feed your obsession to spend all your time trashing the ideas of others. I can still read and appreciate the rational input from others, with various opinions on the issue, and ignore the space wasted trying to keep attention on yourself.
#13 Sep 2, 2008
"It is patently unfair for someone to personally attack anyone else's thoughtful opinions "
That is absurd. Your post was full of misinformation, and people dealing with breast cancer need accurate information.
I understand how to read research, and I have not seen research based on assumptions. However, I have seen you do that many times, and the one time I was able to locate one of your sources, that writer had based sweeping opinions on unproven assumptions as well.
Since: Dec 05
#14 Sep 2, 2008
Recent disclosures of fraudulent or flawed studies in professional medical journals have called into question the merits of their peer-review system. Passing peer-review is not the scientific equivalent of the Good Housekeeping seal of approval. They do not control the world's information flow, and neither do you.
Journal Editors try to be the "gatekeepers" of information (only information that they allow). If peer-review were a drug, it would never be marketed. Peer-review is nothing but a form of vetting (whether it be anger, jealousy, or whatever). Reviewers are in fact often competitors of the authors of the papers they scrutinize, raising potential conflicts of interest.
Such problems are far more embarrassing for journals because of their claims for the superiority of their system of editing. Journal Editors do not routinely examine authors' scientific notebooks, they rely on peer reviewers' criticisms.
Then there is the problem with respected cancer journals publishing articles that identify safer and more effective treatment regimens, yet few oncologists are incorporating these synergistic methods into their clinical practice. Because of this, cancer patients often suffer through chemotherapy sessions that do not integrate all possibilities.
Sorry Gail, progressive patients do not want to play in your sandbox.
#15 Sep 2, 2008
"Peer-review is nothing but a form of vetting (whether it be anger, jealousy, or whatever)."
"Vetting" and "venting" aren't the same thing. Peer review is a start but not the be-all and end-all of quality. For instance, you might write a peer-reviewed article -- for the Flat Earth Society. In that case, the peers reviewing that article would be people who believe the Earth is flat.
"Then there is the problem with respected cancer journals publishing articles that identify safer and more effective treatment regimens, yet few oncologists are incorporating these synergistic methods into their clinical practice."
Just because one study showing something has been produced does NOT mean MD's should act on that one study. People's lives are at risk. A first-class example of this is Herceptin. There is ONE study showing that nine weeks of Herceptin is as effective as a year of it. I of course was interested in this, as Herceptin is extremely expensive and I have no health insurance.
My oncologist has worked hard with me to keep costs down, but strongly advised against this approach (he has no financial interest in how much Herceptin I got, by the way) because there was only the one study, it was relatively small, and the great majority of research showing effectiveness was based on a year's treatment.
Frankly you sound paranoid about research. I would like to meet the oncologist who does not know how to read research, and I think the notion that one researcher would tear down another researcher's research out of jealousy is absurd.
Sorry, Greg, but I'm a progressive patient and I like my sandbox very much. I stay up-to-date with the research, and so does my oncologist. I think you throw sand when people disagree with you, since you have repeatedly gotten into attack mode.
In fact my oncologist has acted on new research before it was published. This is why I get Reclast instead of a pill form to prevent osteoporosis. He knew what was in the pipeline before it was published.
However, he does this with great judgment. I am so grateful to him. By the way, that's only one of several ways my treatment was modified during the course of it, based on new research.
Since: Dec 05
#16 Sep 3, 2008
Your own comments always bite of conspiracy theories, a diversion to counter ideas other than yours. I suppose anyone who dared question and expose Vioxx, Ketek, Zyprexa and the endless list of harmful and/or deadly drugs would have also been on your target list as a paranoid ignoramus. After all, the drug companies and their 'factual' trials 'proved' that these blockbuster drugs were safe; the FDA studied the 'facts' and said they were safe and effective.
The format of point by point rebuttal of every single sentence, line by line is rather boorish. I would rather converse. I do read posts when they are written as thoughtful essays. Some maybe long, but very readable. Trying to read someone slicing and dicing and dissecting every sentence I write is boorish. The point by point, line by line, tit for tat rebuttal style is indeed fundamentalism.
Using selective quotation to make someone appear to hold positions which they do not hold seems to be a favorite pastime for Gail. I would suggest those who may be alarmed by these kinds of quotations to read the information in its entirety. A scientific communication should be judged on the quality of its content, not by alarmist quackwatch attitudes.
#17 Sep 3, 2008
The tests do NOT YET EXIST to to tissue-typing and determine the optimal treatment for breast cancer patients yet. This quote demonstrates how incomplete the information is even regarding well-known subtypes of cancer,and yet treatment results vary.
"Luminal tumors are characterized by expression of the estrogen receptor, which is usually accompanied by expression of the progesterone receptor. The protein kinase HER-2/neu is upregulated in HER 2 overexpressing tumors. Basal-like and unclassified tumors constitute the triple-negative phenotype.
"Compared with luminal tumors, both HER 2-overexpressing and triple-negative tumors have a poorer prognosis," the authors said. "However, to our knowledge, differences in the epidemiology of these subtypes are not well defined."
#18 Sep 3, 2008
"Your own comments always bite of conspiracy theories"
Not in the slightest. I hold NO concpiracy theories, either about medical issues or any other issues on this planet.
And, I don't disagree with everyone. I agree with the great number of oncologists. I do, however, disagree with you frequently. i think you make a lot of unsubstantiated statements, and I don't think you understand research nearly as well as you think you do.
I have never quoted you just to distort your viewpoints. You, however, have done that to me several times.
Don't attack the poster. Challenge the contents. The only reason I can see for you to attack me personally (and you do it in every discussion we are both in) is because you can't defend your own thoughts.
You might rather "converse," but since your posts often contain wide-ranging conclusions based on invalid assumptions I will not be doing that. I will continue to refute inaccurate information. It doesn't matter to me who posts inaccurate information.
Since: Dec 05
#19 Sep 10, 2008
I don't know where Gail is coming from making totally uniformed statements about me. One must be objective and decide at what point the benefits of drugs truly outweigh the risks they present. Some of the risks are minor and others are tolerable in that they are reversible, short-term or non-life threatening. Many of the risks are extremely serious and are difficult to balance against relief from anything but the most severe symptoms. For some people the risks may be acceptable, for others, not.
Chemotherapy is supposed to prevent the metastasis of a cancer. Are we crediting chemotherapy with too much false hope for preventing tumor spread? I don't think cancer researchers have substantiated the case for chemotherapy.
Despite the media hype about the breakthroughs, clinical trials of cancer drugs are failing with painfully predictable regularity. "Chronic control" has replaced "cure" as the goal of many in the research community. Some researchers say insufficient consideration has been given to the requirements for the "cure" of cancer without significant toxicity to the patient and without severe side effects.
Most cancer research has focused on discovery of the differences between cancer cells and normal cells. The hope has been that these differences can provide a basis for understanding and targeting cancer cells. Drugs have been made to target and kill cancer cells. But the truth is that despite these drugs, patients continue to suffer and die of cancer at virtually the same rate. The conventional approach is not working, we can do better.
#20 Sep 10, 2008
The only thing I know about any poster here is the content of his or her posts. Cancer researchers HAVE substantianted the case for chemotherapy: IT SAVES AND EXTENDS LIVES.
Yes, we all know that not all cancer drugs do well in trials, and certainly there is no "magic bullet." "Chronic control" is the goal when cancer has spread because the alternative is to let the person die a rapid and difficult death. Some CRITICS may say "insufficient consideration has been given to either looking for the "cure" of cancer, but those people are ill-informed, as cancer is many different diseases with many different treatment and many different ways to fight it.
Actually, most cancer research has NOT focused on discovering the difference between "cancer cells and normal cells." The research has been much more tightly focused than that BECAUSE cancer isn't one disease but many diseases with one common trait. Unfortunately that common trait does not provide a path for a common cure.
Yes, gdp. We know people still die of cancer, and EVERYONE knows we don't have all the answers yet, and no one wants treatments to have severe side effects.
But in fact people do NOT continue to suffer at the same rate and die at the same rate they did even 20 years ago. Survival rates for most of the various types of breast cancer have risen because of all the treatments you are trying to downplay.
We would ALL like to see it better, but no people more than those who have had breast cancer and realize that it can come back at any time and almost anywhere. You don't have to distort the facts to make the OBVIOUS point that there's more work yet to be done.
Both Herceptin and the development of AI's are saving lives. They both fall OUTSIDE the umbrella of chemotherapy. They ARE "targeted therapy." Often targeted therapy is not chemotherapy, and yet although you described the concept, you never mentioned it.
If I live, cancer free, for another 15 year, there will still be that chance that all that was achieved for me was "chronic control." If "chronic control" means 15 cancer-free years I will be overjoyed with "chronic control." That's what I'm hoping for, whatever it's called, to live to see grandchildren, more times with my friends, more time singing, sailing and making pots. If that's chronic control -- BRING IT ON.
You are still trying to put down oncologists, who in my experience (three different ones) work very hard to stay up-to-date and pick treatments for their patients with careful thought and preparation. In my world they're heroes.
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