Dr. Lorne Brandes
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June 28, 2016

6/28/2016

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An important study just published in the Annals of Internal Medicine has found no evidence that receiving a blood transfusion from donors with a neurodegenerative disease, such as Alzheimer's or Parkinson's, increases the risk for neurodegenerative disease in the recipient. This finding may go some distance in allaying concerns that these diseases can be spread from person to person. Underlying this worry has been scientific evidence that abnormal (misfolded) proteins, similar to prions, are the likely cause of many neurodegenerative disorders that spread through the central nervous system over time.
That said, did you know that prion-like proteins, implicated in dementia, also appear to be vital for the formation and retention of normal memory? Read more in this re-posted CTV.ca/health blog I wrote in 2012.
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​The narrow line between forming memories and losing them

 by Dr. Lorne Brandes   Jul. 11, 2012 

Judging by the number of “recommenders” on the Facebook link, a lot of readers were interested in last week’s blog, Targeting iron in Parkinson’s Disease (PD). Apart from the role that iron may play in neurodegenerative diseases, perhaps what fascinated most people is the likelihood that a prion-like protein, called alpha-synuclein , may initiate Parkinson’s and then spread it from one brain area to another.
To review,  prions (derived from “protein infection”) can exist in two forms, each exhibiting a distinct shape and behavior:
  • in their normal (or “recessive”) form, prions have a corkscrew shape, called an alpha-helix; recessive prions are manufactured by our genes, are the most common type, and reside harmlessly in cells.
  • however, when, for a variety of reasons, several recessive prions cluster together to form oligomers [from the Greek “oligo”, meaning “a few”], their shape changes into a misfolded (“dominant”) protein that resembles a pleated sheet.
With the change in shape comes a change in character: unlike their recessive cousins, dominant prions self-replicate, using themselves as a template to form new dominant prions. For poorly-understood reasons, they can also behave as rogues, killing brain cells as they spread, like an infection, through the nervous system.
Now, with the identification of neurotoxic prion-like proteins, such as alpha-synuclein in PD, and beta-amyloid and tau in Alzheimer’s dementia (AD), scientists are openly discussing the hypothesis that many common human neurodegenerative diseases are “ prion disorders ”, not unlike mad cow disease (BSE) in cattle and scrapie in sheep.
But trumping even that possibility is the amazing discovery that those very same dominant prion oligomers are essential for the formation of long-term memory!
The earliest indication that this might be so surfaced over a decade ago in the Columbia University laboratory of Dr. Eric Kandel, who shared the 2000 Nobel Prize in Medicine for his pioneering work in brain signaling (more specifically, how the brain responds to environmental stimuli and, in the process, forms and retains memories).
While experimenting on the sea slug (Aplysia), a model of nerve function developed by Kandel, Dr. Kausic Si, a postdoctoral fellow, discovered that a vital protein, called CPEB , continuously replenished other proteins that maintain and enhance the function of new nerve endings, or synapses , that sprout in response to operant conditioning (learning), or to repeated exposure to serotonin , a brain neurotransmitter. 
That of itself was an important new discovery. Yet, both Si and Kandel knew that the life of most proteins is short, usually hours. How was CPEB, itself a protein, able to persist and sustain the new nerve endings for long periods of time, perhaps for the life of the sea slug?
After analyzing its structure, Si came up with a startling finding. Kandel describes what happened next in his must-read book, “ In Search of Memory ”:
“I remember it was a beautiful New York afternoon in the spring of 2001, the bright sunlight rippling off the Hudson River outside my office windows, when Kausik walked into my office and asked, ‘What would you say if I told you that CPEB has prion-like properties?’
“A wild idea! But if true, it could explain how long-term memory is maintained in synapses… Clearly, a self-perpetuating molecule could remain at a synapse indefinitely, regulating the local protein synthesis needed to maintain newly grown synaptic terminals.”
Further experiments conducted in yeast cells by Si cemented the observation; CPEB, did indeed have dominant prion-like properties.
But it was one thing to show that CPEB resembled a dominant prion and another to establish conclusively that this likeness was essential to forming and maintaining long-term memory.
That proof came earlier this year. In a study published in Cell, scientists led by Dr. Si, now at the Stowers Institute for Medical Research in Kansas City, showed that, like CPEB in the sea slug, Orb2, a similar nerve cell protein in fruit flies, looks and behaves like a dominant prion oligomer.
Once that was confirmed, Si and his colleagues carried out two operant conditioning experiments in male fruit flies: learning to avoid a female mated to another male; and learning to associate a specific odour with a food (sugar) reward. The result? Orb2 conferred long-term avoidance and association memory (lasting beyond 48 hours) in normal fruit flies. In contrast, mutant fruit flies that carried only a recessive (non-replicating) form of Orb2, retained what they had learned for 24 hours and then completely forgot when retested at 48 hours.
"Self-sustaining populations of [dominant prion oligomers] located at synapses may be the key to the long-term….changes that underlie memory; in fact, our finding hints that oligomers play a wider role in the brain than has been thought," Dr. Si told Science Daily.
He and his team now plan to see how long Orb2 must be present to keep a memory alive. "We suspect that [it] need[s] to be continuously present, because [it is] self-sustaining in a way that [recessive] Orb2 [in mutant fruit flies] is not," Si commented .
As Dr. Kandel notes in his book : “…basic science can be like a good mystery novel with surprising twists: some new, astonishing process lurks in an undiscovered corner of life and is later found to have wide significance. This particular finding [that CPEB is prion-like] was unusual in that the molecular processes underlying a group of strange brain diseases are now seen also to underlie long-term memory, a fundamental aspect of healthy brain function. Usually, basic biology contributes to our understanding of disease states, not vice versa.”
By now, it should be apparent that there is a fine line between forming and losing memory: in normal circumstances, dominant prions giveth; in pathological circumstances, they taketh away.
An answer to the riddle of what goes awry to make them “taketh away” could allow us to prevent many, if not all, neurodegenerative diseases.
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 June 27, 2016

6/27/2016

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Thanks to oncologists at Houston's MD Anderson Cancer Center, we now know how, and when, to treat breast cancer in pregnancy. Here is a re-posting of a blog on the subject that I wrote for CTV.ca/health in 2010. The information remains pertinent in 2016.
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Treating breast cancer in pregnancy: Good news for mother and child
by Dr. Lorne Brandes   October 22, 2010 

​For decades, it was every oncologist’s nightmare: a pregnant woman diagnosed with rapidly growing breast cancer. What to do? Terminate the pregnancy? Wait until delivery before starting chemotherapy? Treat immediately but reduce the dose of chemotherapy in an attempt to protect the fetus? Until recently, nobody knew the answers to these very difficult questions.
Now, thanks to pioneering studies carried out at Houston’s prestigious University of Texas MD Anderson Cancer Center, we do. Not only has a clear roadmap emerged to help us safely navigate this minefield, but we can also confidently offer a much more encouraging prognosis to the pregnant patient and her unborn baby. Here is the story.
Starting in 1992, MD Anderson oncologists began treating pregnant women with standard (full) doses of three widely-used breast cancer drugs in a regimen called "FAC" (5-fluorouracil, doxorubicin [Adriamycin] and cyclophosphamide). To minimize harm to the fetus, they waited until after the first trimester to begin the chemotherapy. After delivery, radiation treatment, and additional drugs, such as tamoxifen and Herceptin, were administered when indicated.
Close follow-up was provided over the ensuing years to monitor the mothers for any signs of recurrence and to assess the health and development of the children.
The first encouraging news emerged in a 2006 paper that described the MD Anderson team’s results in the first 57 women and their offspring. Not only was the short-term outcome better than expected, with 44 of 57 (77%) women alive and cancer-free after 3 years of follow-up, 97% of the children were reported to have "normal development compared to siblings or other children." Only three had congenital birth defects: one with Down syndrome, one with a club foot, and one with a relatively common and treatable abnormality (called "reflux") of the ureters that drain urine from the kidneys into the bladder.
That wasn’t all we learned from the study. Prior to that time, it had been generally believed that breast cancer in pregnant women grows and spreads rapidly because of high levels of maternal estrogen; this hormone drives tumour growth in two-thirds of non-pregnant women with the disease. However, meticulous analysis of the pregnant women’s tumours revealed that they were estrogen-driven in only 30% of cases, while 70% were "triple-negative" high grade cancers that typically grow independent of estrogen and carry a poorer than average prognosis. Suddenly, we had an alternative explanation for the aggressive behaviour of breast cancer in pregnant women!
But the surprises didn’t end there. At the recent 2010 Breast Cancer Symposium, the MD Anderson’s Dr. Jennifer Litton reported that 75 pregnant women have now been treated and followed for an average of five years. Given the aggressive nature of breast cancer in pregnancy, their disease-free survival rate remains remarkably high at 74%.
However, what really caught everyone’s attention was how that result compared to the outcome her group obtained using the same "FAC" chemotherapy treatment in 150 non-pregnant women with breast cancer who were closely matched for age, year of diagnosis, and stage of disease. As opposed to pregnant women, non-pregnant women had a significantly lower five-year disease-free survival rate of 56%!
How to explain the difference? According to Dr. Litton, "We are not sure why our pregnant breast cancer patients had better outcomes than those who were not…is there something biological in the milieu of pregnancy that changes the response to chemotherapy?" Finding that answer will be her group’s "research priority", she said.
As an oncologist who treats this disease on a daily basis, I wish her and her colleagues every continuing success. While much longer follow-up will be required to determine the ultimate cancer-free survival of the mothers, as well as any long-term effects of in utero exposure to chemotherapy in their children, thanks to the MD Anderson researchers we are already light years ahead in our ability to advise, reassure, and treat pregnant women with breast cancer.
 

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June 22, 2016

6/22/2016

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With the recent death of Muhammad Ali from complications of Parkinson's Disease (PD), new attention has turned to the causes and treatment of this all-too-common neurodegenerative disorder. As a result, I am re-posting a blog I wrote for CTV.ca/health in 2012 that examined the role of iron buildup in the brain that may promote the formation of an abnormal prion-like protein, called alpha-synuclein, that many neuroscientists now believe to be at the root of PD and may explain the progressive spread of this disease throughout the brain over time. The blog garnered much interest and many citations on other websites. Here it is.
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Targeting iron in Parkinson’s Disease
by Dr. Lorne Brandes  Jul. 4, 2012 

There are some exciting findings afoot to suggest that too much iron in brain tissue is a common finding in neurodegenerative diseases, and that removing it with certain drugs, called chelators, may significantly improve symptoms.
But to help you understand this, I first need to review some additional scientific information.
In a recent blog on Alzheimer’s Disease (AD), I reported on a misfolded protein, called tau. In its normal form, tau has a corkscrew appearance (called an “alpha-helix”). However, when too much tau is made by cells, multiple tau molecules stick together (aggregate). In the process, tau changes shape (misfolds), becoming a pleated structure (called “beta sheets”) that is toxic to nerve cells.
Of great interest, pleated tau structurally resembles a prion, the infectious agent that is best known for causing mad cow disease (BSE, or bovine spongiform encephalopathy). BSE can be transmitted to humans who eat prion-infected meat (the human form of BSE is Creutzfeldt-Jakob disease, a rapidly-progressive neurodegenerative disorder).
Even if tau looks like a prion, does it behave like one ? It appears that it does: researchers have discovered in mice that, similar to the progression of AD in humans, tau first accumulates in a memory area of the brain called the entorhinal cortex and then spreads along nerve networks “like an infection” to progressively involve other memory centres.
How does pleated tau spread? Scientists believe that it uses itself as a template to form replicas that leave the cell and move from nerve to nerve. That said, unlike BSE, so far there is no evidence to suggest that tau can survive outside the nerve cells of the human brain or be transmitted from one person to another.
Yet, transmissible or not, the prion-like structure and “contagious behaviour” of tau has suddenly become a hot topic among neuroscientists who quickly point to another misfolded (pleated) protein, called alpha (α)-synuclein, a neurotoxin that is strongly linked to Parkinson’s Disease (PD).
Under the microscope, nerve cells affected by PD contain rounded inclusions, called Lewy bodies (named after their discoverer, Dr. Frederic Lewy), that are rich in alpha-synuclein. Pathologists have also identified Lewy bodies in human embryonic stem cells that were implanted into brains years earlier in studies to treat PD.
Noting that these transplanted donor cells must have become “infected” with alpha-synuclein from the recipients’ brains, Dr. Stanley Prusiner, who won the 1997 Nobel Prize for discovering the prion, recently suggested that, indeed, PD may be “a prion disorder”!
Is he overstating the case?
Consider this: we now have evidence that, even before PD affects the brain, it starts in the sympathetic nerve fibres that control bowel function. Researchers have found biopsy evidence of alpha-synuclein in gut tissue up to five years before typical brain-related symptoms of tremor and muscle rigidity occur. Indeed, chronic constipation, likely caused by alpha-synuclein damage to sympathetic nerve cells, may be the earliest symptom of PD.
Over time, the disease appears in (spreads to?) the brain, initially involving the brain stem, and then moving to an area of dark-staining brain tissue, called the substantia nigra (SN).
The cells of the SN produce a neurotransmitter chemical, called dopamine, that is vital to normal brain function. When approximately 80% of the dopamine-producing cells die from the effects of alpha-synuclein, the typical tremor and/or rigidity symptoms of PD appear. 
Although a drug called L-dopa can relieve these distressing symptoms by replenishing the lost dopamine, it is by no means a cure. Nerve cells continue to wither from alpha-synuclein as the disease spreads to other areas of the brain and spinal cord.
Now (and thank you for being patient) here is where iron comes into the picture: in addition to alpha-synuclein, Lewy bodies contain abundant iron. In addition, a heavy buildup of iron is found specifically in brain areas affected by PD.
Perhaps most important of all, new studies show that iron not only regulates cell production of alpha-synuclein, but promotes its misfolding into the neurotoxic prion-like pleated form!
Suddenly, many researchers are suggesting that removing the buildup of iron in brain tissue might be one way to control the production (and, possibly, misfolding) of alpha-synuclein, thereby slowing or halting the progression of PD and other neurodegenerative diseases.
Indeed, early clinical trials of an FDA-approved oral iron chelator, called deferiprone, have shown promise to decrease brain iron and relieve symptoms in a related neurodegenerative disease called Friedreich’s Ataxia (spinocerebellar degeneration).
Could deferiprone also benefit patients with PD? Dr. David Dexter of London’s Imperial College hopes to find out. He is the principal investigator of a phase 2 trial involving 36 patients; the study, which opened in February, has already accrued close to half of the required subjects.
If the results look promising, phase 3 studies in PD, as well as new trials in other neurodegenerative diseases where brain iron levels are high, such as Huntington’s  Disease  and Lewy Body Dementia will almost certainly follow.
But as always, there is a note of caution. Even if iron chelation therapy helps patient with PD, it is unlikely to be curative. Nerve cells that have already succumbed will not return. Alpha-synuclein that is already misfolded might continue to act as a template, spreading the disease. Dopamine will still need to be buttressed by drugs like L-dopa. Moreover, deferiprone has some potentially serious side effects that must be weighed against any potential benefits.
Nonetheless, the tantalizing prospect that, through its effects on alpha-synuclein, iron may play a major role in more than one neurodegenerative disease process, and that chelation therapy could be an effective antidote, is worth everyone’s attention
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June 21, 2016

6/21/2016

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Hardly a month goes by without new research findings that may ultimately change our approach to treating breast cancer. Just yesterday, researchers revealed that the cells giving rise to hereditary breast cancer resulting from the BRCA1 mutation can be targeted with an anti-osteoporosis drug called denosumab. This raises the possibility that this monoclonal antibody might actually prevent breast cancer in these women and save them from having to undergo prophylactic mastectomies. However, this approach, although exciting and on solid scientific ground, will need to be carefully assessed in properly-designed clinical trials to know whether it works and is safe over the long term. If so, it will almost certainly become the new approach in this select group of women with a very high lifetime risk of developing breast cancer.
The BRCA1 story reminds me of an important study, called METABRIC, published in 2012, that found there were ten different types of breast cancer. I reported on it in my CTV.ca/health blog, re-posted below.

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I
mproving the treatment of breast cancer: A tale of 10 diseases
by Dr. Lorne Brandes  April 23, 2012 
 
Having treated breast cancer for four decades, I can attest to the progressive improvement in outcome in women diagnosed with early-stage disease. Multi-pronged advances in chemotherapy, radiation and hormonal therapy, aided by earlier detection through regular screening mammograms, have increased the five-year survival rate from 71% when I began practice in the early 1970’s, to 90% in 2012.
Yet, despite this impressive gain, and beyond what the statistics tell us, I am always humbled by our inability to predict the outcome for any specific patient. I remember the faces of those I thought would do well but didn’t, and, conversely, of those I thought might fare poorly but did well.
The reason? Despite the fact that two women may present with breast cancers of identical clinical stage (the degree of spread) and pathological grade (the degree of malignancy under the microscope), their tumours may have radically different biological characteristics and sensitivity to treatment.
For example, approximately two-thirds of malignant breast tumours contain receptors for the female hormones estrogen and/or progesterone. A high content of both hormone receptors generally indicates a better prognosis; recurrence often can be prevented by oral antiestrogen drugs such as tamoxifen or the newer class of aromatase inhibitors. On the other hand, the one-third of tumours that lack hormone receptors are less predictable in their behaviour; nonetheless, chemotherapy significantly improves the outcome in such cases.
Twenty per cent of breast cancers produce high levels of a receptor protein called HER2 . These tumours usually lack estrogen and progesterone receptors, tend to be very aggressive ( high grade) and are more likely to spread (metastasize). However, in recent years, their recurrence rate has been cut in half using chemotherapy in combination with the HER2-targeting drug, Herceptin.
Tumours that lack estrogen, progesterone and HER2 receptors are called triple-negative; they also tend to be high grade. Unfortunately, they often recur despite aggressive chemotherapy and radiation, but those that do not come back within 2 to 3 years after treatment are usually cured.
While tailoring breast cancer therapy according to stage, grade, and receptor status has greatly improved overall survival, choosing the best treatment in each case, based on an accurate prediction of individual outcome, has remained elusive.
But now, that situation is about to change dramatically.
As a result of a landmark study just published online in Nature, we have been given a whole new roadmap of the biology of breast cancer; with it comes the ability to more accurately predict the behaviour of individual tumours.
This breakthrough was made by a consortium (known by the acronym METABRIC) of Canadian- and U.K-based. cancer researchers led by Drs. Samuel Aparicio of Vancouver’s British Columbia Cancer Centre and Carlos Caldas of the Cambridge Research Institute.
By analyzing the DNA in almost 2,000 breast cancer tumours, the scientists discovered that individual tumours contain one of 10 different “clusters” of altered (abnormal) genes. Some of the genes (like the one that produces the HER2 protein) were predictable, but several others had no previously known link to breast cancer.
The group’s conclusion? Breast cancer is not one, but 10 different diseases! Each subtype exhibits unique genetic (and, therefore, biological) characteristics.
But there is more. Because the outcome of treatment was documented in every tumour donor, the prognosis for each of the 10 subtypes of breast cancer is now known!
As one example, tumours with altered “cluster 4” genes, including some high-grade triple-negative cancers, were observed, surprisingly, to be associated with a good prognosis. Intriguingly, cluster 4 alterations do not involve cancer genes; rather, they are associated with immune system genes. This might explain why a rare form of high-grade triple-negative breast cancer, called “medullary”, has a better than average prognosis: medullary breast cancers are typically infiltrated by millions of “killer” immune cells, called CD8 lymphocytes.
These findings raise the possibility that “cluster 4” immune system genes could be harnessed to improve the outcome in other, less responsive forms of breast cancer.
To illustrate, although estrogen receptor-positive breast cancers generally have a good prognosis, the METABRIC study identified two exceptions: an estrogen receptor-positive subtype, containing “cluster 2” gene abnormalities on chromosome 11, responds poorly to blocking estrogen; a second estrogen receptor-positive subtype, containing “cluster 5” abnormalities on chromosome 17 (the HER2 gene), has an extremely poor prognosis despite the use of chemotherapy, Herceptin and antiestrogens.
Could immune stimulation change the poor outcome in these two instances? Evidence that this could be so comes from recent studies showing that chemotherapy given prior to surgery can eradicate breast cancer and significantly increase survival when CD8 cells infiltrate tumours in high numbers.
Commenting on the importance of the METABRIC study, leading British genetics researcher, Professor Charles Swanton, described the new results as an “extraordinary” finding that took our understanding of breast cancer “to the next level”. These findings are “likely to have important implications for clinical trial design in breast cancer and will prime researchers worldwide to define new approaches to treat each subgroup,” he said.
Lead METABRIC researcher, Carlos Caldas, added, “I want to stress, this…wouldn’t have been possible without the breast cancer patients who donated their samples and agreed to take part in the study. None of this would have happened without them, and I’m so grateful for their participation.”
My take? While the full impact of these findings will take years to realize, they are truly revolutionary, certain to ultimately result in more effective breast cancer treatment and improved survival.
 
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June 20, 2016

6/20/2016

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One of the most common problems that afflict modern society is acid reflux, commonly called heartburn. This symptom is usually caused by the regurgitation of acid from the stomach into the esophagus. Not only is it an unpleasant sensation, but if left untreated it can sometimes lead to esophageal cancer. While H2 acid blockers, such as ranitidine, and the newer proton pump inhibitors, such as omeprazole, are often effective, some people do not get relief from them. While not widely known, honey can be a very effective remedy, as discussed in a CTV.ca/health blog I originally posted in 2010.
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Curing heartburn when pills don’t work: A honey of a suggestion

by Dr. Lorne Brandes  December 8, 2010
 
"I feel fine except for my chronic heartburn," a young woman told me a few months ago during a follow-up visit. Happily, with tests indicating that her breast cancer remained in remission, we had the luxury of focusing that day on her dyspepsia.
Bad heartburn symptoms had started during a pregnancy 10 years earlier (not uncommon) but persisted after delivery. She saw a specialist, had the usual tests for ulcers and hiatus hernia (none found), was told she had "hyperacidity" and was prescribed a series of antacids; none worked. "Now my doctor has me on Pariet [a proton pump inhibitor]; even that doesn’t give me good relief of my symptoms," she lamented.
Desperate for any alternative suggestion, I gave her one. "I want you to try a tablespoon of liquid honey before breakfast and at bed time every day. If your symptoms go away within a week or two, try stopping the Pariet, and stay on the honey until I see you in three months," I instructed. She promised she would try my "home remedy".
She returned for her next visit with a big smile on her face. "It’s unbelievable," she blurted out before I could pop the question. "The honey completely stopped my heartburn within two weeks. I stopped the Pariet and have not needed it since. This is the first time in ten years I don’t feel as though there is a fire in my stomach." Even I was impressed!
So, you may ask, how did I know to tell her about honey? It all started two years ago when I received an e-mail from my youngest brother, Ken, a self-employed entrepreneur/businessman who is also one smart and very funny fellow. I kid you not, here is what he had to say:
"To: The family doc (Revised scene from The Graduate)
Me: I just want to say one word to you – just one word.
You: Yes, sir.
Me: Are you listening?
You: Yes, I am.
Me: HONEY.
You: What exactly do you mean?
Me: There’s a great future in HONEY. Think about it. Will you think about it?
You: Yes, I will
"For 60 years I have lived with the world’s most cantankerous stomach. I invented acid reflux when no one had ever heard those two words side by side….diagnosed "colicky" as a new-born, "nervous" stomach as an adolescent, "type A" in my 20’s, "occupational hazard" of being a retailer in my 30’s, "probably allergic" in my 40s-50s.
"There was always some doctor telling me my stomach was what my stomach was, and prescribing the usual antacids each and every decade… but they never worked for more than 30 minutes before the aching, burning discomfort started up again… that is the reason I have never been able to sleep more than 2 consecutive hours in my entire life on the planet. No sooner would I assume the prone position, and all would be quiet on the Western front, when a Vietnam war-era flame thrower would shoot a plume of burning gas straight up the old gullet… at least, that is how I always pictured what was going on internally.
"So I resigned myself to the fact that it would always be thus and life would have to go on. Years of experimenting with diet never achieved any lasting results, although I eliminated meat, anything sweet, milk, etc… but nothing worked… meditation didn’t work, yoga didn’t work. Anyway, as Darwin predicted, I acclimated to my constant "sleepus interruptus", adjusted to it and became inured to the constant discomfort of heartburn.
"[Now] fast forward to 30 days ago. For the last 3 months I had tried blender drinks for breakfast – a few ounces of water, 6 ounces lactose-free skim milk, [various fruits], 3 teaspoons of yogurt and a sprinkling of [natural grain cereal]….hit the liquefy button and wait a couple of minutes….anyway, as much as I am addicted to these "health" drinks they are murderous to my alimentary canal….I wake up in the morning with a mixture of bile and fruit concoction in the back of my throat, afraid to belch for the fact that it would spew out my mouth.
"Then one day… for whatever divine reason… I decided my concoction needed HONEY…. so I purchased some liquid Munro honey, made by Sunshine brand in Alvinston, Ontario.
"As I was making my morning drink last month I decided to just squirt some honey straight into my mouth (I have that luxury as a person who lives alone). As someone who has not had sweets for 45 years, it was quite satisfying… anyway, I added some to my drink and downed it and that was that… by mid afternoon, I noticed I didn’t have the usual regret for having eaten earlier in the day.
"I then ingested some more honey at dinner time and an hour before bed….I repeated this the next day and the next….to make this rather tedious story short, I have not had one episode of acid reflux, day or night in over 30 days… just like that... just like a miracle! For the first time in my life, I am never aware of my stomach or its contents….whatever microbe, bacteria, nematode or alien that had been lurking somewhere in my alimentary canal my entire life is now history.
"Now I sleep 6 hours straight. I can’t tell you the overall feeling of well being I have….and it is not a placebo effect….I have pushed the envelope, so to speak… I have never been able to eat past 6 or 7 pm without dearly paying the consequences, so for the last week I have purposely been eating my dinner between 8 and 9… then I take a heaping dose of honey 3 times a day plus 1 hour, or so, before bed and sleep like a log….I also have been eating spicy foods that normally would kill me… things like: spicy pasta sauces, curried vegetable sautés (with white onions!). I can even eat peanut butter, which was always instant death for me and wrecked my entire day.
"I started wondering if I was going nuts thinking that honey had cured my illness… so, last week I googled "the curative powers of honey". Your main man, Hippocrates, extolled the virtues of honey as a cure for digestive-related problems… and the anecdotal testimonies about honey from the ancient Greeks, Hebrews, Arabs go on and on.
"So there you have it… I have handed you the holy grail…you are the scientist in the family… you are the genius… you are the scientifically learned and gifted one… go explore this further.
"Just do me one favour – keep it in its simple, unadulterated form….don’t go finding the active ingredient in honey, isolate it, synthesize it, manufacture it in pill form that can only be purchased by prescription for $29.99 for a package of 12, that cannot be taken by people using beta-blockers, who have a history of high blood pressure, glaucoma, ulcers, rheumatoid arthritis, urinary tract or yeast infections, psoriasis, phlebitis, are pregnant or thinking of becoming pregnant…
"Don’t create side effects like dizziness, drowsiness, sexual dysfunction, bloating, diarrhea, blurred vision and heart palpitations….if you want to throw in an erection than lasts over 4 hours, okay, but no other side effects….if you promise me that, I will release all claims to any future royalties you receive, as well as any claim to earnings you get from the Nobel prize…..Deal? Deal."
"Coulda been a doc but no stomach for it…
Ken Brandes"
As you can now plainly see, insanity runs in my family. Yet the dividing line between insanity and brilliance is often razor-thin. Not only did my insanely brilliant brother stumble anew on the healing properties of honey, he humorously hit the nail squarely on the head when it comes to drug companies attempting to commercialize a natural substance!
Still, the question is begged: could pure, unadulterated honey, as a result of its antibacterial stomach-healing effects, out-perform the best, most expensive and side-effect-prone pills known to big pharma? Don’t hold your breath for industry to run a phase 3 trial testing that possibility! On the other hand if you have chronic heartburn that doesn’t respond well to those expensive prescription pills, try a dollop of natural liquid honey twice a day for a few weeks, see how you do, and let me know.
By the way, Ken reports that, after one false start, he was able to stop the honey altogether a few months back. He remains symptom-free, eats what he wants, and sleeps like a baby.
 
 
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June 19, 2016

6/19/2016

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The latest U.S. and Canadian task force study recommendations for screening mammograms are that only women at high risk for developing breast cancer, such as those with a family history, need be screened annually starting at age 40. For women at average to low risk, with no clinical concerns, screening mammograms every 2 to 3 years starting at age 50 may suffice. But other than those with a strong family history of breast cancer, who else should be considered at high risk? The answer in my CTV.ca/health blog from 2011 may surprise you!  
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​Are you at average risk for developing breast cancer? The answer may surprise you!

by Dr. Lorne Brandes  November 30, 2011 
 
Predictably, last week’s release of new breast cancer screening guidelines by the Canadian Task Force on Preventive Health Care (CTFPHC), like those issued by a similar U.S. task force in 2009, provoked a fierce public debate among advocates and opponents of mammography.
My major criticism of the report stemmed from the fact that all of its recommendations, from who should get screening mammograms (and at what interval), to women and doctors not performing routine breast examinations, were categorized by the CTFPHC panel as “weak”, meaning that, for each, “appreciable uncertainty” exists and that the level of evidence is not high. “Then why make them?” I asked .
Of all the recommendations, the greatest controversy surrounded the suggestion that, since breast cancer is much less common before age fifty, women aged 40 – 49 should not be routinely screened with mammograms.
The reason? Based on the large number needed to screen (2,100 per life saved), the 3.6% rate of unnecessary biopsies resulting from false-positive findings on mammograms (estimated at 327 per 1,000), and the anxiety provoked in such instances, the panel concluded that the harm of screening this younger group “probably” outweighed the benefit, despite the fact that, by its own account, mammograms every 1 to 2 years cut breast cancer deaths in this age group by 18%, saving an average of 474 lives per million women tested!
In publishing its new guidelines, the panel stressed that, regardless of age, its recommendations apply only to women considered at “average risk” for developing breast cancer, which it defined as: no previous breast cancer; no family history of breast cancer involving 1st-degree relatives; no known breast cancer gene mutations ( BRCA 1 or 2); no previous radiation to the chest wall.
But now, a paper just presented at the annual meeting of the Radiological Society of North America ( RSNA ) in Chicago, takes direct aim both at the CTFHPC screening guidelines for women 40-49 and at one bastion of the “average risk” equation: family history.
Radiologist, Dr. Stamatia Destounis, and her colleagues at the Elizabeth Wende Breast Care centre in Rochester, New York, studied over 1,000 women, aged 40 – 49, who had been diagnosed with breast cancer. Of those, 373 were diagnosed on a screening mammogram. And while 39% picked up on the mammogram had a family history of breast cancer, 61% did not . Moreover, the type and stage of cancer, determined at surgery, was identical in the two groups.
“In the 40 – 49 age group, we found a significant rate of breast cancer and similar rates of invasive disease [and lymph node involvement] in women with and without [a] family history. We believe this study demonstrates the importance of mammography screening for women in this age group, whether or not they have a family history, which is in opposition to the recommendations issued by the [U.S. and Canadian] task force[s]," Dr. Destounis said.
And, while I am in complete agreement with Dr. Destounis’ message, there are ten additional proven risk factors for breast cancer, not included in the CTFPHC or U.S. guidelines, that are highly important for every woman to know. They include:
  • Obesity (greater than 20% over ideal body weight)
  • Enlarged thyroid (including Hashimoto’s thyroiditis)
  • Diabetes
  • Never having been pregnant (nulliparity)
  • First pregnancy age 32+
  • Regular alcohol (all types) consumption starting in teenage years
  • Smoking, including chronic exposure to second-hand smoke
  • Prolonged use of oral contraceptives during reproductive years
  • Hormone replacement therapy (HRT) after menopause
  • Dense breast tissue on previous mammograms
Taking into account this information, are you really at “average risk” for developing breast cancer? If one or more items in this list apply to you, then your risk is significantly higher than average and I suggest you opt for regular screening mammograms starting at age 40!
And remember, this advice comes not from a panel of non-experts that issues broad statistical guidelines (which can never apply to a single individual), but from an oncologist who, for many decades, has specialized in the diagnosis and treatment of breast cancer and, quite frankly, has “seen it all”. 
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June 16, 2016

6/16/2016

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​At ASCO 2016, Oncologists reported the results of MA.17R, a randomised trial in which doubling the duration (from 5 to 10 years) of a daily oral dose of the aromatase inhibitor, letrozole,  in postmenopausal women with early stage breast cancer, resulted in a significant decrease in the risk of disease recurrence. However, the side effects of letrozole, including hot flashes, decreased libido, insomnia, joint pains and an increased risk of bone fractures can be hard on many women. This can make the decision to take letrozole for an additional 5 years very difficult for those at risk of recurrence who struggle with side effects. But did you know that women who have side effects with anastrazole, an aromatase inhibitor virtually identical to letrozole, actually have a lower risk of recurrence than women who don't have symptoms? Read more in this CTV.ca/health blog I posted in 2008.

Why Antiestrogen Side Effects May Predict Decreased Risk of Breast Cancer Recurrence
by Dr. Lorne Brandes  November 5, 2008 
 
A just-published article in The Lancet Oncology suggests that women with breast cancer who develop some common side effects (hot flashes, night sweats or joint pain) within three months of starting tamoxifen or the newer aromatase inhibitor drug, anastrazole (Arimidex), are less likely to have a recurrence of their disease when compared to women who do not.
These latest findings stem from an ongoing analysis of the clinical outcome in thousands of post-menopausal women with early breast cancer who, several years ago, participated in a large international phase three clinical study called ATAC.
Following initial surgery, radiation and/or chemotherapy, patients were randomized to receive five years of therapy with anastrazole alone, tamoxifen alone or both drugs in combination. The object of the trial was to determine which, if any, of the three hormonal regimens was superior to decrease recurrence.
After several years of follow up, it was observed that women who developed joint pains within three months of starting anastrazole had a 14 per cent recurrence rate, whereas women in whom the drug did not cause this symptom had a 23 per cent recurrence rate. Excluding joint pain (a side effect limited to anastrazole), women who developed hot flashes or night sweats within three months of starting either tamoxifen or anastrozole had a recurrence rate of 18 per cent compared to a 23 per cent recurrence rate in those who did not report these symptoms.
The authors concluded that the increased beneficial response associated with these somewhat unpleasant symptoms of antiestrogen therapy should be discussed with patients when deciding on whether to continue the treatment for the full five years.
Given the size of the ATAC study, the difference in recurrence rates, depending on the presence or absence of early side effects associated with tamoxifen or anastrazole, is a significant finding that should be taken seriously. Yet, how can we explain it?
The short answer is that the hot flashes, sweating and bone pain probably indicate an optimal concentration of the drug in the body.
There are at least three variables that determine concentration: how much of the drug is absorbed from the bowel; once absorbed, how efficiently the drug is metabolized in the liver (either broken down or converted to an active form); and whether other substances are present, such as fruit juices or certain medications, that may interfere with bowel absorption and/or liver metabolism of the drug.
The walls of cells lining the bowel are richly endowed with tiny pumps that transport drugs and other substances from the gut into the bloodstream. Recently it has been found that bowel absorption of many medications is significantly decreased when pills are washed down with various fruit juices that block the action of the pumps. Do women who drink juice to help them swallow tamoxifen or anastrazole have significantly lower bowel absorption than women who down their pills with water? A fundamental but most important question that requires an answer!
Perhaps the best studied variable is how drugs such as tamoxifen are broken down in the liver, where a large family of metabolizing enzymes, called P450, reside. To be clinically effective, tamoxifen first must be converted by certain P450 enzymes to two active forms: endoxifen and 4-hydroxy-tamoxifen.
However, significant genetically-determined variations in the P450 enzymes that metabolize tamoxifen have been observed. A 2005 study, published in the Journal of Clinical Oncology, linked the presence of a “normal” enzyme profile to both the occurrence of hot flashes and improved disease-free survival. Women who had one or more variant enzymes, associated with impaired conversion of tamoxifen to the active forms, tended not to have hot flashes and also had significantly worse clinical outcomes.
Finally, many drugs, including antidepressants such as fluoxetine (Prozac) and paroxetine (Paxil), can interfere with the metabolism of tamoxifen, resulting in lower concentrations of the antiestrogen. This likely occurs because they compete with tamoxifen for the same P450 liver enzymes, thereby decreasing the conversion of tamoxifen to its two active metabolites.
Some advice: if you have recently started therapy with tamoxifen or an aromatase inhibitor (including Arimidex, Femara and Aromasin) and are experiencing hot flashes and/or joint pain, try to stick with the medication. Those side effects may be telling you that you have an increased chance of benefit down the road.
However, if you are NOT experiencing side effects, first determine whether you are using a fruit juice to swallow your pill or check to see whether you may be taking one or more interfering medications. If neither is the case, speak to your oncologist about whether your metabolism of tamoxifen can be assessed (a tissue sample can be obtained using a buccal swab to obtain cells from the lining of the cheek). In the case of aromatase inhibitors, a check of residual estrogen levels in the blood can be carried out by most hospital labs. The answer may be of great importance to the outcome of your treatment.
 



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June 12, 2016

6/12/2016

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Advances in the treatment of multiple myeloma were highlighted at the recent ASCO meeting in Chicago. However, a gentle approach with 2 old drugs, cyclophosphamide and prednisone (CP), first reported by yours truly and Dr. Lyonel Israels in the 1980s, remains an option for older patients who can't tolerate aggressive chemotherapy. Moreover, CP has been shown to benefit myeloma patients who have failed bone marrow transplantation. Read more in my re-posted CTV,ca/health blog from 2009.
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Progress in treating multiple myeloma: New respect for a simple old treatment
December 16, 2009 07:21 by Dr. Lorne Brandes
 
Multiple myeloma (which means “many marrow tumours”) is a type of bone marrow cancer involving plasma cells that normally produce antibodies to protect us from infection. Because malignant plasma cells don’t function well, patients with myeloma may suffer frequent bouts of bacterial and viral illness.
 Moreover, as they divide, the cancerous plasma cells form chemical-secreting tumours that literally dissolve the bone around the marrow cavity, causing painful holes that can easily fracture. Almost always a fatal disease, multiple myeloma used to kill its victims within a few months to a year.
Interestingly, in 1949, Dr. Carman Weder, a Saskatoon physician, was the first to observe that the chemical, urethane, was effective in a patient with myeloma. Ultimately, the drug was abandoned after a clinical trial in 83 patients showed it to be both toxic and ineffective as compared to a placebo.
The modern era in myeloma treatment arrived with the synthesis, in the early 1950s, of a drug, called melphalan, at London’s Chester Beatty Research Institute (now called The Institute of Cancer Research).
Melphalan was first tested in humans by my mentor at the Royal Marsden Hospital, Dr. David Galton (see my post on Dr. Galton). He found that it predictably killed malignant plasma cells in the marrow, helped affected bones to heal, and appeared to prolong life. Melphalan was even more active when given along with a steroid drug, called prednisone. That combination, given the acronym “MP”, increased survival by two to three years, on average. As a result, MP became the gold standard against which any new treatment for myeloma was, and continues to be, compared.
Yet, although still in use all these years later, melphalan has a dark side. Because it is also very toxic to normal blood cells in the bone marrow, it increases the risk of infection and bleeding. This can be a major problem, especially in older people, in whom the disease is most frequent. As fate would have it, in the early 1980s, I stumbled across a much gentler drug treatment for myeloma.
Confronted with a gentleman whose bone marrow could not tolerate melphalan, I decided to substitute another active drug, called cyclophosphamide. However, because his blood counts were already perilously low and he needed transfusions, I settled on a much smaller single intravenous (IV) dose than usual. He was also given a prednisone pill to take every other day, rather than daily, to keep side effects to a minimum.
“Come back next week so we can check your blood,” I somewhat nervously advised after his first treatment.
When he reported back seven days later, everything was fine. His blood cells were holding their own. We gave him the same small IV dose of cyclophosphamide again and continued the prednisone pill every other day. With each weekly visit and treatment came an improvement in his condition. After three months, not only was he feeling much better and continuing to tolerate the drugs well, he no longer needed transfusions. All his blood counts had gone up while the plasma cells in the bone marrow were down by over half
"Can I tell you about a patient of mine?” I asked my illustrious boss, the late Dr. Lyonel Israels. An internationally-renowned hematologist, Lyonel had also spent time with Galton, in 1955, helping him develop another new cancer drug, CB1348, later called chlorambucil.
After listening to my story, Lyonel was eager to try the treatment on one of his own elderly patients who had stopped MP because of the side effects. A few months later, she too had improved significantly, and without appreciable toxicity.
Over the next four years, the two of us treated 20 patients with this simple regimen of weekly low-dose IV cyclophosphamide and alternate day oral prednisone; 10 had a major response while an additional five stabilized or improved.
"In myeloma, less is more," Lyonel quipped.
A country-wide trial followed, carried out by the National Cancer Institute of Canada. In confirming our findings, the researchers concluded that “the regimen of weekly cyclophosphamide and alternate-day prednisone may be as effective as more aggressive regimens in the treatment of patients with myeloma who have failed MP therapy.”
Yet, aside from a few Canadians, and David Galton and his colleagues in the U.K., nobody else seemed to be paying attention. The “zeitgeist” in the late 1980s, especially among American oncologists was that, where myeloma treatment was concerned, the more aggressive the better.
“Since it gets no respect, we should call it the ‘Rodney Dangerfield regimen’,” I lamented to Lyonel and my other Winnipeg colleagues.
And so it remained for the next 20 years, as stronger and stronger drugs were tried with much toxicity but little improvement in the outcome. Bone marrow transplants were pursued with modest success, but the mortality rate from the procedure remains considerable and most patients ultimately relapse.
Then, in 2005, came vindication… suddenly and without warning (at least to me). A study, published in the Mayo Clinic Proceedings, found that weekly cyclophosphamide and alternate-day prednisone (CP) “first introduced by Brandes and Israels” was “an effective, well-tolerated and convenient regimen” in patients with multiple myeloma who had failed a bone marrow transplant! Thirty-six of 66 patients responded to CP with a median survival of 28.6 months.
Subsequently, a 2008 study combining the CP regimen with bortezomib (Velcade) found “an unprecedented response rate [more than 50% complete remissions] and encouraging one-year survival [83%] in relapsed/refractory patients with [multiple myeloma].”
Now, as we head into 2010, myeloma patients have increasing reason to be optimistic, according to a statement just issued by the International Myeloma Foundation. Among the promising treatments cited by the foundation: a variation of the CP regimen, combined with bortezomib and another promising drug, called lenalidomide (Revlimid).
Respect has come late for our simple CP regimen. But come it has. How do I feel? To quote Jackie Gleason, “How sweet it is!”
 
 
 

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June 11, 2016

6/11/2016

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​As most readers know, mammography remains at the forefront of screening for early breast cancer, but not without controversy. As a result of in-depth meta-analyses assessing the number of lives saved per number of women screened, as well as the psychological trauma associated with biopsy following a possible "finding" (often a false-positive), the United States Preventive Services Task Force (USPSTF), along with its Canadian counterpart, has backed away from recommending yearly screening mammograms except in women considered at higher than average risk for developing breast cancer. But did you know that some suspect breast cancers on a mammogram may disappear with further followup? Read about the findings of a Norwegian study in this re-posted CTV.ca/health blog I wrote in 2008.

Why some early breast cancers may spontaneously disappear
November 30, 2008 13:33 by Dr. Lorne Brandes
 
​“I know I need to be screened, but every time I go for that test, I dread what my mammogram might show,” a patient recently confided to me.
She’s not alone. In the back of everyone’s minds is the thought that bad news could be forthcoming. Yet the assurance that, if diagnosed early, most breast cancers can be cured keeps women going back for the ordeal every year or two. After all, they (and we) are told that the more often breast cancer is caught and treated while the lump is too small to feel, the less likely the disease will become invasive, spread and, eventually, kill.
Now, the conventional wisdom of this notion has been shaken to some degree by a large new mammography study just published in the Archives of Internal Medicine. Norwegian doctors compared breast cancer incidence over a six-year period among 120,000 women between the ages of 50 and 64 who had three screening mammograms (one every two years) and 110,000 similarly aged women who had only a single mammogram at the end of the six-year period.
The doctors assumed that, regardless of when they were detected, the number of breast cancer tumours ultimately would be the same in each group, but the results came as a surprise. While, as expected, the cumulative number of breast cancers detected over six years in the screened group (1,909 cases per 100,000 population) was higher than in the control group (1,564 cases per 100,000 population), what was not expected was that, as compared to the screened group, the control group had 22 per cent fewer cancers detected on the single mammogram carried out at the end of the sixth year.
This outcome could not be explained by any obvious differences between the two groups. Therefore, the study’s authors raised the provocative possibility that “the natural course for some screen (mammogram)–detected breast cancers may be to spontaneously regress,” adding, for emphasis, “although many clinicians may be skeptical of the idea, the excess incidence (of cancer diagnoses) associated with repeat mammography demands that spontaneous regression be considered carefully.”
If this hypothesis is correct (and I, for one, believe it may be), what is the mechanism whereby up to one-in-five early breast cancers picked up on mammograms might shrink away without the need for treatment?
A major clue may be the age (50-64 years) of the population studied. What natural event occurs in most women between the ages of 50 and 55?
It’s the menopause, of course. Given that approximately two out of three breast cancer tumours are estrogen-driven, the sudden drop-off in ovarian estrogen at menopause may starve those estrogen-requiring cancers of the very hormone that drives their growth and development. As a result, they may either disappear over time or, in some cases, shrink and lie dormant without further growth.
There are other strong precedents in support of the “hormone hypothesis for spontaneous regression”: removing the ovaries, a common procedure for many decades in the treatment of metastatic breast cancer, often led to a dramatic, if temporary, shrinkage of large tumours. We can accomplish the same result today with specific drugs, called aromatase inhibitors, which block fat cells from producing estrogen.
Moreover, with the widespread discontinuance of hormone replacement therapy (HRT) for menopausal symptoms, the incidence of breast cancer world-wide has fallen rather dramatically over a very short period of time, consistent with a potent biological effect of hormone withdrawal to inhibit the development of breast cancer.
In an editorial accompanying the Norwegian study, cancer experts Drs. Robert M. Kaplan and Franz Porzsolt write: “If the spontaneous remission hypothesis is credible, it should cause a major reevaluation in the approach to breast cancer research and treatment. Certainly it is worthy of further evaluation.” I agree.
 


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June 9, 2016

6/9/2016

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​A new study suggests that type-2 diabetics who take metformin following a diagnosis of breast cancer lower their risk of dying of the disease by 50%. Here is a re-posting of my CTV.ca/health blog from 2009 reporting on the science behind the story.

Is the anti-diabetic pill metformin also effective against cancer?
June 17, 2009 07:49 by Dr. Lorne Brandes
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In my June 9 blog, I explained why off-patent drugs usually are not developed for new uses, such as cancer treatment. It generally boils down to money: because of the ready availability of cheaper generic versions, major pharmaceutical companies are reluctant to invest tens, or hundreds, of millions of dollars in the clinical cancer trials required to gain regulatory approval of a new use for their old drug.
Well, I have just learned that one old drug could prove to be an exception to that rule (As we say in medicine, “Never say ‘never’ and never say ‘always’”).
Its name is metformin, an oral medication widely used to treat adult (type 2) diabetes mellitus (DM2). Although its composition patent lapsed in 2002, and despite the fact that cheaper, FDA-approved, versions are now made by at least fifteen generic drug companies, metformin is still marketed under the trade name Glucophage by its original developer, Bristol-Myers, Squibb.
Given the increasing epidemic of DM2 in affluent countries of the western world, it seems that everyone still manages to reap a profit from this effective old warhorse!
Now comes exciting new evidence that what works in diabetes may also work in cancer. Here’s the story.
For some years, DM2 has been recognized as a risk factor for developing cancer. The association may be largely indirect, through obesity, which is prevalent in type 2 diabetics.
Too much body fat often results in what is called “insulin resistance”: far from producing too little insulin, the pancreas in obese subjects with DM2 produces too much of the hormone in response to the increased blood sugar. High levels of insulin and insulin-like growth factors (IGFs) are strongly implicated in the causation of cancer in laboratory rodents and in humans.
Metformin is especially effective in obese diabetics who overproduce insulin. By activating an important enzyme, called adenosine monophosphate kinase (AMPK), metformin prevents the liver from breaking down starch into sugar and stimulates uptake of sugar by the body’s muscles. As a result of this one-two punch, blood sugar and insulin levels fall.
Now for the cancer connection.
By activating the same AMPK enzyme in cancer cells, metformin inhibits malignant growth in the test-tube and in mice. The AMPK enzyme also interacts with other genes and proteins involved in aggressive malignant behaviour. Indeed, metformin is highly active in the test-tube against cells derived from “triple negative” breast cancer, a form of the disease with an especially poor prognosis.
Based on the accumulating laboratory data, researchers at Scotland’s University of Dundee compared the risk of cancer in 983 patients with DM2 who took metformin and 1,846 diabetic controls who did not in a study published in the British Medical Journal. They found that diabetic patients who took metformin had a significantly lower cancer rate. Those taking the highest doses of metformin for the longest period of time, had the lowest cancer rate (a 44% decrease as compared to diabetic controls who did not take metformin).
Now, with a just-released study published in the Journal of Clinical Oncology (JCO), the metformin train appears to be leaving the station.
Doctors at Houston’s M.D. Anderson Cancer Center assessed the effects of chemotherapy, given before surgery, on locally advanced breast cancer among 88 patients with DM2 who took metformin, 87 patients with DM2 who did not take metformin, and 2,374 non-diabetic patients. After the chemotherapy, all patients underwent mastectomy or lumpectomy; lymph nodes draining the breast were sampled in all cases.
Pathologists closely examined each surgical specimen under the microscope to determine the presence or absence of residual cancer cells. Cases in which there was no residual cancer following the chemotherapy were called “pathological Complete Responses (pCR)”.
The study found a significantly higher rate of pCR (24%) in patients with DM2 who took metformin at the time of chemotherapy than in patients with DM2 who did not take metformin at the time of chemotherapy (8% pCR). Non-diabetic patients also had a lower pCR rate (16%) than patients with DM2 who took metformin, but the difference did not reach significance.
In an accompanying JCO editorial entitled, “Metformin in breast cancer: Time for action,” the University of Toronto’s Dr. Pamela Goodwin and her colleagues announced plans for a large international phase 3 study to be led by the Clinical Trials Group of the National Cancer Institute of Canada. It will compare the effect of adding metformin or a placebo to chemotherapy following surgery for early breast cancer. The study will include both patients with DM2 and high insulin levels, and non-diabetic women.
Will metformin, the old, wildly successful anti-diabetic drug, morph into metformin, the new, wildly successful anti-cancer drug? Although nobody yet knows, one thing is certain: a positive outcome should generate even more hefty profits for both Bristol-Myers and its generic competitors!
 


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    Dr. Brandes is a retired oncologist, former CTV.ca blogger, and author of Survival: A Medical Memoir.

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