Promising Strategy in HER2 Positive Breast Cancer

Old_Quadrangle,_Manchester_1

University of Manchester, UK

Recently, in a Cancer Research UK study at the University of Manchester, remarkable results were reported in a clinical study of HER2+ breast cancer. Using the existing drugs trastuzumab (Herceptin) and lapatinib (Tyverb) together right after diagnosis, a quarter of women treated saw tumors shrink considerably, or even disappear, after just an average of 11 days.

Herceptin and Tyverb are not new to breast cancer treatment, but this study shows the possible effects of combining the drugs immediately after diagnosis in a pre-operative treatment. The study included 257 newly diagnosed women with operable, HER2+ tumors. Diagnoses were confirmed with biopsy.

While the trial was not originally designed to study these 2 drugs in this setting, the study was amended midway through as new data showed the synergistic effects of the drug combination. The women were randomized to a control group (no pre-operative treatment), Herceptin only, or the combination treatment for 11 days. Both groups proceeded to undergo surgical resection and receive standard treatment after surgery.

Among those women who received both drugs, 11% had a pathological complete response after surgery and 17% had minimal residual disease. In the control group, nobody showed either response.

References:

The Effects of Placebos in Cancer

Author Jo Marchant

Author Jo Marchant (photo credit: Garry Simpson/Crown)

Science writer Jo Marchant has written a fascinating book examining the role of the mind in healing. In her book “Cure: A Journey Into the Science of Mind Over Body“, Marchant separates the fact from fiction when it comes to mental strategies —and accidental benefits— when it comes to healing. This includes everything from meditation to prayer to the placebo effect.

The bottom line? Mental strategies usually help heal the body, and sometimes in profound ways rivaling medical interventions. Of course the underlying disease dictates the degree to which mental strategies show efficacy. Clearly, a placebo pill alone is not going to fix a compound fracture. But the effects of mental strategies are still surprising and intriguing, especially considering that most mental strategies have no adverse side-effects and no cost.

Studies have shown that pill size, color, and perceived cost all play significant roles in a treatment’s perceived effectiveness. A study of placebos in JAMA in 2008 showed that 85% of healthy volunteers found the “more expensive” pain reliever more effective, compared to 61% who used the “cheaper” pain reliever. All of the pills in this study were placebos, and contained no pain relief medicine. The fact that people found any pain relief at all is surprising. Researchers at the University of Cincinnati in 2015 found the same results in a much more serious setting: Parkinson’s disease. Other studies have shown that placebos sometimes even work when patients know they are taking placebos.

One of the most consistent benefits mentioned in Marchant’s book comes from compassion. Patients with friendly, supportive teams of family, friends and medical practitioners, do better as a group than those who do put together an effective team. Not surprisingly, patients seeing doctors with a good “bedside manner” generally do better than those who see cold, impersonal, doctors.

There is a growing body of science helping to explain why perception and other mental strategies have physiological effects. Many mental strategies such as visualization, meditation and prayer, have obvious benefits such as lower heart rate, blood pressure and stress levels. Many strategies have been examined in multiple, large clinical studies. Several peer reviewed studies have even tried to explore the science of prayer. Prayer has been shown to have “relaxation response” benefits similar to meditation. It should be noted, however, that intercessory prayer (praying for someone other than yourself) shows no statistical benefit if the patient is unaware of the prayer. Patients aware that someone is praying for them feel compassion, and thus receive a benefit.

The ramifications to cancer patients are also profound. If you view cancer prevention and therapy as probabilistic, where every potential benefit makes it more likely that you will succeed, a 5% gain is important. And there are many indications that mental strategies can result in benefits greater than 5%.

In 2009, Johns Hopkins published a large study of 1052 patients with high grade astrocytoma patients, which includes grade III and IV brain cancers. Their results showed that depression could affect overall survival by 20% or more, independent of treatment modality or degree of disability. This is an astounding figure, considering that many chemo drugs have lower efficacy rates, and hints at the importance of treating mental health during cancer treatment.

The ramifications of mental health strategies in cancer may be even more profound than currently realized, especially if some intriguing studies can be translated into therapies.

Scientists at MIT have discovered that rats who are raised in a low-stress environment produce more HDAC (histone deacetylase) inhibitors in their brains (or something which causes the equivalent result), while rats raised in stressful environments (with all other controls being equal) produce less. The difference may involve the same relaxation response as we see in meditation. Scientists were able to reverse an Alzheimer’s-like condition in the rats, simply by lowering their stress levels. The ramifications are potentially very important for cancer patients, because of the benefits of HDAC inhibitors both as radiosensitizing and therapeutic agents. Several HDAC inhibitors are already approved in cancer patients, including vorinostat (SAHA).

References:

Making Cancer Tumors Light Up for Surgeons

Tags

, , , , ,

What if surgeons could see a color-coded map on tissue, showing them where to work and what to avoid? That’s a goal oncologist Dr. Jim Olson has been trying to make reality for over a decade.

Tumor Paint in Mouse Brain

Tumor Paint in a mouse brain (the blue-green glow)

Using a unique molecule called chlorotoxin derived from the venom of the Deathstalker scorpion (L. quinquestriatus), Olson’s team figured out how to make cancer tumors glow. The idea is so exotic that it’s hard to believe, and for many years it was difficult for Olson to find funding for the research. When I first met Olson in 2009, he was busy with new research and another biotech startup, but he lit up, no pun intended, at the opportunity to talk about Tumor Paint. Today, Tumor Paint is in 2 clinical trials in humans, testing it in brain tumors and skin cancer.

Scorpion venoms have been used medicinally for perhaps thousands of years in China and India, but it wasn’t until 1993 that a team at Harvard identified and named chlorotoxin, which by itself is harmless to humans. Chlorotoxin is actually a peptide—a chain of amino acids which may have originally evolved to allow scorpions to paralyze the muscles of cockroaches. The following year, an MD-PhD student at the University of Alabama named Nicole Ullrich (now at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center) theorized and then proved that the newly defined chlorotoxin would bind to glioma brain cancer cells but not normal, healthy cells. This remarkable insight soon resulted in the first experimental cancer treatment, called radiolabeled TM-601, to use the properties of chlorotoxin.

Tumor Paint is a conjugated molecule consisting of the key components of chlorotoxin and Cy5.5, a cyanine dye with fluorescence. Because chlorotoxin has a high affinity for matrix-metalloproteinase (MMP-2), an enzyme which is activated and often upregulated in several virulent cancers, it homes in on cancer cells rather than healthy cells. Olson has found Tumor Paint accumulating in tissue as small as 200 cells, giving it an unusually high level of detail, especially when compared to common scanning methods such as MRI. When near-infrared light is shown on tissue infused with Tumor Paint, the cancerous tissue glows.

BLZ-100 (Tumor Paint)

BLZ-100 (Tumor Paint)

In July, 2013, a unique partnership began between the Fred Hutchinson Cancer Center in Seattle and the privately held biotech company Blaze Bioscience, to refine and commercialize Tumor Paint, now called BLZ-100. First Blaze won approval to test BLZ-100 in dogs, where it also found success. Today, BLZ-100 is in 2 human phase I clinical trials trying to determine the ideal dosage. A skin cancer trial is being conducted in Australia and a brain tumor trial in both Australia and the U.S. The U.S. trial, which has already treated half a dozen patients, is being conducted at Cedars-Sinai Medical Center under Dr. Chirag Patil.

References:

JAMA Study Identifies Specific BRCA Gene Mutations in Breast/Ovarian Cancers

Tags

, , , ,

The latest observational study of genomic data in women indicates that the location and type of mutation in BRCA genes play crucial roles in the odds of women getting breast or ovarian cancer. It has long been known that women who carry the BRCA1 or BRCA2 gene mutations are at increased risk for developing these cancers, however the new study, published today in the Journal of the American Medical Association (JAMA), goes into greater detail in identifying the specific mutations in these genes and the risks they create.

Mutations on BRCA1 Gene

Mutations on the BRCA1 Gene (Image courtesy NCI)

Preventive surgery with mastectomy (removal of breasts) or salpingo-oophorectomy (removal of ovaries and fallopian tubes) reduces a woman’s risk of breast and ovarian cancer by over 90%. Actress Angelina Jolie publicized her own story in 2013 of discovering a BRCA1 mutation, and her subsequent decision to have a double mastectomy to lower her future risk of cancer. But some women with BRCA1 or BRCA2 gene mutations will not develop cancer, thus more research is needed to help women make these critical decisions.

Today’s JAMA study, written by an international group of researchers, pooled data from 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. The data collected goes back almost 80 years, to 1937.

The study shows that among women with BRCA1 mutations, 46% are eventually diagnosed with breast cancer, 12% with ovarian cancer, and 5% with both. 37% of women with such mutations did not develop any cancer. Among women with the BRCA2 mutations, 52% were diagnosed with breast cancer, 6% with ovarian cancer, and 2% with both, while 40% did not develop cancer. This data backs up similar odds produced in a large study reported in JAMA by Israeli researchers in 2014.

Additionally, today’s study further identified 3 breast cancer and 1 ovarian cancer “cluster regions” for BRCA1, and another 3 cluster regions for each cancer in BRCA2. This information provides researchers a more detailed roadmap for determining specific cancer risks from BRCA1 and BRCA2 mutations. In the near future, screening for women may be able to better pinpoint the risk of breast and ovarian cancer to help women make the important decisions over prophylactic surgery.

Location of the BRCA1 gene on chromosome 17

Location of the BRCA1 gene on chromosome 17 (“BRCA1_en.png” by Kuebi (Armin Kübelbeck) / CC BY-SA 3.0)

BRCA1 and BRCA2, both identified in the early 1990s, are tumor suppressor genes, which when functioning normally, produce proteins which help control proper cell growth. Their proteins repair damaged DNA or destroy cells if the DNA can not be repaired. BRCA1 and BRCA2 are structurally different and located on different chromosomes, but are often discussed together because of their similar functions. Mutations in these genes allow a greater risk of developing breast, ovarian, and other types of cancer.

Prior to 2010, the publicly traded company Myriad Genetics in Salt Lake City, Utah, enforced their patents on the BRCA1 and BRCA2 genes, which many scientists argued stifled research and resulted in profoundly high prices for screening (e.g. $4,000 USD per test). Although researchers at the University of California, Berkeley, first discovered the location of BRCA1 on chromosome 17, Myriad was first able to sequence the gene. In June, 2013, in the landmark, unanimous decision of the US Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., the court held that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” At the time of this ruling, the US Patent and Trademark Office had already granted thousands of patents for human genes, accounting for almost 20% of the human body. Patent holders were previously given the right to prevent other researchers from studying a patented gene. It is entirely possible that research such as today’s JAMA paper would not be possible were it not for this ruling.

References:

Recent Advances Against Multidrug Resistance in Breast Cancer Cells

Tags

, , ,

In the Proceedings of the National Academy of Sciences for the week of March 2, scientists at MIT have reported on their novel method of overcoming drug resistance in cancer patients. Their idea sounds more like science fiction than reality.

As cancer tumors evolve over time, they often become resistant to chemotherapy treatments. Such a refractory tumor leads to a recurrence of cancer, which often grows faster, and is more deadly than originally.

The treatment developed by MIT scientists is based on a hydrogel implanted with gold nanoparticles and the chemo drug 5-fluorouracil (5-FU). The hydrogel is an aqueous solution of polyethylene glycol, or PEG, which has become a highly useful way of encapsulating bioactive molecules for easy transport into cells. 5-FU nanobeacons are added which serve as ON/OFF switches that are triggered by specific genes involved in drug resistance. To help make the 5-FU release more visible inside cells, the researchers labeled the drug with a near-infrared dye.

MIT-Nanoparticle-Treatment-Chart

The red bars show the dramatic decrease in cell viability after exposure to a nanoparticle treatment developed at MIT (2015, Artzi, in March 2, 2015 PNAS)

The MIT scientists implanted the nanoparticle treatment in a mouse model of human triple-negative breast cancer. This type of breast cancer is highly resistant to chemo treatments via the MRP1 (multidrug resistance protein 1) gene. In the mice, MRP1 expression triggered the nanoparticle 5-FU release, leading to a 90% tumor reduction. The researchers emphasized that this approach can be applied to other resistance genes and chemo drugs, calling the treatment a “universal nanotheranostic probe.”

The stability of the nanobeacons is excellent within a large pH range (4.5 to 8). Tumor environments are often more acidic than healthy cells.

Triple-negative breast cancer accounts for about 20% of breast cancers in the US, and 30% in African-American women. This particularly difficult-to-treat cancer is not driven by estrogen receptors, progesterone receptors, or HER2, giving it the “triple-negative” label. The lack of such receptors means triple-negative breast cancer does not respond to standard hormonal therapy (such as tamoxifen or aromatase inhibitors) or therapies that target HER2 receptors, such as Herceptin.

In December, 2014, another team at Johns Hopkins showed they could also reverse multidrug resistance by inhibiting the protein hypoxia-inducible factor, or HIF, which increases levels of MDR1 to pump chemo drugs out of the cancer cell. These researchers used the HIF inhibitor drug digoxin, which is already an FDA-approved drug for treating heart failure.

References:

Personalizing Cancer Treatments in Real-time

Tags

, ,

In 2013, the Dana-Farber Cancer Institute in Boston applied for a patent on something they called “Dynamic BH3 Profiling.” The patent description summarizes the invention as relating to “methods of predicting response to chemotherapy and in particular targeted therapies.”

This week, in the journal Cell, Dana-Farber researchers published their latest results of testing using this technique, showing that they can predict which chemo treatments will be most effective against a patient’s individual tumor within 16 hours of beginning the test. Such “real-time” testing will help achieve the goal of personalized treatment plans in cancer patients.

Dynamic BH3 Profiling Process

The Dynamic BH3 Profiling process. (Montero, Joan et al. Cell, Volume 160, Issue 5, 977 – 989, Feb. 26, 2015)

The Dana-Farber researchers, headed by Dr. Anthony Letai, has tested a wide variety of solid tumor and blood cancers using Dynamic BH3 Profiling, or DBP, including non-small cell lung cancers, breast cancers, colon cancers, leukemia, lymphoma, and multiple myeloma. To assess the accuracy of DBP, the researchers used the test to predict outcomes in patients taking standard treatments. DBP not only predicted cytotoxicity at a later time, but also predicted progression-free survival. Letai claims the DBP test is 80-90% accurate in predicting the best chemo treatment for an individual tumor sample, among a list of 20 popular common chemo drugs.

DBP measures how close a cancer cell is to apoptosis, or programmed cell death, a common destructive mechanism initiated by chemotherapy drugs. It detects an advance signal that a cancer cell is susceptible to the chemo drug, and this correlates with efficacy down the road. The test is performed on live tumor cells extracted from the patient, or viable cells from frozen tumor tissue. However the test can not work with cells preserved in the commonly used formalin.

Letai explains, “Regardless of the pathway inhibited, or what kind of cell the cancer started in, early drug-induced death signaling predicted later cytotoxicity.” The testing can also help predict the efficacy of combinations of therapeutic drugs. Genetic profiling is also a powerful way to predict drug sensitivity in tumors, but DBP can be done almost in real-time (overnight) and can detect properties in addition to genetic mutations which may point to certain treatments. In the future, DBP may be used in combination with other forms of testing to help create highly personalized treatment regimen.

DBP is still in the experimental phase, and Dana-Farber intends to continue testing the process with more series of patients in clinical trials. They hope to move the test into a clinical setting in the next couple years.

References:

Individualized Cancer Treatments Created in NCI MATCH Trial

Tags

, , ,

Besides the tremendous growth in unique and paradigm-shifting treatments, one of the biggest game-changing concepts for cancer patients is the notion that every tumor is different. While all cancer cells share certain biological similarities, individual tumors, even within the same type of cancer, exhibit a variety of differences which are becoming increasingly easier to detect using genetic and molecular profiling technologies. Even tumors within the same patient can have distinctly different characteristics, or characteristics within then same tumor which evolve over time. When it comes to cancer treatments, the long-held view that “one size fits all” is slowly being replaced with individualized treatments as part of personalized medicine.

Dr. Keith Flaherty

Dr. Keith Flaherty of Massachusetts General Hospital, principal investigator for the Match trial

At Massachusetts General Hospital, Dr. Keith Flaherty began testing individual patient tumors for genetic mutations and cell surface proteins he could then use to identify drugs which might be activated by those characteristics. In 2013, he teamed up with the pharmaceutical company AstraZeneca to use computer algorithms to identify combinations of treatments for individual tumors which might otherwise be unknown.

Most cancer patients today are treated with “one size fits all” chemotherapy and radiation treatments based on pivotal Phase III trials which established the current standard of care, even though it is readily established that a large portion of patients may not see any benefit from such treatments. Cancer patients at comprehensive cancer centers with specialized treatment clinics often receive sophisticated genetic and molecular profiling of tumor samples which help determine treatment regimens. In a Boston Globe interview in 2013, Edward Abrahams, president of the Personalized Medicine Coalition, an education and advocacy organization located in Washington, said, “At the end of the day, what we want to do is move away from one-size-fits-all medicine.”

Today Flaherty is the principal investigator for the National Cancer Institute’s Molecular Analysis for Therapy Choice Program (MATCH) phase II trial, which pairs next-generation tumor profiles with existing drugs which target specific genetic mutations. The MATCH trial is open to adult and pediatric patients with refractory tumors—cancers which have not responded to standard treatments and have relapsed.

The trial has already seen some profound successes. As the New York Times reported Feb. 25, many patients have seen their cancers completely disappear with treatments never designed with their type of cancer in mind. Dr. Richard Pazdur, who has been the FDA’s Director of the Office of Oncology Drug Products for the past decade, is watching these successes with great interest. He explains, “Conventional therapy might give a response rate of 10 or 20 percent.” But with individualized treatments, he’s seeing response rates of 50 to 60 percent. Response rates that high lead Pazdur to wonder whether it make sense to do a randomized or Phase III trial. “These are response rates we haven’t seen before in diseases” he says.

The NCI Match trial hopes to sequence the DNA of at least 3,000 tumors, pair each one with a likely drug, and then provide publish the results. The relatively inexpensive cost of DNA analysis is helping to make individualized cancer treatments practical. Other attempts to developed individualized chemo regimens involve chemosensitivity testing which subjects tumor samples to a wide variety of FDA-approved chemo drugs. But genetic and molecular profiling is much more efficient and flexible, theoretically allowing tumor profiles to be tested against the mechanism of any substance, including over-the-counter drugs or even food ingredients.’

References:

Curing “Terminal” Cancer

Tags

, , ,

Almost a decade ago, within days of my father being diagnosed with a glioblastoma brain tumor, I ran across a book by Professor Ben Williams PhD detailing his own battle against this same type of cancer. Ironically and fortuitously, Williams was a brain researcher working at UC San Diego, so he already knew quite a bit about brain biology. Williams’ tale of doggedly and resourcefully looking for a cure to his “terminal” cancer, knowing that the prognosis for newly diagnosed glioblastoma patients was just about 14 months, was exactly what I was looking for. My father died about 18 months after his diagnosis, but Williams survived his own glioblastoma, and a new documentary chronicles his story and the amazing research he pieced together.

Prof. Ben Williams

Prof. Ben Williams found a way to survive his own “terminal” cancer diagnosis.

Knowing the grim survival prognosis for glioblastoma, Prof. Williams immediately set about looking for additional ways he could treat his cancer, using his research skills to look up peer-reviewed, evidence-based approaches in PubMed, a government database of most medical studies. Almost immediately he began insisting that his oncologist add additional drugs to his treatment, inadvertently creating an early, ad-hoc cocktail cancer treatment in the process.

Most of the additional drugs Williams added to his regimen were “off-label”; they were FDA-approved for use in humans, but only for other diseases. To be approved for a particular disease, drugs usually need to go through pivotal Phase III trials which make use of a control group and hundreds of patients in order to establish a strong certainty of safety and efficacy. Unfortunately, Phase III trials are extremely expensive, as are the typical precursor Phase I and II trials. In 2014, an annual study from Tufts University stated that “developing a new prescription medicine that gains marketing approval, a process often lasting longer than a decade, is estimated to cost $2,558 million.” That’s over $2.5 billion, with a “B”.

Central to Professor Williams’ strategy was the notion of utilizing simultaneously a variety of non-toxic or low-toxic substances with non-overlapping mechanisms. In other words, Williams wanted to attack the cancer in as many different ways as possible, at the same time, without making himself too sick to be treated. Professor Williams and many oncologists view cancer as probabilistic—every evidence-based substance successfully added to a treatment regimen increases the probability that the cancer will successfully be treated. Many, many FDA-approved drugs have few or no adverse side-effects for most people.

Some of the off-label drugs Williams took included the acne drug Accutane and the antidepressant clomipramine. Accutane, or 13-cis-retinoic acid, is a powerful form of vitamin A which dries up your skin dramatically. Many retinoids like Accutane have anticancer properties. Clomipramine is an old tricyclic antidepressant whose main side-effect is sleepiness. Williams found both of these drugs cheaply in Mexico since they are both off patent. Williams also took, and continues to take, a wide variety of over the counter supplements, including fish oil, gamma-linolenic acid, lycopene, silibinin, curcumin, genistein, green tea, and melatonin.

The first part of Williams’ book Surviving Terminal Cancer centers on his diagnosis and treatment ordeal, emphasizing the need for patients to get up to speed on their treatment decisions so they can help advocate for the best treatment possible. The second half of his book, which he updates for free every year online, is an encyclopedia of drugs and food supplements with peer-reviewed evidence against cancer. The book should be required reading for cancer patients and their treatment teams, especially cancer patients with a Stage III or IV diagnosis.

A documentary premiered this month featuring Williams’ story, using the same title as his book, Surviving Terminal Cancer. Produced by Dominic Hill, the documentary is available to watch for free at SurvivingTerminalCancer.com. A trailer for the film can be viewed at:

References

Screening for Cancer Using Only Blood

Tags

,

One of the first medical traumas most newly-diagnosed solid tumor cancer patients struggle with is a biopsy. Many types of biopsies are painful and tricky to get, and sometimes the samples are less than ideal. Some tumors simply can not be biopsied due to their location. But recent advances in genomic sequencing are giving rise to a variety of non-invasive screening and pathology tests. A Silicon Valley company called Guardant now makes an FDA-approved blood test which provides virtually all of the information of a solid tumor biopsy, plus a lot more. The company, and some of it’s proprietary modeling technology, is profiled in yesterday’s USA Today.

GUARDANT HEALTH LOGO

Guardant tests blood samples for solid tumor DNA fragments

Guardant’s test, called Guardant360, became available in February, 2014, and has been used in some of the nation’s top cancer centers. This blood test measures cell-free DNA which is shed by solid tumors into the bloodstream. In doing so, the test is able to sequence DNA from any tumor locations in the patient’s body rather than just a single biopsy area. Guardant reports that, “Recent clinical studies with Guardant360 have shown excellent performance in the top five cancers (breast, lung, colorectal, skin and prostate).” The DNA fragments detected by Guardant’s test are often too small to be detected by other common DNA sequencing technologies. The company says its test enables “high-fidelity, single-molecule DNA sequencing and improves detection sensitivity well over 100-fold.”

Currently, Guardant360 is targeted for use by patients who have been diagnosed with a solid lesion which should be biopsied, or existing cancer patients needing to track their progress for treatment planning. The test results provided by Guardant360, which usually come back to the patient in 2 weeks, not only provides a specific solid tumor diagnosis (if evidence of a tumor is found), but associated treatment options and clinical trials based on the specific genomic alterations detected. Guardant360 does a 68-gene panel of sequencing, including common oncogenes such as EGFR, BRAF, and PTEN. Many tumors alter over time, and understanding how genomic alterations evolve in a specific tumor can help determine treatment options.

But Guardant is careful to say that it’s test does not predict responses to chemo treatments or provide prognosis. In theory, this type of information could, in fact, be determined with tests like Guardant360, but significant research to validate such claims would need to be completed. The use of Guardant360 purely for cancer screening in healthy adults is another area, which at least publicly, has not been discussed by Guardant.

Guardant claims they are currently the only company offering comprehensive genomic cancer testing from a blood sample, but the popularity and accessibility of genomic sequencing is bound to increase as the technology improves. Similar but much more narrow genomic blood tests currently exist for many types of cancer in various stages of development, including brain cancers for which biopsies are more challenging to acquire due to tumor locations.

References:

The Cancer Risk of Caramel Coloring in Soft Drinks

Tags

, ,

4-methylimidazole (4-MEI) is a carcinogen in the caramel coloring used in many foods, especially soft drinks. In 2011, California listed 4-MEI as a known carcinogen and determined safe levels in drinking water, after the US National Toxicology Program (NTP) conducted tests of 4-MEI in lab animals. The NTP found “clear evidence” that 4-MEI increased incidence of cancer in rats, while noting that no human studies have been done to date.

Researchers at Johns Hopkins this week released a paper in the prestigious journal PLOS ONE extrapolating known quantities of 4-MEI in soft drinks into cancer incidence predictions. The analysis shows that with current soft drink consumption rates in the US, up to 5,000 cases of new cancers could be caused by the 4-MEI in one brand of soft drink alone in the next 70 years.

Diet Coke Can

Diet Coke had the lowest measured levels of 4-MEI amongst soft drinks tested

There are currently no regulations in US on how much 4-MEI can be included in foods, however in California, if a food contains more than 29 micrograms (mcg) of 4-MEI, the product must be labeled as containing a carcinogen. At this level, the cancer risk is one per 100,000 people exposed. A 2013 study found that 4-MEI levels in common soft drinks ranged from 3.4 to 352.4 mcgs per 12-ounce soda. Malta Goya had the highest amounts, while Diet Coke had the lowest. For Malta Goya drinkers, they are consuming over 10 times the amount of 4-MEI considered an acceptable cancer risk. The Johns Hopkins researchers noted that “4-MEI concentrations varied considerably by soda and state/area of purchase, but were generally consistent across lots of the same beverage purchased in the same state/area.”

Since caramel coloring adds nothing to flavor and is often not even seen by the consumer if drinking from an aluminum can, many manufacturers are looking for safer alternatives in light of the public and California concerns. 4-MEI is not even an added ingredient of caramel coloring, but a byproduct formed during the manufacturing process. The FDA still lists caramel color as “Generally Recognized As Safe” despite the research data. In 2012, the Center for Science in the Public Interest petitioned the FDA to prohibit Class III and Class IV caramel colors, the most common types.

In 2007, a controversial study by the University of Southampton in the UK found that 6 artificial colors were linked to hyperactivity in children. As a result, European food manufacturers have made more progress than their US counterparts in replacing artificial colors with natural colors. Stefan Hake, CEO of GNT USA in New York noted that “all the (Southampton) colors listed can be replaced with fruit- and vegetable-based colors.” Several natural food colors such as tumeric and carotenoids ironically have anticancer properties.

References: