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Published on Leave a comment on Vitamin D Level Linked to Cancer Risk

 A number of recent studies looked at vitamin D and various diseases. All showed benefits of higher vitamin D levels in the blood: lower rates of cancer incidence, improved heart function in those with heart failure, lower rates of leukemia incidence, lower rates of breast cancer, and less aggressive breast and prostate cancer. However, one study found no benefits to vitamin D supplementation during pregnancy and the child's asthma risk. Older studies found low levels of vitamin D linked to higher risk of premenopausal breast cancer, and also to thicker melanomas at diagnosis (the thinner the melanoma, the better the prognosis).

Everyone agrees that sunshine is an excellent source of vitamin D, but there is still disagreement over what are the best daily vitamin D supplement dosages, or even what are optimal levels of vitamin D in the blood (measured as serum 25-hydroxyvitamin D or 25(OH)D). In 2010, the Institute of Medicine (IOM) concluded that levels lower than 12 ng/ml represented a vitamin D deficiency and recommended a target of 20 ng/ml, which could be met in most healthy adults (ages 19 to 70) with 600 International Units of vitamin D each day. Since then most researchers have argued for higher blood serum levels: most agreeing that over 30 ng/ml is best, while some advocating 50 ng/ml or more. But even what's too high (and could cause problems) is debated. Many vitamin D supporters now advocate taking 800 to 1,000 IUs of vitamin D daily (some say up to 4000 IUs daily is OK). Remember to look for vitamin D3 supplements, not D2.

This study found that higher levels of vitamin D (measured as serum 25(OH)D) are better, with 25(OH)D concentrations of at least 40 ng/ml best to reduce cancer risk (all types of cancer). From Medical Xpress: Higher levels of vitamin D correspond to lower cancer risk, researchers say

Researchers at University of California, San Diego School of Medicine report that higher levels of vitamin D - specifically serum 25-hydroxyvitamin D - are associated with a correspondingly reduced risk of cancer. The findings are published in the April 6, online issue of PLOS ONE.

Garland and his late brother, Frank, made the first connection between vitamin D deficiency and some cancers in 1980 when they noted populations at higher latitudes (with less available sunlight) were more likely to be deficient in vitamin D, which is produced by the body through exposure to sunshine, and experience higher rates of colon cancer. Subsequent studies by the Garlands and others found vitamin D links to other cancers, such as breast, lung and bladder.

The new PLOS ONE study sought to determine what blood level of vitamin D was required to effectively reduce cancer risk....The only accurate measure of vitamin D levels in a person is a blood test....Cancer incidence declined with increased 25(OH)D. Women with 25(OH)D concentrations of 40 ng/ml or greater had a 67 percent lower risk of cancer than women with levels of 20 ng/ml or less.

Garland does not identify a singular, optimum daily intake of vitamin D or the manner of intake, which may be sunlight exposure, diet and/or supplementation. He said the current study simply clarifies that reduced cancer risk becomes measurable at 40 ng/ml, with additional benefit at higher levels. "These findings support an inverse association between 25(OH)D and risk of cancer," he said, "and highlight the importance for cancer prevention of achieving a vitamin D blood serum concentration above 20 ng/ml, the concentration recommended by the IOM for bone health."

From Science Daily: Vitamin D improves heart function, study finds

A daily dose of vitamin D3 improves heart function in people with chronic heart failure, a five-year research project has found. The study involved more than 160 patients who were already being treated for their heart failure using proven treatments including beta-blockers, ACE-inhibitors and pacemakers.

Participants were asked to take vitamin D3 or a dummy (placebo) tablet for one year. Those patients who took vitamin D3 experienced an improvement in heart function which was not seen in those who took a placebo....In the 80 patients who took Vitamin D3, the heart's pumping function improved from 26% to 34%. In the others, who took placebo, there was no change in cardiac function.

Disappointing results. From Medscape: Vitamin D Disappoints: Prenatal Supplementation and Childhood Asthma

Two recent clinical trials examined maternal supplementation with vitamin D and postpregnancy offspring outcomes for asthma and wheezing....However, with respect to preventing asthma in offspring, there is no clear evidence for vitamin D supplementation in pregnant women.

From PLOS ONE: Vitamin D Deficiency at Melanoma Diagnosis Is Associated with Higher Breslow Thickness

Vitamin D deficiency at the time of melanoma diagnosis is associated with thicker tumours that are likely to have a poorer prognosis. Ensuring vitamin D levels of 50 nmol/L or higher in this population could potentially result in 18% of melanomas having Breslow thickness of <0.75 mm rather than ≥0.75 mm.

Reported in 2013. From Medical Express: Low vitamin D levels linked to high risk of premenopausal breast cancer

A prospective study led by researchers from the University of California, San Diego School of Medicine has found that low serum vitamin D levels in the months preceding diagnosis may predict a high risk of premenopausal breast cancer. The study of blood levels of 1,200 healthy women found that women whose serum vitamin D level was low during the three-month period just before diagnosis had approximately three times the risk of breast cancer as women in the highest vitamin D group. 

A 2011 meta-analysis by Garland and colleagues estimated that a serum level of 50 ng/ml is associated with 50 percent lower risk of breast cancer. While there are some variations in absorption, those who consume 4000 IU per day of vitamin D from food or a supplement normally would reach a serum level of 50 ng/ml.

Published on Leave a comment on Low Vitamin D Levels Linked to Aggressive Cancer

Two recent studies link low vitamin D levels with more aggressive cancers: aggressive prostate cancer in men and more aggressive breast cancers (in mice and women). Researchers generally advise people to take 1000 to 2000 international units per day of vitamin D3 to maintain normal blood levels of of more than 30 nanograms/milliliter. The best source of vitamin D is sunlight, which is why vitamin D is frequently called the sunshine vitamin.

From Science Daily:  Low vitamin D predicts aggressive prostate cancer

A new study provides a major link between low levels of vitamin D and aggressive prostate cancer. Northwestern Medicine research showed deficient vitamin D blood levels in men can predict aggressive prostate cancer identified at the time of surgery.

"Vitamin D deficiency may predict aggressive prostate cancer as a biomarker," said lead investigator Dr. Adam Murphy, an assistant professor of urology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine urologist. "Men with dark skin, low vitamin D intake or low sun exposure should be tested for vitamin D deficiency when they are diagnosed with an elevated PSA or prostate cancer. Then a deficiency should be corrected with supplements."

Aggressive prostate cancer is defined by whether the cancer has migrated outside of the prostate and by a high Gleason score. A low Gleason score means the cancer tissue is similar to normal prostate tissue and less likely to spread; a high one means the cancer tissue is very different from normal and more likely to spread. The study was part of a larger ongoing study of 1,760 men in the Chicago area examining vitamin D and prostate cancer. The current study included 190 men, average age of 64, who underwent a radical prostatectomy to remove their prostate from 2009 to 2014.

Of that group, 87 men had aggressive prostate cancer. Those with aggressive cancer had a median level of 22.7 nanograms per milliliter of vitamin D, significantly below the normal level of more than 30 nanograms/milliliter. The average D level in Chicago during the winter is about 25 nanograms/milliliter, Murphy noted....The Institute of Medicine recommends 600 international units of D per day, but Murphy recommends Chicago residents get 1,000 to 2,000 international units per day.

From Medical Xpress:  Vitamin D deficiency contributes to spread of breast cancer in mice, study finds

Breast tumors in laboratory mice deficient in vitamin D grow faster and are more likely to metastasize than tumors in mice with adequate levels of vitamin D, according to a preliminary study by researchers at the Stanford University School of Medicine.The research highlights a direct link between circulating vitamin D levels and the expression of a gene called ID1, known to be associated with tumor growth and breast cancer metastasis.

The finding builds upon several previous studies suggesting that low levels of vitamin D not only increase a person's risk of developing breast cancer, but are also correlated with more-aggressive tumors and worse prognoses. Although the research was conducted primarily in mice and on mouse cells, the researchers found in a study of 34 breast cancer patients that levels of circulating vitamin D were inversely correlated with the expression levels of ID1 protein in their tumors, and they confirmed that a vitamin D metabolite directly controls the expression of the ID1 gene in a human breast cancer cell line.

Once ingested or made by the body, vitamin D is converted through a series of steps into its active form, calcitriol. Calcitriol binds to a protein in cells called the vitamin D receptor, which then enters the cell's nucleus to control the expression of a variety of genes, including those involved in calcium absorption and bone health.

In the new study, Williams and Aggarwal investigated whether vitamin D levels affected the metastatic ability of mouse breast cancer cells implanted into the mammary fat pad of laboratory mice. One group of 10 mice was first fed a diet lacking in the vitamin for 10 weeks; the other 10 received a normal dose in their food. Mice fed a diet deficient in vitamin D developed palpable tumors an average of seven days sooner than their peers, and after six weeks of growth those tumors were significantly larger in size than those in animals with adequate vitamin D levels.

Published on Leave a comment on More On Rethinking Cancer Screening

The following is an excellent commentary by Dr. John Mandrola regarding an important British Medical Journal article that I posted about earlier (see Rethinking Cancer Screening). He has a highly regarded web-site and also frequently posts on Medscape. His view is that cancer screening "may be one of Medicine’s largest reversals. A reversal happens when something (testing or treatment) doctors did, and patients accepted, turned out to be non-beneficial." (www.drjohnm.org)

I can't overstate how big a reversal this is in medicine - it's huge, a paradigm change in the making. The reason for this is that studies show that overall death rates are basically the same in screened vs non-screened for mammography, colon, prostate, and lung cancer screening. This means our view of how cancer grows and spreads may have to be reexamined and changed. One possibility suggested by Dr. H. Gilbert Welch is that aggressive cancer is already "a systemic disease by the time it's detectable" (Oct. 28, 2015 post).  From Medscape:

In Cancer Screening, Why Not Tell the Truth?

The problem: cancer screening has not worked. Recent reviews of the evidence show that current-day screening techniques do not save lives. Worse, in many cases, these good-intentioned searches bring harm to previously healthy people.

I realize this sounds shocking. It did to me, too. Millions of women and men have had their breasts squished, veins poked, lungs irradiated, and bowels invaded in the name of "health" maintenance. I've been scolded for forgoing PSA tests and colonoscopy — "you should know better, John."....Anecdotes, however compelling, are not evidence. When you pull up a chair, open your computer, take a breath, suspend past beliefs, and look for the evidence that screening saves lives, it simply isn't there.

One reason that this many people (doctors and patients alike) have been misled about screening has been our collective attachment to the belief that if screening lowers disease-specific death rates, that would translate to lower overall mortality. That is: breast, lung, and colon cancer are bad diseases, so it makes sense that lowering death from those three types of cancer would extend life. It is not so.

In a comprehensive review of the literature[1] published in the BMJ, Drs Vinay Prasad (Oregon Health Sciences University, Portland) and David Newman (School of Medicine at Mount Sinai, New York), along with journalist Jeanne Lenzer, find that disease-specific mortality is a lousy surrogate for overall mortality. They report that when a screening technique does lower disease-specific death rates, which is both uncommon and of modest degree, there are no differences in overall mortality.

The authors cite three reasons why cancer screening might not reduce overall mortality:

  • Screening trials were underpowered to detect differences. I'm no statistician, but doesn't the fact that a trial requires millions of subjects to show a difference, mean there is little, if any, difference?
  • "Downstream effects of screening may negate any disease-specific gains." My translation: harm. Dr Peter Gøtzsche (Nordic Cochrane Center, Copenhagen) wrote in a commentary[2] that "screening always causes harm. Sometimes it also leads to benefits, and sometimes these benefits outweigh the harms." To understand harm resulting from screening, one need only to consider that a prostate biopsy entails sticking a needle through the rectum, or that some drugs used to treat breast cancer damage the heart.
  • Screening might not reduce overall mortality because of "off-target deaths." An illustration of this point is provided by a cohort study[3]that found a possible increased risk of suicide and cardiovascular death in men in the year after being diagnosed with prostate cancer. People die — of all sorts of causes, not just cancer.

Let's also be clear that this one paper is not an outlier. A group of Stanford researchers performed a systematic review and meta-analyses[4] of randomized trials of screening tests for 19 diseases (39 tests) where mortality is a common outcome. They found reductions in disease-specific mortality were uncommon and reductions in overall mortality were rare or nonexistent.

Drs Archie Bleyer and H Gilbert Welch (St Charles Health System, Central Oregon, Portland) reviewed Surveillance, Epidemiology, and End Results (SEER) data from 1976 through 2008 and concluded that "screening mammography has only marginally reduced the rate at which women present with advanced cancer and that overdiagnosis may account for nearly a third of all new breast cancer cases."[5] Likewise, a Cochrane Database Systematic review[6] of eight trials and 600,000 women did not find an effect of screening on either breast cancer mortality or all-cause mortality. This evidence caused the Swiss medical board to abolish screening mammography.[7]

These are the data. It's now clear to me that mass cancer screening does not save lives. But I'm still trying to understand how this practice became entrenched as public-health gospel. It has to be more than fear. Dr Gerd Gigerenzer (Max Planck Institute, Berlin, Germany)...He pointed to language and the ability of words to persuade. Instead of saying "early detection," advocates might use the term "prevention." This, Dr Gigerenzer says, wrongly suggests screening reduces the odds of getting cancer. Doesn't looking for cancer increase the odds of getting the diagnosis of cancer?

Gigerenzer noted two other ways language is used to emphasize screening benefits over harms: -The reporting of benefits in relative, not absolute terms. - The equating of increases in 5-year survival rates with decreases in mortality. I would add to this list of word misuse, the practice of referring to women sent to mammography screening as patients. They are not patients; they are well people. Dr Gigerenzer agreed with the commonsense notion that overall mortality should be reported along with cancer-specific mortality. His editorial included a fact box on breast cancer early detection using mammography provided by the Harding Center for Risk Literacy. I challenge you to tell me why such text boxes should not be shown to people before they undergo screening,

The first action healthcare experts should take is to spread the word that there is nothing about the mass screening of healthy people for cancer that equates to health maintenance. Embrace clear language. Saying or implying that screening saves lives when there are no data to support it and lots to refute it undermines trust in the medical profession.

The second action healthcare experts should take is to stop wasting money on screening. If the evidence shows no difference in overall mortality, why pay for it? I'm not naive to the fact that use of clear language will decrease the number of billable procedures. I am not saying this will be easy. One first move that would be less painful would be to get rid of quality measures or incentives that promote screening.

I want to be clear; I'm not saying all cancer screening is worthless. People at higher baseline risk for cancer, such as those with a family history of cancer or environmental exposures, might derive more benefit than harm from screening. Prasad, Lenzer, and Newman say this group of patients would be a good place to spend future research dollars. That sounds reasonable. I also acknowledge that some people, even when presented with the evidence, will want to proceed with screening. We can argue about who should pay for non–evidence-based medical procedures.

Published on Leave a comment on Rethinking Cancer Screening

A provocative and thought-provoking article in which the title says it all: Cancer screening has not been shown to 'save lives'. The following is from the Medscape analysis/reporting of the original British Medical Journal article and accompanying editorial ( BMJ. January 2016, Article, Editorial), and both the original and Medscape analysis are well worth reading. From Medscape:

Cancer Screening Has Not Been Shown to 'Save Lives'

Debates about cancer screening programs tend to focus on when to start, who to screen, and the frequency of screening. But some investigators are asking a far more provocative question: Do screening programs actually save lives?

We do not know the answer to that question, and would need to conduct massive clinical trials to find out, said Vinay K. Prasad, MD, MPH, assistant professor of medicine at the Oregon Health Sciences University in Portland."Proponents of cancer screening say that screening tests have been shown to save lives. What we're trying to show is that, strictly speaking, that's sort of an overstatement," he told Medscape Medical News.

In an analysis published online January 6 in the BMJ, Dr Prasad and his colleagues argue that although cancer screening might reduce cancer-specific mortality, it has not conclusively been shown to have an effect on overall mortality. The researchers go on to suggest that the harms of screening might actually contribute to overall mortality rates. These potential harms include false-positive results that lead to unnecessary biopsies or therapeutic interventions and overdiagnosis, in which treatment is delivered for a condition that is unlikely to affect patients during their natural lifespans.

"There are two chief reasons why cancer screening might reduce disease-specific mortality without significantly reducing overall mortality," the researchers write. "Firstly, studies may be underpowered to detect a small overall mortality benefit. Secondly, disease-specific mortality reductions may be offset by deaths due to the downstream effects of screening." "The bar to say that screening saves lives should be overall mortality, and we haven't met that bar," Dr Prasad told Medscape Medical News.

The rationale for cancer screening is based on the assumptions that screening will reduce deaths from cancer and that lowering cancer-specific deaths will decrease overall mortality. These assumptions remain unsupported by facts, Dr Prasad's team contends.

They illustrate this point with data from the National Lung Cancer Screening Trial (NLST). Although there was a 20% relative reduction in lung cancer deaths with low-dose CT screening, compared with chest x-ray, and a 6.7% relative reduction in overall mortality, the absolute reduction in risk for overall mortality was just 0.46%....The team also notes that "the benefit in lung cancer mortality of CT screening (estimated to avert over 12,000 lung cancer deaths in the United States annually) must be set against the 27,034 major complications (such as lung collapse, heart attack, stroke, and death) that follow a positive screening test."

The decision to undergo screening should be part of an informed discussion between the patient and clinician that takes into account personal preferences and the risks and benefits of screening. Dr Prasad explained. "Declining screening may be a reasonable and prudent choice for many people," the researchers write. "Doctors should be comfortable with whatever choice people make when they hear about all the potential benefits and the known harms," Dr Prasad added.

However, in an accompanying editorial, Gerd Gigerenzer, PhD, from the Max Planck Institute for Human Development in Berlin, argues that "rather than pouring resources into 'megatrials' with a small chance of detecting a minimal overall mortality reduction, at the additional cost of harming large numbers of patients, we should invest in transparent information in the first place." He explains that information about screening should be presented in a "fact box" that lays out the benefits and risks of mammography with numbers for how many women would be affected."It is time to change communication about cancer screening from dodgy persuasion into something straightforward," he concludes.

Richard L. Schilsky, MD, chief medical officer for the American Society of Clinical Oncology (ASCO), said that although, in general, ASCO supports cancer screening, "it's a very imperfect process....The often high variability in the natural history of many cancers has been the source of particular confusion and uncertainty surrounding screening, he noted. For example, there is little value in screening for aggressive cancers for which interventions are unlikely to make a difference in outcomes, no matter how early the disease can be detected. Conversely, "if the cancer is never going to kill you, no matter what the doctors do, then screening won't help either," he said. Additionally, there are some cancers for which treatments are sufficiently effective that they can be successfully managed whether they are diagnosed at an early or later stage. "When you consider all these factors, the number of individuals who will actually benefit from detecting a screen-detected cancer is very small," Dr Schilsky said.

Published on Leave a comment on Sugar in Western Diet and Breast Cancer

This study was done in mice, but...it may apply to humans. The researchers found that sugar intake in mice comparable with levels in Western diets (in humans) led to increased breast tumor growth and metastasis.They specifically found that table sugar and high fructose corn syrup "was responsible for facilitating lung metastasis and 12-HETE production in breast tumors" in mice. So, at the very least, think about eliminating high fructose corn syrup from the diet - read labels and definitely eliminate soda (a huge source of added high fructose corn syrup).From Science Daily:

Sugars in Western diets increase risk for breast cancer tumors and metastasis

The high amounts of dietary sugar in the typical Western diet may increase the risk of breast cancer and metastasis to the lungs, according to a study at The University of Texas MD Anderson Cancer Center.The findings, published in the Jan. 1, 2016 online issue of Cancer Research, demonstrated dietary sugar's effect on an enzymatic signaling pathway known as 12-LOX (12-lipoxygenase).

"We found that sucrose intake in mice comparable to levels of Western diets led to increased tumor growth and metastasis, when compared to a non-sugar starch diet," said Peiying Yang, Ph.D., assistant professor of Palliative, Rehabilitation, and Integrative Medicine. "This was due, in part, to increased expression of 12-LOX and a related fatty acid called 12-HETE." Previous epidemiological studies have shown that dietary sugar intake has an impact on breast cancer development, with inflammation thought to play a role.

"The current study investigated the impact of dietary sugar on mammary gland tumor development in multiple mouse models, along with mechanisms that may be involved," said co-author Lorenzo Cohen, Ph.D., professor of Palliative, Rehabilitation, and Integrative Medicine. "We determined that it was specifically fructose, in table sugar and high-fructose corn syrup, ubiquitous within our food system, which was responsible for facilitating lung metastasis and 12-HETE production in breast tumors." Cohen added that the data suggested that dietary sugar induces 12-LOX signaling to increase risks for breast cancer development and metastasis.

Identifying risk factors for breast cancer is a public health priority, say the authors. The researchers state that moderate sugar consumption is critical, given that the per capita consumption of sugar in the U.S. has surged to over 100 lbs. per year and an increase in consumption of sugar-sweetened beverages has been identified as a significant contributor to an epidemic of obesity, heart disease and cancer worldwide.

The MD Anderson team conducted four different studies in which mice were randomized to different diet groups and fed one of four diets. At six months of age, 30 percent of mice on a starch-control diet had measurable tumors, whereas 50 to 58 percent of the mice on sucrose-enriched diets had developed mammary tumors. The study also showed that numbers of lung metastases were significantly higher in mice on a sucrose- or a fructose-enriched diet, versus mice on a starch-control diet.

Published on Leave a comment on Periodontal Disease Associated With Increased Breast Cancer Risk

Image result for teeth, wikipedia Research found that postmenopausal women with periodontal disease (gum disease) were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. And it's a bigger risk among those who currently smoke or quit smoking within the last 20 years. The interesting part is the fact that periodontal disease is a bacterial disease and that it results in inflammation. An earlier post discussed research that found that the human breast microbiome (microbial community) and specifically the bacteria, is different in healthy breasts (in the breast tissue) as compared to cancerous breasts. From Science Daily:

Periodontal disease associated with increased breast cancer risk in postmenopausal women

Postmenopausal women with periodontal disease were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. A history of smoking significantly affected the women's risk, researchers report. Periodontal disease is a common condition that has been associated with heart disease, stroke, and diabetes. Previous research has found links between periodontal disease and oral, esophageal, head and neck, pancreatic, and lung cancers, so the researchers wanted to see if there was any relationship with breast cancer.

Jo L. Freudenheim, PhD, and colleagues monitored 73,737 postmenopausal women enrolled in the Women's Health Initiative Observational Study, none of whom had previous breast cancer. Periodontal disease was reported in 26.1 percent of the women. Because prior studies have shown that the effects of periodontal disease vary depending on whether a person smokes, researchers examined the associations stratified by smoking status.

After a mean follow-up time of 6.7 years, 2,124 women were diagnosed with breast cancer. The researchers found that among all women, the risk of breast cancer was 14 percent higher in women who had periodontal disease.

Among women who had quit smoking within the past 20 years, those with periodontal disease had a 36 percent higher risk of breast cancer. Women who were smoking at the time of this study had a 32 percent higher risk if they had periodontal disease, but the association was not statistically significant. Those who had never smoked and had quit more than 20 years ago had a 6 percent and 8 percent increased risk, respectively, if they had periodontal disease.

"We know that the bacteria in the mouths of current and former smokers who quit recently are different from those in the mouths of non-smokers," Freudenheim explained. One possible explanation for the link between periodontal disease and breast cancer is that those bacteria enter the body's circulation and ultimately affect breast tissue. However, further studies are needed to establish a causal link, Freudenheim said.

Published on Leave a comment on Time to Ditch Personal Care Products Containing Parabens?

Even though many, many personal care products contain parabens, the evidence is accumulating that parabens have negative health effects. And now research suggesting that perhaps they may be a factor in developing breast cancer. This latest study was done "in vitro" - meaning looking at the effects of chemicals on human breast cells (in culture dishes), but the results absolutely should make someone think twice about all the parabens in products, and how they accumulate in us. Research has already found parabens in the human breast, but many thought that the levels were too low to promote cancer.

Parabens are common ingredients in cosmetics, shampoos, body lotions and sunscreens, where they are used to prevent microbial growth and prolong shelf life.  Common names of parabens are: methylparaben, ethylparaben, propylparaben, and butylparaben. Detectable levels of multiple parabens are present in human urine and breast tissue. Bottom line: Parabens are endocrine disrupting chemicals that mimic estrogens and may have effects at very low doses to stimulate breast cancer cell growth. So read labels of personal care products and avoid those with parabens. From Futurity:

New Tests Suggest Parabens Carry Cancer Risk

A group of chemicals called parabens—common ingredients in personal care products—may interact with growth factors in the body to increase the risk of breast cancer, according to new research. Parabens are preservatives widely used in everything from shampoos and cosmetics to body lotions and sunscreens. The chemicals have generated increasing health concerns, however, because they mimic estrogens, which have been linked to an increased risk of breast cancer and reproductive problems.

“Although parabens are known to mimic the growth effects of estrogens on breast cancer cells, some consider their effect too weak to cause harm,” says lead investigator Dale Leitman, a gynecologist and molecular biologist at the University of California, Berkeley, and an adjunct associate professor of nutritional sciences and toxicology. “But this might not be true when parabens are combined with other agents that regulate cell growth.”

Existing chemical safety tests, which measure the effects of chemicals on human cells, look only at parabens in isolation, he says. They fail to take into account that parabens could interact with other types of signaling molecules in the cells to increase breast cancer risk.

To better reflect what goes on in real life, Leitman and his colleagues looked at breast cancer cells expressing two types of receptors: estrogen receptors and HER2. Approximately 25 percent of breast cancers produce an abundance of HER2, or human epidermal growth factor receptor 2. HER2-positive tumors tend to grow and spread more aggressively than other types of breast cancer.

The researchers activated the HER2 receptors in breast cancer cells with a growth factor called heregulin that is naturally made in breast cells, while exposing the cells to parabens. Not only did the parabens trigger the estrogen receptors by turning on genes that caused the cells to proliferate, but also the effect was significant. The parabens in the HER2-activated cells were able to stimulate breast cancer cell growth at concentrations 100 times lower than in cells that were deprived of heregulin.

The study demonstrates that parabens may be more potent at lower doses than previous studies have suggested, which may spur scientists and regulators to rethink the potential impacts of parabens on the development of breast cancer, particularly on HER2 and estrogen receptor positive breast cells. The findings also raise questions about current safety testing methods that may not predict the true potency of parabens and their effects on human health.

Published on Leave a comment on Report Says Mammograms Haven’t Reduced Rate Of Metastatic Cancer

A report by 3 prominent specialists (including Gilbert Welch - who has been discussed in earlier posts) about trends in metastatic breast and prostate cancer came out today in the New England Journal of Medicine. The biggest finding was that mammograms have not cut the rate of metastatic breast cancer. Mammography screening is based on the hope that cancer that is detected in an early, localized phase can then be treated more easily and that it would reduce the numbers of metastastic cancers (that spread to lymph nodes and to more distant organs) that eventually kill. However, this has not happened.The incidence of metastatic breast cancer has been stable since 1975, and the average age of diagnosis among women older than 40 is still 63.7 years . The authors theorize that "breast cancer is a systemic disease by the time it's detectable". From Medical Xpress:

Study: Mammograms haven't cut rate of advanced breast cancer

A new report raises fresh questions about the value of mammograms. The rate of cancers that have already spread far beyond the breast when they are discovered has stayed stable for decades, suggesting that screening and early detection are not preventing the most dangerous forms of the disease. The report, in Thursday's New England Journal of Medicine, is by three prominent cancer specialists and is based on federal statistics going back to the 1970s.

"We're undergoing what I think for the public is a very confusing debate" about screening, but it's really "a course correction" prompted by more awareness of its risks and benefits to various groups of women, said Dr. H. Gilbert Welch, a health policy expert at Dartmouth Medical School. "All they heard for years was, 'there are only benefits.'" He is the lead author of the report, co-written with Dr. David Gorski of Wayne State University School of Medicine in Detroit and Dr. Peter Albertsen of the University of Connecticut Health Center in Farmington.

"Screening offers hope that cancer can be detected in an early, localized phase when it's more amenable to treatment," they write, but that assumes that cancer starts in one place, grows and then spreads. If that was always true, screening would reduce the rate of advanced cancers. And that has not happened. The rate of breast cancers detected at an advanced stage has been stable since 1975, despite wide use of mammography since the 1980s. The average age of women diagnosed with cancer also has remained around 63, another sign cancers are not being found sooner.

The trends suggest that some breast cancers are already "systemic" or widely spread from the start, and that finding them sooner has limited impact. "Screening mammography has been unable to identify those bad cancers, destined to become metastatic, at an earlier stage. That doesn't say mammography doesn't help less aggressive cancers," but those are less likely to prove deadly, Welch said.

Dr. Barnett Kramer, a screening expert at the National Cancer Institute, said the report shows the limitations of mammography. "I wouldn't want to say it has had no effect but it certainly has not lived up to the anticipated effect," he said. For every tumor detected early because of mammography, "you would hope to see ... an equal reduction in metastatic disease, and that has not occurred."

The situation is very different with prostate cancer. The rate of advanced cases of that disease has been cut in half since screening with PSA blood tests came into wide use around 1988, and the average age at which men are diagnosed has fallen—from 72 to 70, the authors write. However, this does not prove PSA testing is good. Shifting the stage at which a disease is diagnosed is "only the first step for successful screening," which also has to save lives to be worthwhile, Welch said. "Just because you find something earlier doesn't mean you can change its course."

Again, Kramer agreed. Prostate screening, "when put to a definitive test, did not show a clear reduction in prostate cancer mortality" in large, rigorously done trials, he said. The government task force recommends against PSA testing, and says its risks outweigh its benefits for most men.

"Screening is a close call," Welch said. "My guess is few people are helped" by prostate or breast cancer screening while many are harmed by false alarms that trigger unnecessary tests and treatments, he said.

The original report, which also includes a discussion on prostate cancer and the PSA test, in the New England Journal of Medicine:  Trends in Metastatic Breast and Prostate Cancer — Lessons in Cancer Dynamics

Published on Leave a comment on A Viral Cause of Some Breast Cancers?

  This study found something surprising in many samples of human breast tissue - bovine leukemia virus (BLV). Specifically, 59 percent of breast cancer tissue samples had evidence of exposure to BLV (as determined by the presence of viral DNA using modern genetic tests). In contrast, 29 percent of the tissue samples from women who did not have breast cancer (the controls) showed exposure to BLV. Also, BLV was found in 38% of women with premalignant breast tissue changes. The big question: is the bovine leukemia virus somehow leading to breast cancer? That would mean that some breast cancers have a viral origin (and a vaccine can be developed). No one knows this answer, and now more studies need to be done. But....the odds of having breast cancer if BLV was present was 3.1 times greater than if BLV was absent. It also raises the question of whether those women showing exposure with BLV, but currently no breast cancer, are at higher risk for later breast cancer. Stay tuned...  From Medical Xpress:

Virus in cattle linked to human breast cancer

A new study by University of California, Berkeley, researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer. In the study, published this month in the journal PLOS ONE and available online, researchers analyzed breast tissue from 239 women, comparing samples from women who had breast cancer with women who had no history of the disease for the presence of bovine leukemia virus (BLV). They found that 59 percent of breast cancer samples had evidence of exposure to BLV, as determined by the presence of viral DNA. By contrast, 29 percent of the tissue samples from women who never had breast cancer showed exposure to BLV.

"The association between BLV infection and breast cancer was surprising to many previous reviewers of the study, but it's important to note that our results do not prove that the virus causes cancer," said study lead author Gertrude Buehring, a professor of virology in the Division of Infectious Diseases and Vaccinology at UC Berkeley's School of Public Health. "However, this is the most important first step. We still need to confirm that the infection with the virus happened before, not after, breast cancer developed, and if so, how."

Bovine leukemia virus infects dairy and beef cattle's blood cells and mammary tissue. The retrovirus is easily transmitted among cattle primarily through infected blood and milk, but it only causes disease in fewer than 5 percent of infected animals.   A 2007 U.S. Department of Agriculture survey of bulk milk tanks found that 100 percent of dairy operations with large herds of 500 or more cows tested positive for BLV antibodies. This may not be surprising since milk from one infected cow is mixed in with others. Even dairy operations with small herds of fewer than 100 cows tested positive for BLV 83 percent of the time.

What had been unclear until recently is whether the virus could be found in humans, something that was confirmed in a study led by Buehring and published last year in Emerging Infectious Diseases. That paper overturned a long-held belief that the virus could not be transmitted to humans."Studies done in the 1970s failed to detect evidence of human infection with BLV," said Buehring. "The tests we have now are more sensitive, but it was still hard to overturn the established dogma that BLV was not transmissible to humans. As a result, there has been little incentive for the cattle industry to set up procedures to contain the spread of the virus."

The new paper takes the earlier findings a step further by showing a higher likelihood of the presence of BLV in breast cancer tissue. When the data was analyzed statistically, the odds of having breast cancer if BLV were present was 3.1 times greater than if BLV was absent. "This odds ratio is higher than any of the frequently publicized risk factors for breast cancer, such as obesity, alcohol consumption and use of post-menopausal hormones," said Buehring.

There is precedence for viral origins of cancer. Hepatitis B virus is known to cause liver cancer, and the human papillomavirus can lead to cervical and anal cancers. Notably, vaccines have been developed for both those viruses and are routinely used to prevent the cancers associated with them. "If BLV were proven to be a cause of breast cancer, it could change the way we currently look at breast cancer control," said Buehring. "It could shift the emphasis to prevention of breast cancer, rather than trying to cure or control it after it has already occurred."

Buehring emphasized that this study does not identify how the virus infected the breast tissue samples in their study. The virus could have come through the consumption of unpasteurized milk or undercooked meat, or it could have been transmitted by other humans.

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More research support for extra virgin olive oil and the Mediterranean diet being associated with anti-cancer effects, In a study conducted in Spain, women supplementing their diet with extra EVOO (extra virgin olive oil) had a lower incidence of breast cancer after about 5 years.

The Mediterranean diet stresses eating a lot of fruits, vegetables, seeds, nuts, legumes, whole grains, fish, and olive oil.

From Science Daily: Mediterranean diet plus olive oil associated with reduced breast cancer risk

Eating a Mediterranean diet supplemented with extra virgin olive oil was associated with a relatively lower risk of breast cancer in a study of women in Spain, according to an article published online by JAMA Internal Medicine.

The Mediterranean diet is known for its abundance of plant foods, fish and especially olive oil. Miguel A. Martínez-González, M.D., of the University of Navarra in Pamplona and CIBEROBN in Madrid, Spain, and coauthors analyzed the effects of two interventions with the Mediterranean diet (supplemented with extra virgin olive oil [EVOO] or nuts) compared with advice to women to follow a low-fat diet. Study participants in the two intervention groups were given EVOO (one liter per week for the participants and their families) or mixed nuts (30 grams per day: 15 grams of walnuts, 7.5 grams of hazelnuts and 7.5 grams of almonds).

From 2003 to 2009, 4,282 women (ages 60 to 80 and at high risk of cardiovascular disease) were recruited. Women were randomly assigned to the Mediterranean diet supplemented with EVOO (n=1,476), the Mediterranean diet supplemented with nuts (n=1,285) or the control diet with advice to reduce their dietary intake of fat (n=1,391). The women were an average age of 67.7 years old, had an average body mass index of 30.4, most of them had undergone menopause before the age of 55 and less than 3 percent used hormone therapy. During a median follow-up of nearly five years, the authors identified 35 confirmed incident (new) cases of malignant breast cancer.

The authors report that women eating a Mediterranean diet supplemented with EVOO showed a 68 percent relatively lower risk of malignant breast cancer than those allocated to the control diet. Women eating a Mediterranean diet supplemented with nuts showed a nonsignificant risk reduction compared with women in the control group.

The authors note a number of limitations in their study including that breast cancer was not the primary end point of the trial for which the women were recruited; the number of observed breast cancer cases was low; the authors do not have information on an individual basis on whether and when women in the trial underwent mammography; and the study cannot establish whether the observed beneficial effect was attributable mainly to the EVOO or to its consumption within the context of the Mediterranean diet. [The original study.]