Why, oh why, did I look at GreenMedInfo again?
You remember GreenMedInfo? It's yet another wretched hive of scum and quackery, but with a twist. Its proprietor, Sayer Ji, thinks he's an expert at interpreting the biomedical literature. Unfortunately, as he demonstrates time and time again with depressing regularity, he is nothing of the sort. In reality, what Ji is an expert at is cherry picking medical studies and torturing them until they confess agreement with whatever quack idea he's currently espousing. In the wake of the news coverage of Angelina Jolie's decision to have her ovaries removed because she had a dangerous mutation in the gene for BRCA1, a mutation that gave her a very high risk of breast and ovarian cancers, he demonstrated that rather well. Indeed, last week, I deconstructed his criticism of Jolie's decision and the incredibly faulty scientific and logical reasoning behind it. Other than a minor Twitter confrontation with Ji the day after I posted, I moved on after having refuted his nonsensical and scientifically ignorant arguments because, well, you have to move on in blogging.
Unfortunately, Ji revisited the topic of BRCA1 mutations just yesterday with an equally fallacious article about BRCA1 mutations entitled Is BRCA ("Breast Cancer Gene") A Death Sentence? I could have told Ji the answer if he had asked me and saved him a lot of trouble. The answer is no. BRCA1 mutations predisposing to breast and ovarian cancer are bad, but they are hardly a "death sentence." Of course, Ji, demonstrating that the intended correct answer to any question used as the title of an article is no, goes beyond that basic answer to try to argue again that BRCA1 mutations don't matter and that "genes are not destiny," basing his claims on a recent systematic review and meta-analysis by van den Broek et al entitled Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis. It is exactly what its title says, a meta-analysis of studies examining the effect of BRCA1 mutations on breast cancer survival. As is his wont, Ji begins the article very confidently, amazingly overconfidently, actually:
What we think we know about the BRCA (Breast Cancer Susceptibility Associated) genes causing cancer is patently false, according to a new meta-analysis on the extant literature on the subject of these gene variations on breast cancer survival prognosis.
No. Not exactly. Let's just say that this meta-analysis doesn't say what Ji thinks it does, at least nowhere near to the level the he does. Ji read this meta-analysis and concluded that it tells us that "what we think we know about BRCA1 is false." It's not, except in Ji's mind. First off, this meta-analysis says nothing about BRCA1 mutations causing cancer. That's just the underlying assumption of the review, because it's so well-established that certain BRCA1 mutations confer a vastly elevated risk of breast and ovarian cancer that no cancer doc seriously argues against that contention any more. What this meta-analysis looks at is one question: Whether breast cancers associated with BRCA1 are deadlier than basic run-of-the-mill breast cancers, which is a common belief among physicians, one not without evidence to support it. Not surprisingly, Ji's interpretation of the study at one point is so spectacularly wrong that it's downright hilarious:
A groundbreaking new meta-analysis published in PLoS titled,"Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis", calls into question the value of using BRCA1/2 gene status to determine breast cancer survival prognosis, as is common practice today. This implications of this research may have wide-ranging effects as the present climate, following Angelina Jolie's high profile decision to have prophylactic breast, ovary and fallopian tube removed due to her perceived "genetic inheritance," is to equate BRCA status with bona fide and mathematically calculable disease risk certainty.
Jolie's decision to subject herself to multiple prophylactic organ removal was based on the premise that her BRCA mutations would result in an 87 percent lifetime risk of developing breast cancer and up to 54 percent chance of ovarian cancer, as prognosticated by her doctors. The notion that BRCA genes have full or near full penetrance (the ability of a mutation to cause clinically identifiable disease) has profound implications for the health of millions of women who rely on these predictions to make life and death medical decisions.
I've dealt with this nonsense before, of course, but this is the same nonsense with a different spin. So I consider it useful to deconstruct that different spin. First off, this meta-analysis does not in the least bit call into question the finding that certain BRCA1 mutations can confer an 87% lifetime risk of breast cancer and a 50% lifetime risk of ovarian cancer. What it calls into question is whether the breast cancers caused by BRCA1 are actually deadlier than cancers not associated with such mutations. It's been commonly thought that they are, and, in fact, there's a fair amount of evidence that they are. The conclusion of this meta-analysis is also not a new finding. For example, a year and a half ago, Huzarski et al published a study examining ten year survival in cancers with BRCA1-positive breast cancer. Basically, 3,345 women with stage I to III breast cancer under the age of 50 were tested for three founder mutations in BRCA1. It was found that 7% carried a BRCA1 mutation and that the ten year survival rate in BRCA1 carriers and non-carriers was very similar, 80.9% and 82.2%, respectively, with no statistically significant difference between the two. Basically, what the meta-analysis shows is that the evidence is inconclusive as to whether BRCA1-associated breast cancers result in worse survival.
So why is Ji harping on this?
Basically, it's the same nonsense that I discussed last time and expanded upon elsewhere. Ji is heavily invested in "proving" that cancer is not a genetic disease and that whatever woo du jour he favors, be it diet, lifestyle, supplements, or whatever, can prevent or reverse virtually any cancer. Cancers due to a genetic predisposition, such as BRCA1-induced breast and ovarian cancers are a direct challenge to that concept, and Ji cannot allow his readers to accept the scientific consensus with respect to them because then they might start doubting that what he's selling will do them any good. So, like last time, he goes on the attack, ignoring the fact that the very meta-analysis that he uses as his jumping off point didn't even conclude that BRCA1-associated breast cancers are deadlier, only that the evidence that they are is inconclusive.
Last time around, Ji conflated absolute risk of cancer with relative risk in BRCA1 mutation carriers, shamelessly quoting studies of sporadic breast and ovarian cancer as though they had any more than minimal relevance to cases of BRCA1-induced cancers. He's even more shameless in spinning the question of overdiagnosis and overtreatment. For instance, he states that, according to a New England Journal of Medicine study, 1.3 million US women were "wrongly diagnosed and treated in the past 30 years." Uh, no. Not exactly. The study to which Ji refers is, of course, Archie Bleyer and H. Gilbert Welch's 2012 study that found that approximately 30% of mammographically detected breast cancers were overdiagnosed. I've discussed Ji's characterization of this particular study before. "Overtreatment" doesn't necessarily mean "wrongly treated." In fact, arguably it does not. As we like to say in medicine, the retrospectoscope is 100% accurate. The problem was (and is) that as yet we do not and cannot know for mammographically-detected breast cancers which lesions will progress to threaten the life of the woman and which will not. Knowing what we know, we therefore are obligated to treat all screen-detected cancers as though they are potentially deadly. Until we have the tools to do that, we either have to treat them this way, or stop or decrease screening.
Ji continues to use loaded language here:
And so, previous studies on BRCA1/2 gene variations and the incidence of breast cancer have not taken this massive statistical inflation of non-cancerous "breast cancer diagnoses" into account, further feeding the illusion that having an identified BRCA mutation equates to having a inexorably higher risk of a deadly cancer, when in fact, in cases where BRCA was linked to so-called early stage or 'stage zero' lesions such as Ductal Carcinoma In Situ (DCIS), this condition was recently determined to be intrinsically benign by a NCI-commissioned expert panel and therefore should not be lumped together with other truly deadly forms of breast cancer, as is still common practice today despite the growing body of evidence against it.
DCIS "intrinsically benign"? That's a rather obvious misrepresentation of what the NCI panel actually concluded. This is the paper to which Ji refers. It's by Laura Esserman, Ian Thompson, and Brian Reid. Yes, Esserman et al, summarizing the NCI panel's findings, argue that DCIS and precancerous prostate lesions should not be called cancer, but they hardly argue that they are "intrinsically benign." In fact, they write:
Change cancer terminology based on companion diagnostics. Use of the term “cancer” should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. There are 2 opportunities for change. First, premalignant conditions (eg, ductal carcinoma in situ or high-grade prostatic intraepithelial neoplasia) should not be labeled as cancers or neoplasia, nor should the word “cancer” be in the name. Second, molecular diagnostic tools that identify indolent or low-risk lesions need to be adopted and validated. Another step is to reclassify such cancers as IDLE (indolent lesions of epithelial origin) conditions. An example is the reclassification of grade 1 papilloma to urothelial neoplasia of low malignant potential. Presciently, the rationale for reclassifying papilloma and grade 1 carcinoma as “papillary urothelial neoplasia oflow malignant potential” was “to take the lowest grades of tumor, the most benign-appearing lesions, and remove the word carcinoma.” A multidisciplinary effort across the pathology, imaging, surgical, advocate, and medical communities could be convened by an independent group (eg, the Institute of Medicine) to revise the taxonomy of lesions now called cancer and to create reclassification criteria for IDLE conditions.
In other words, lesions with a relatively low chance of progressing to cancer should be reclassified. This is a completely reasonable suggestion. However, Esserman et al make it clear that, while these lesions should probably not be called "cancer," they are by no means "intrinsically benign," as Ji falsely characterizes them. In any case, Ji claims that the existence of overdiagnosis somehow calls into doubt the high lifetime risk of breast cancer conferred by high risk BRCA1 mutations. It's a profoundly stupid argument, and I'll show you why. Let's, for instance, assume an 87% lifetime risk of breast cancer from Angelina Jolie's BRCA1 mutation, as her doctors told her she had. Now, let's do something as simplistic as Ji's reasoning but, in the context of his argument that overdiagnosis "inflates" the risk of breast cancer due to BRCA1 mutations. Let's take a rate of overdiagnosis of 30%, meaning that any cancers detected in our hypothetical situation examining BRCA1 carriers are 70% likely to be "real." Now, 0.70 x 0.87 = 0.61, or a 61% lifetime risk of developing a life-threatening breast cancer. Even using Ji's simplistic model, that's still pretty damned high. In brief, Ji's handwaving and invoking of overdiagnosis are nothing more than an obvious smokescreen. Overdiagnosis does not even come close to explaining the high risk of breast cancer in BRCA1 carriers, and I'm not even taking into account how overdiagnosis declines as disease prevalence goes up. It is, however, known that DCIS is roughly as prevalent in BRCA1 mutation carriers as in non-carriers, but occurs at an early age, evidence in favor of the premalignant character of a lot of DCIS.
Ji also resurrects his claim that the existence of Borderline Ovarian Tumors (BOTs), which can also be overdiagnosed and overtreated, somehow inflate the number of cancers attributed to BRCA1. He cites a JAMA study he cited last time that "found that 5 times more women are diagnosed and treated with ovarian cancer than actually have it -- indicating a massive problem that is not being taken into account by most literature on the role of BRCA mutations in cancer risk because these studies accept diagnosed cancer uncritically as actual cancer which is simply not the case due to the still largely unaccounted for issue of overdiagnosis." This study, of course, is one big reason why we don't screen the general population for ovarian cancer using transvaginal ultrasound and CA-125 blood tests. The study found that for ovarian cancer screening using these tests doesn't work; it doesn't decrease mortality from ovarian cancer and results in a lot of overdiagnosis.
Again, however, screening the general population is a very different case than observing women with high risk BRCA1 mutations for the development of ovarian cancer. Let's just put it this way, even if, in general, overdiagnosis due to screening didn't decline precipitously with increasing prevalence of a disease, we have plenty of evidence that prophylactic surgery is effective, that intervening, as was done with Angelina Jolie, to prophylactically remove the tissue at high risk for cancer dramatically improves overall survival of these women. Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with high risk BRCA1 mutations by at least 90%. (See, for example, Hartman et al, 1999; Domchek et al, 2010; Rebbeck et al, 2004; Meijers-Heijboer et al 2001.) Removal of the ovaries is also highly effective in reducing mortality from ovarian cancer in such patients, lowering the risk by 70-90%. (See, for example, Kauff et al, 2002; Kauff et al, 2008; Finch et al 2014.) That prophylactic oophorectomy to prevent ovarian cancer and prophylactic bilateral mastectomy to prevent breast cancer in carriers of high-risk BRCA1 mutations are highly effective is not even controversial. Such recommendations are "baked" into major evidence-based guidelines, like those of the NCCN, as a significant option for women found to have such mutations to consider. Other options exist, such as enhanced screening (which has not been shown to be effective in ovarian cancer) or chemoprevention.
If you want to get an idea how mendacious Ji is, look no further than this passage:
Furthermore, prophylactic removal of the ovaries before age 45 (Jolie is 39) has been linked to 67% increased mortality risk, according to a 2006 study published in Lancet Oncology, indicating that organ removal as a generic form of "cancer prevention" may be doing the opposite of 'saving lives' as widely claimed.
That 2006 study? Take a look at just the abstract, and you'll see why Ji is full of it. Specifically, the Method part:
From an existing cohort of all women who underwent unilateral or bilateral oophorectomy while residing in Olmsted County, MN, USA, in 1950-87, we analysed those who had received an oophorectomy for a non-cancer indication before the onset of menopause. Every member of the cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy.
Yes, these were women who had their ovaries removed for non-cancer indications before 1987. I note that BRCA1 was not identified as a gene until 1990 and was not cloned until 1994. I also note that this study examined women who had their ovaries removed for non-cancerous reasons. Finally, Ji left a big finding of this study out:
However, mortality was significantly higher in women who had received prophylactic bilateral oophorectomy before the age of 45 years than in referent women (hazard ratio 1.67 [95% CI 1.16-2.40], p=0.006). This increased mortality was seen mainly in women who had not received oestrogen up to the age of 45 years. No increased mortality was recorded in women who underwent unilateral oophorectomy in either overall or stratified analyses.
In other words, the increased mortality of women who had their ovaries removed before age 45 was mainly seen in women who didn't undergo estrogen replacement therapy until age 45 after their surgery. The authors also noted:
Although prophylactic bilateral oophorectomy undertaken before age 45 years is associated with increased mortality, whether it is causal or merely a marker of underlying risk is uncertain.
So, yes, Ji misrepresented another study. Quelle surprise. He also resurrects his observation that BRCA1-associated ovarian cancers might be somewhat less aggressive and more sensitive to chemotherapy than sporadic cancers, to which I again say: So what? It's still a plenty deadly cancer, and certainly no advantage is seen in BRCA1-associated breast cancers. In fact, another 2015 meta-analysis published in a better journal and more comprehensively looking at both breast and ovarian cancer found that BRCA1-associated ovarian cancer does have a better prognosis but that BRCA1-associated breast cancer portended a significantly worse overall survival, in disagreement with the meta-analysis Ji cited.
Ji finishes with his real message:
And therefore, what do we really understand about BRCA gene 'mutations' when there are over 500 that have been identified, and whose complexity and role in health and disease are still not yet understood? The truth is that the linear and deterministic gene > trait > disease risk/prognosis way of thinking is archaic, and reflects the type of hubris that should have been sloughed off after the first draft of the human genome project in 2005 found that the 'holy grail' of molecular biology was not to be found in the genome, but in the interstitial space of its interactions with the myriad factors 'beyond the control of the gene,' the realm of epigenetics, which involves everything from the food your mother ate, your in utero exposures, to your breast feeding duration, the toxins and toxicants you were and are exposed to, your way of thinking, attitudes and beliefs and the downstream physiological effects they have, ad infinitum.
Ironically, the notion that genes determine destiny is more than just an idea but a reality for those who believe it and act on the meme, putting ideology into practice in their biology and medical decisions. This is why acknowledging the research that calls into question biological determinism and medical fatalism is so powerful and why we hope our readers continue to explore the primary literature itself as it expands and transforms the often out-dated knowledge base that conventional practice is still under the illusion is reflective of the truth.
Ji sounds rather like a creationist, doesn't he, harping on the "interstitial space" of the interactions of the genome with various other factors? Oh, and the attacks on genetic "determinism," too. He also makes a bald-faced appeal to ignorance. Yes, there are hundreds of BRCA1 mutations. Yes, we don't know the significance of a lot of them. Those two observations, however, completely ignore the fact that we do know a lot about the significance and cancer risk associated with quite a few of those hundreds of BRCA1 mutations. Just because we don't know the significance of a lot of them doesn't mean we don't know the significance of any of them. We do. Then Ji just repeats the same quack view of epigenetics, which is represented as a magic process by which humans can completely control their health and biologic destiny, genes be damned. It's a dangerous delusion.
There's a reason why Sayer Ji is dangerous. In my opinion, he advocates quackery, but he tries very hard to put a sheen of science on it. Because he is skilled at cherry picking the literature and seemingly "talking the talk" of biomedical research, he can sound quite convincing to lay people, even as real scientists who actually know something about the topics he's writing about cringe as they read his simplistic and misleading misrepresentations. Actually, we either cringe or we laugh (or both), but it's hard to laugh for too long at Ji's ignorance. The reason is that, as ridiculous as I find Sayer Ji, I know that that his advice, if followed, will lead to the preventable deaths of women with BRCA1 mutations.
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So to sum up, if you are diagnosed with breast cancer, it is not crucially important whether it resulted from BRCA1. But if you have BRCA1, you are at heightened risk of breast cancer. Meanwhile Sayer Ji lies a lot and would like to sell people his anti-cancer rock.
Yep.
@HDB
Sheesh! Think you could've used a few more words? Why can't you embrace brevity like Orac does?
Ah, Sayer Ji. The man who advised diabetic people to stop taking insulin, because it is nowadays made in yeast or bacteria.
@ hdb
I believe you got the gist of it. Well, the last one was already common knowledge :-)
"So to sum up, if you are diagnosed with breast cancer, it is not crucially important whether it resulted from BRCA1."
Well, it appears it's not crucially important to your breast cancer prognosis, but obviously important relative to your risk of getting contralateral breast cancer or ovarian cancer, as well as important to relatives who may not know they are gene carriers.
Yes. BRCA1 mutation status influences decisions with respect to bilateral mastectomy and eventually oophorectomy, genetic counseling and testing of offspring, etc.
This requires the underscores from the original in order to be fully appreciated.
Then again, after about three paragraphs of the original I was starting to question my assumption that Ji is a native English speaker.
Sajer Ji is an expert at manipulating science to fit his conclusions. It is a fascinating example of motivated reasoning. He is not as obviously unhinged as Mike Adams and has attracted several cranks with credentials (like Dr. Kelly Brogan) to his cause. This makes him much more dangerous, than Mike Adams, as I believe most people can see that Adams is a crank. But Sayer blinds them with fancy science and threatens to sue his critics into silence. I am surprised this has not happened to you, Orac, and I hope it does not.
This is incredibly scary. I had to read up on this guy and his diabetes claims. It would lead into the same thing we see with chemotherapy; diabetics who failed to control using diet would be blamed for "not doing it right" with their diets when in fact diabetics who do everything "right" sometimes need to go on medication at some point in time.
I couldn't help but notice his claims include the "GMO" tropes as well. Seems there isn't a conspiracy this guy doesn't like.
And I really have to wonder: is this guy just reading the abstracts?
Then again, after about three paragraphs of the original I was starting to question my assumption that Ji is a native English speaker.
I've always assumed he is an immigrant. His surname sounds Chinese to me (there is a scientist in my field with the same surname, and the latter is definitely Chinese). Depending on what transliteration system you use, his given name might be Chinese, too. Sayer Ji doesn't have a Wikipedia page (yet), so I don't know where he was born, but he is now in the US (specifically Naples, FL). The first page of Google results for him includes, along with his LinkedIn and Facebook pages, an Orac post about him.
@ Eric Lund:
He has a bit of a bio ( on his bit of an education) @ Sayer Ji.com. At first I though that 'Ji' was a title of respect used by those with an Indian religious background but it appears that he is indeed 'D. Sayer Ji' as written on on his 'thesis' ( for a BA yet) from Rutgers U in.... wait for it, Philosophy. **
He studied at a Zen monastery in NY and has a list of other supposed qualifications but surprisingly, no woo-bent or mail away PhD.
Ji has recently joined in with Louise Habakus, Brogan and Lawrence Pavlevsky at Fearless Parent.com ( since MacNeil dropped out) and its eponymous PRN radio show. They will be keynote woo spewers at Autism One.
Also Naples Florida is haunted by Gary Null who has a 30 acre estate there - which is -btw- for sale, reduced price, for a year or two.
** although smart people often have that type of degree, I doubt he's one.
Oh, and he enjoys being in a drum circle.
A little more digging...
it appears that the Fearless Ones are no longer on PRN ( it only has old shows) . Instead listeners are asked to use the new stylie phone radio rather than internet radio.
Ah, Florida.
Charles Pierce, hands-down the funniest writer covering American politics, discussed "Florida Man" in another context and came up with this gem:
Actually, it says "Douglas S. E. Ji" (PDF).
Just to underscore what Orac said: The study on ovarian cancer reported in the JAMA article was a very large study designed to test the use of regular ultrasounds and CA-125 monitoring to detect ovarian cancer. The hope was that monitoring would catch ovarian cancer in its early stages, when it's curable. It didn't work, The strategy produced far too many false positives and resulted in far too many unnecessary surgeries. And the women diagnosed with ovarian cancer during the study were still diagnosed with late-stage cancer. The article does not represent standard practice.
Anyone reading the JAMA article can see that it's a report on an experiment, not a critique on standard practice. Ji's comments on it are ridiculous.
Ji's comments on borderline ovarian tumors (BOTS) are a joke. The genetic mutations that give rise to BOTS are very different from the mutations that result in high-grade ovarian cancer. The genetic distinctions have been known for years and the histological distinctions have been known for decades. Borderline tumors were over-treated 50 years ago. They are not over-treated today, nor are they counted as a BRCA-related condition. In fact, most statistics on ovarian cancer specifically omit borderline tumors -- the SEER database, for instance. Clinical trials for ovarian cancer exclude patients with borderline tumors. BOT diagnoses do not cause any skewing of ovarian cancer statistics.
@ Narad:
The paper ( Independent Study) to which he links @ Sayer Ji.com./ Education Experience says "D. Sayer Ji" which in turn links to Green Med Crapo.
Here's a thought: Isn't removing the tissues that are most likely to be affected by BRCA1 just about the biggest epigenetic change possible? For some definition of epigenetic at least?
@Denice
The Florida property records confirm the Douglas.
Here’s a thought: Isn’t removing the tissues that are most likely to be affected by BRCA1 just about the biggest epigenetic change possible? For some definition of epigenetic at least?
"We checked the biohazard bin, and the DNA in your ovaries definitely seems to be substantially demethylated. Also, they are beginning to smell."
@ Narad:
Heh. He probably thought it didn't sound hip enough.
Whereas David, Daniel, Denis, Devon, Dylan, Desmond or Damon would be.
Denice, I'd argue that having a last name as a first name lends a certain faux gravitas, which is what he was looking for. Which sounds better on a byline, Doug or Sayer?
@ shay:
Sure. But he also wanted to link to his thesis.
So, "D" it was.
I was briefly hoping that it would prove to be something hopelessly fake such as "Dharma."
My thought EXACTLY.
Or else 'Dhani' or suchlike.
Sayer might not be perfect, but I find most of his information accurate. Whether or not genes have much to do with cancer is a side issue to what decisions he wants people to make. Sayer wants people to stop eating carcinogens for the most part and eat cancer fighting foods. He does much more good than harm. If someone were convinced that genetics have nothing to do with cancer risk, so what? I'm sure their decisions would be unaffected.
Oh, Ji's information is usually accurate. It's how he cherry picks and misinterprets that information that's wildly deceptive and fallacious.
I deeply respect your work ORAC, but this meta-analysis does cast doubt upon popular notions of the penetrance of BRCA genes. I'm a skeptic, as you are, but in the sense that I rely on evidence not quack hypotheses. In this instance, Ji does reference compelling evidence.
No, it doesn't do anything of the sort. It doesn't even look at the penetrance of BRCA1 genes. What it does is to look at studies comparing outcomes between patients with breast cancer who do carry a deleterious BRCA1 mutation and patients with breast cancer who do not. It says nothing about the likelihood of BRCA1 mutations causing cancer.
Do you even know what "penetrance" means? I don't think you do.
Hello everyone. Here's an MD you may know, Christine Northrup harping on some of the same concerns. Can anyone here deconstruct her minimization of the BRCA genes' role in breast cancer? http://www.drnorthrup.com/the-other-side-of-angelina-jolies-double-mast…
Other than the bit about vitamin D and emotional issues, it's pretty much the same nonsense as Ji's claims. As for the rest of it, it's cherry picking and misrepresentation. Basically, I dealt with most of what she claims between this post an my previous post:
http://scienceblogs.com/insolence/2015/03/26/the-quack-view-of-preventi…
Sorry, meant to post the study itself: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120189
The conclusion is rather unequivocal: "Conclusions
In contrast to currently held beliefs of some oncologists, current evidence does not support worse breast cancer survival of BRCA1/2 mutation carriers in the adjuvant setting; differences if any are likely to be small. More well-designed studies are awaited." Am hoping someone, if not ORAC himself, can elaborate further on how this meta-analysis doesn't cast doubt on BRCA's cancer-causing role.
Thank you
James. You sound like a quack. Didn't you read ORAC's article?
James should note the term "in the adjuvant setting." That means with adjuvant therapy. Also, as I pointed out, this isn't the only meta-analysis; a better one published in January 2015 that looked at BRCA1 in breast and ovarian cancer disagrees. I even cited that meta-analysis. Silly James.
Really? Seems the climate here is to attack those who question the party line by pointing towards the evidence itself. Hate to say it, but that kinda makes me feel sympathetic for Ji, since he is at least focusing on research that challenges the status quo. Why can't we focus on the research itself and discuss its weaknesses instead of attacking those who are actually skeptics.
Your comments thus far in this thread do not give me the impression that you are a skeptic.
Thanks ORAC. That helps. I didn't get the point about adjuvant. Silly? Hmmm
Here's a study I have been meaning to ask you about ORAC (take note Surgeon in Arms): http://www.ncbi.nlm.nih.gov/pubmed/21996169
"Because the cumulative incidence among controls did not reach that of the screened group, we believe that many invasive breast cancers detected by repeated mammography screening do not persist to be detected by screening at the end of 6 years, suggesting that the natural course of many of the screen-detected invasive breast cancers is to spontaneously regress."
Seems like if this is possible, the entire viewpoint of BRCA and gene-determined disease should be reconsidered, no?
Holy hell you're obtuse. In the course of two posts, the first post from a week ago and this one, I explained exactly why studies showing a higher than desirable rate of mammographic overdiagnosis do not call into question the "entire viewpoint of BRCA1 and gene-determined disease." I explained it in a slightly different way in each post for two explanations.
You do understand, don't you, that there's a huge difference between screening the general population for breast cancer (which is what that study you cited is about) and surveilling women with BRCA1 mutations that put them at a high risk of breast cancer? And that there's a big difference between using prophylactic surgery to prevent disease in patients at very high risk of that disease compared to screening a general population at a much lower risk for that disease?
He seems to have fairly recently* "opted out" from having his Lee County mug shot and arrest date listed on openpasts.
This could be fun.
* The March 16 G—le cache still has a thumbnail entry, which is now gone.
Yup, verified quack. Who cares what you have to say when you defend idiots.
James: Breast cancer is not epigenetic. You can't blame environmental exposures on SNPs - it's impossible. Also, this study about spontaneous tumor regression is bull. Not sure where you dug that crap up.
Ding!
Seriously Surgeon? So Lancet Oncology is a low impact journal not worth recognizing?
James, what is your point? Are you saying the immune system can just destroy cancer at will? That's insane and dangerous. Don't you read ORAC's blog regularly? Ridiculous.
All I am asking is that you tell me an alternative explanation for this Lancet study finding. Here is the whole thing:
Lancet Oncol. 2011 Nov;12(12):1118-24. doi: 10.1016/S1470-2045(11)70250-9. Epub 2011 Oct 11.
Natural history of breast cancers detected in the Swedish mammography screening programme: a cohort study.
Zahl PH1, Gøtzsche PC, Mæhlen J.
Author information
Abstract
BACKGROUND:
The natural history of screen-detected breast cancers is not well understood. A previous analysis of the incidence change during the introduction of the Norwegian screening programme in the late 1990s suggested that the natural history of many screen-detected invasive breast cancers is to regress spontaneously but the study was possibly confounded by use of hormone replacement therapy in the population. We did a similar analysis of data collected during an earlier period when few women were exposed to hormone replacement therapy.
METHODS:
We compared cumulative breast cancer incidence in age-matched cohorts of women living in seven Swedish counties before and after the initiation of public mammography screening between 1986 and 1990. Women aged 40-49 years were invited to screening every year and women aged 50-74 years were invited every 2 years. A screened group including all women aged 40-69 years (n=328,927) was followed-up for 6 years after the first invitation to the programme. A control group including all women in the same age range (n=317,404) was also followed-up for 6 years--4 years without screening and 2 years when they entered the screening programme. Screening attendance was much the same in both groups (close to 80%). Counts of incident invasive breast cancers were obtained from the Swedish Cancer Registry (in-situ cancers were excluded).
FINDINGS:
Before the age-matched controls were invited to be screened at the end of their follow-up period, the 4-year cumulative incidence of invasive breast cancer was significantly higher in the screened group (982 per 100,000) than it was in the control group (658 per 100,000) (relative risk [RR] 1·49, 95% CI 1·41-1·58). Even after prevalence screening in the control group, the screened group had higher 6-year cumulative incidence of invasive breast cancer (1443 per 100,000 vs 1269 per 100,000; RR 1·14, 1·10-1·18).
INTERPRETATION:
Because the cumulative incidence among controls did not reach that of the screened group, we believe that many invasive breast cancers detected by repeated mammography screening do not persist to be detected by screening at the end of 6 years, suggesting that the natural course of many of the screen-detected invasive breast cancers is to spontaneously regress.
FUNDING:
ORAC? Can you help me with this ridiculous study please. James is probably putting tin foil on his head as we speak.
I am not saying that the immune system killed the cancer Surgeon. I'm just pointing out that the Lancet article states regression of tumors spontaneously is possible.
When we start asking questions like this it just distracts from the women who need help now: screening, gene testing, and good surgical and drug treatment are the only proven ways to help them. You suggesting they vitamin C?
I wonder how the court date went.
Here's another one touting Natural Cures for BRCA ORAC: Dr. Dach who claims selenite normalizes BRCA mutations: "Angelina Jolie, surgical strategies for cancer prevention, and genetics denialism (revisited)" http://jeffreydachmd.com/2015/03/angelina-jolie-brca-gene/
ORAC - please look
Here we go. First offense* and he blew over a 0.150.
* Inferences are left as an exercise for the reader.
James @46: First, the screening frequency for the different age groups is a bit odd. Currently in the US older women are screened *more* often than younger women.
But far more to the point, this study says *nothing* about women who are known to carry BRCA1 or BRCA2. women with these specific gene mutations are know to have different (much higher) risks of breast and ovarian cancer than the general population. Therefore the conclusions of this study (of the general population) are not applicable to women who carry BRCA1/2.
Also, knowing about the BRCA1/2 genes doesn't say anything about the possibility of spontaneous regression of other cancers. Yes, the immune system is constantly working to get rid of cells that have gone off. But the evidence clearly shows that for women with the BRCA1/2 mutations, this doesn't work nearly as well as it does in women who don't carry these mutations. So it doesn't matter if sometimes tumors just go away by themselves if we know (we have mountains of evidence to show) that for people with these mutations, the risk of cancer is so much higher.
It's not like there is only one cause of cancer. We are talking about something very specific, that can't be generalized to the whole population.
Which BAC falls under Fla. Stat. ch. 316.193(4) and all that follows. The terms of the license suspension are in chapter 322.
Oh, but "Pretrial Disclosure Regarding App for Indigent Status Filed" apparently means that he tried to obtain a public defender.
Oh, Jeezums, he's pled not guilty and wants a jury trial. This is terrific.
No mullett? I'm disappointed.
He seems to have a good criminal defense lawyer, though. As-good-as-baseless speculation: he wants to cop to a non-DUI charge.
The thing about the Lancet study is that it covered 1986 to 1990. How good was the screening then for cancer? What one person saw, another may not have seen 4 years later.
The study isn't BS. It's James' interpretation of the study that is BS, as is his attempt to shoehorn it into the discussion of BRCA1 mutations as though it had any relevance whatsoever.
I've written about overdiagnosis on many occasions. For some background, see:
http://scienceblogs.com/insolence/2009/11/10/rethinking-cancer-screenin…
http://scienceblogs.com/insolence/2008/12/01/the-spontaneous-regression…
http://scienceblogs.com/insolence/2009/07/20/overdiagnosis-of-breast-ca…
http://scienceblogs.com/insolence/2010/06/16/cancer-overdiagnosis-and-o…
http://scienceblogs.com/insolence/2014/02/17/the-canadian-breast-screen…
http://scienceblogs.com/insolence/2009/12/14/how-not-to-protect-your-me…
There are quite a few other posts I've done on this issue. The study cited by James is of a piece with an evolving view that mammographic screening leads to overdiagnosis. What we argue about is just how much overdiagnosis.
he tried to obtain a public defender.
Online grifter pleads poverty? No-one could have expected that.
It would be very wrong to go over to Greenmedinfo and ask for positive-thinking / epigenetic tricks for reducing blood-alcohol in a hurry.
Maybe it wasn't alcohol at all but an herbal product designed to assist you in escaping the physical emcumbrances of everyday life so your spirit can SOAR unimpeded.
PLUS he weighs absolutely nothing for an adult man.
-btw- some woo-meisters I survey loathe demon alcohol because it destroys millions of brain cells per drink.
Although that doesn't explain their own cognitive issues.
James @#35: From 0 to CONSPIRACY!!1 in three posts! I think that might be some kinda record!
"FINDINGS:
Before the age-matched controls were invited to be screened at the end of their follow-up period, the 4-year cumulative incidence of invasive breast cancer was significantly higher in the screened group (982 per 100,000) than it was in the control group (658 per 100,000) (relative risk [RR] 1·49, 95% CI 1·41-1·58). Even after prevalence screening in the control group, the screened group had higher 6-year cumulative incidence of invasive breast cancer (1443 per 100,000 vs 1269 per 100,000; RR 1·14, 1·10-1·18)."
So after six years one tumor in six had regressed and no one knows how to determine which will regress and which will do their best to kill the patient.
Orac has written about this, you know. It's not news to him or regular readers.
GMI requires "membership" in order to "unlock" the "print-friendly view." If he's rolling in the vault like a common Scrooge McDuck, it's not reflected in the domicile.
Denice, #60
I saw that too! 120 lbs at 5' 9"!
Mon Dieu.
And he's "white". Some kind of complex about his ethnic origins?
So I suppose the next time Sayer whips up an organic green kale and kava smoothie for himself he'll leave out the 5 shots of non-GMO, gluten-free vodka.
I am making an appointment for my overdue mammogram.
Of course now JP will call me an a__hole for not having it sooner.
Wish they handed out weed when I go.
Although the URL looked clear, I see that that link actually requires a session cookie (i.e., it doesn't work).* To find the docket, go here, choose "Criminal & Traffic Case Records," and enter case number 15CT500965.
The more complete charge description in the docket – as opposed to the sheriff's entry – leaves open the possibility that he wasn't that drunk, just above the limit and transporting a minor late at night on the 15th.
* Another sign that something is off in my antakarana: some public-radio idiots just played – without mockery – a recording of one Alicia Keys quoting "Frederick Nietsche."
^ "Nietzsche," dammit. Now I'm going be lumped in with the execrable Peter Sagal.
Um, no. That doesn't make any more sense than any of the rest of the nonsense you've been blathering on about.
According to Fearless Parent, Ji has 2 children.
To clarify from the perspective of a practicing medical oncologist... the study that Orac is discussing applies to patients that already have a biopsy proven cancer. There has been concern that patients who are BRCA carriers (particularly BRCA1) with confirmed cancer have a worse prognosis than patients with confirmed cancer who are not BRCA carriers. The meta-analysis suggests that the prognosis for these patients are likely similar when treated with appropriate combinations of definitive and adjuvant therapy. BRCA1 carriers in particular are more likely to develop triple negative breast cancers that have a worse prognosis when compared to the other major subsets of breast cancer (e.g. HER2 and the luminal A/B hormone receptor positive subsets). Therefore, anecdotally, BRCA1 carrying patients certainly strike the practicing medical oncologist as having a worse prognosis due to the prevalence of triple negative tumors. Everyone remembers the 30 year old patient who comes in with a huge inflammatory cancer and is dead within the year...
This study does not in any way suggest that the risk for breast cancer and ovarian cancer in BRCA1 carriers is not the respective ~80% and ~40% risks that multiple studies have demonstrated. It most definitely does not suggest that these patients don't need aggressive treatment when diagnosed with a cancer. Nor does it in any way suggest that prophylactic surgery is overkill, and not a solid and appropriate recommendation in patients who carry the BRCA1 mutation.
Hope that helps... and hope I'm not being too redundant.
In regards to the Lancet study that James posted above, it is true that there is now some evidence that low grade ER/PR+ tumors in the elderly may not progress in some patients, and that they may actually regress in some and may not always require treatment. This is a situation akin to the numerous low grade prostate cancers we see in elderly men. Unfortunately, we have no way to decide who may or may not benefit from treatment. Triple negative tumors in younger patients are not something that you want to leave untreated, as they grow quickly, spread quickly, and cause death quickly.
All the more reason for him not to have been going 105 in a 70 mph zone while above the legal limit.
(Enter instead case 15TR017786.)
Jeebus - reminds me of my mom.
You heard it here first.
It'd be entertaining if anyone picked it up, but the deeply discounted flat-cut corned beef at the end of the rainbow is neither more nor less than bumptious legal threats.
I presume that's just what it says on his driver's license. There was no weigh-in the last time I had to renew mine.
That would be about a 28-inch waist at that height if my high-school memory suffices. I doubt that a 42-year-old is really that scrawny, but it wouldn't excuse being a "cheap date" in any event.
@ Surgeon in Arms #51
Journeying to the Moon and having a chat with the locals sounds like fun, but I'm not sure I would let an extraterrestrial being mess-up with my genes.
@ Surgeon in Arms #51, Helianthus#77 - in fact the linked site refers to selenium - which at least is terrestially available, although perhaps equally quacky.
I can vouch for selenium sulphide shampoo being very effective against dandruff, although you smell of rotten eggs for some time afterwards.
...Dach does refer to a sciency-looking study which seems to indicate that selenium may have some beneficial effect:
http://www.ncbi.nlm.nih.gov/pubmed/20063075
Whether that justifies a recommendation for it like he promotes is another matter.
The development of 3D screening should help on the Tech part of the overdiagnosis problem.
Re#76. Hate to kind of get off the subject of the original post, but I finally looked at your links. Whoo hooo!
Anyway, any idea what kind of a car he was driving. Not that 105mph is horribly fast. Just wondering if his business is doing well enough to afford a Mercedes?
Narad has indicated that, judging by his digs, he's not really rolling in dough or anything, so I doubt it was a Mercedes. In any case, 105 mph is well within the reach of, say, a 1999 Oldsmobile*, or most cars, really.
*The particular car I'm thinking of no longer exists. Nice job, mom.
Al Gore's kid was arrested for going 100 mph in a Prius; that's apparently near the top speed.
http://www.slate.com/articles/news_and_politics/explainer/2007/07/yesa_…
I'm more into MPG than MPH, myself.
I'm an ordinary 57-year-old female--not a BRCA1 carrier and not someone who has ever been diagnosed with any cancer. It's beginning to bug me that my family practitioners have both told me more about the possibility of spontaneous regression of cancers generally than I ever remember hearing before, and when I've asked about genetic testing because of an unknown breast cancer type in a close relative, I was actively discouraged. What gives? They are also starting to harp a bit on overuse of mammograms and overdiagnosis in general. I'm wondering whether there's some pushback by primary care docs because of these various controversies. They seem much more casual about many issues related to all this now. Is it that female patients my age are overreacting and they are getting tired of calming people down who may have no unusual risks? Confused....
I would offer that they are concerned that you fit more into the risks associated from an improper intervention(s) from a false alarm than that of developing cancer itself.
It's a valid concern.
The guidelines I have offer imaging every 1-2 years.
I think the 3D technologies are really going to help in differentiating normal from abnormal tissues. With only 2D, normal tissue can stack on each other and look like a problem area, when indeed it may not be.
Narad - I rather like Peter Sagal.
Hey Orac, Mike Adams has said the Germanwings crash was caused by psychiatric meds. http://www.donotlink.com/www.naturalnews.com/049137_Germanwings_depress…
@ Nianbo
T'was to be expected. Psy meds is one of Mike's pet peeves.
Mikey, like many other woo-meisters, believes that anti-depressants cause depression and anti-psychotics cause psychosis. Meds cause mental illness. They have an axe to grind against psychologists, too.
I wonder why?
For even more of Mad Mike, see Thursday's 'Wheel of Intolerance' post wherein he discusses the "outrageous bigotry of the left" who are intolerant of Christians, white men, southerners ( US only), gun owners, soldiers, veterans, pro-life advocates, home schoolers, small business owners, anti-vaxxers and libertarians like him. Poor Mikey!
I am especially taken by he illustration of a woman ( seen spinning the wheel) .I wonder who SHE is supposed to be?
-btw- I like her outfit and would definitely wear it.
I dunno - I've wondered about what you're insinuating when it comes to, say, L Ron Hubbard*, but even there, I think he was more of a genius level sociopath if anything, and he resented psychiatry because it was a competitor with his auditing scheme.
I mean, it takes certain degree of self-awareness and tendency to introspection to seek out the services of a psychologist, and I don't see much evidence of any of that in people like Mike Adams. The whole anti-psych-meds thing seems to me just another aspect of the anti-medicine attitude of the woo-meisters in general.
Psych meds do get singled out as being especially bad in a lot of alternative communities; I can't count how many rants I've heard from my beloved counter-cultural types about kids being "doped" with ADHD, or SSRIs being pushed on Americans to make us all "numb" and blind us to the destructive and depressing nature inherent in the capitalist-military-industrial system we live in.
I mean, there certainly are legitimate criticisms to be made of psychiatry. I do think SSRIs are over-prescribed, and probably things like Ritalin too - though I don't know as much about ADHD issues - but what I find particularly worrisome is the near explosion in the use of atypical anti-psychotics for all kinds of off-label indications, anxiety, depression, PTSD, dementia, you name it. I mean, these are heavy duty drugs with serious side effects, and I really don't see any justification for their use outside of treating actual psychotic disorders.
*I believe I've seen some evidence that Mike Adams was a Scientologist back in the day, actually, or at least associated closely with them, which might explain part of his anti-psychiatry BS as well.
The thing that cracks me up about Mikey using a cartoon of Rachel Maddow as an example of this "liberal bigotry," which supposedly includes bigotry against veterans, is that Maddow describes herself as a "national security liberal" and is in fact very concerned about all kinds of veterans' issues. Rather more than Mike Adams is, I imagine.
@ JP:
Woo-meisters - esp Null- promote *specific* products ( and diets) to ameliorate symptoms that most people would identify as being associated with mental illness ( see 'Mellow Fellow') or LD/ ASD. Mike isn't quite so clear about the uses of diverse vitamins, minerals and herbals he markets. It's interesting to look at any of these charlatans' web stores and see their wares. (and lately, boner pills are big/ and women's formularies)
Orthomolecular psychiatry, upon which GN's approach is based, purports that niacin and other supplements are vastly superior to meds. There are also recommendations involving minerals ( magnesium esp) and use of herbs like St John's Wort , Valerian et al.
Orac did discuss Mikey's possible relationship to Scientology.
A fabulous minion sent a film clip of "Mike" singing.
And yes, I included that Liberal cartoon character just for you
JP may be thinking of the following RI article concerning Mike Adams and Scientology:
http://scienceblogs.com/insolence/2011/06/23/scientology-and-mike-adams…
http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews…
^^I'd call that justification for the potential use of atypicals as adjunctive therapy for depression, PTSD, and OCD and as a primary therapy for dementia. And since Seroquel is probably a safer treatment for anxiety than a benzo would be, that too.
And they're mostly prescribed at what would be subtherapeutic doses for psychosis when used off-label anyway. It's not like they have fixed, heavy-duty properties.
I mean, as with most psychotropics,a lot of people don't like taking them. But that's not always a problem. And assuming it isn't, what makes them unjustified?
Regarding dementia, I notice that the review you linked to states that they're effective in reducing behavioral symptoms of dementia. One of the things that gives me pause about the use of these drugs is that they seem to be used, more often than not, as chemical restraints in settings like nursing homes. It's true that a lot of people don't like taking them, and they usually have reasons for that - they're sedating, they feel "blunting," you tend to gain weight on them, etc. So I think if somebody doesn't want to take them, that's valid, but there's a pretty large power differential going on in places like nursing homes, and I imagine there might well be plenty of people who don't want to be taking those mediations but for various reasons aren't exactly having their voices heard about it.
It's true that there are big risks to benzos, but I can't help but see SSRIs as a better choice there, given that they're quite effective as anti-axiolytics and have much lighter side effect profiles. It's true that they can take a while to kick in - several friends of mine with anxiety disorders started on SSRIs and were given one PRN script for a benzo to use until the SSRI kicked in.
I mean, antipsychotics are, including in the review you linked to, associated with increased death rates in the elderly, increased risk of cerebrovascular accidents, weight gain, definitely sedation.
The "Remaining Issues" section also leaves one feeling that actual evidence about dosage, length of treatment, etc., is thin to non-existent.
^ Bah, typos. The review you linked to does seem to indicate, in any case, that any efficacy for off-label uses of atypicals is limited:
I mean, if supplementing with an antipsychotic can help somebody with severe, treatment resistant depression, or intractable PTSD symptoms, and they go into it knowing all the risks involved, and they feel like the decision is theirs and not somebody else's, and the evidence shows that it can help, I'm all for it. But I feel a little bit weird about all the direct-to-consumer advertising I've been seeing in magazines and suchlike over the past few years for drugs like Abilify which make them seem like mild antidepressants and nothing more. I mean, I'm kind of weirded out by direct-to-consumer advertising of pharmaceuticals in general, for that matter. Yay, America. (And New Zealand, I think?)
@James #46
Perhaps you would be more comfortable at dailykos.com where they actively promote the wild eyed enthusiast who runs around screaming and waving a paper he can not even begin to understand.
Orac properly identified you as obtuse. This characteristic is valuable in the activist who need only be utterly convinced of the righteousness in his cause, the accuracy of his beliefs being secondary if not irrelevant. We in the Science community have different standards and value different characteristics.
@Susan K #30
Christiane Northrup, the astrologist?
http://www.drnorthrup.com/astrology-doctor-are-you-kidding/