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Category: breast cancer

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  In the past few months there has been a lot of discussion about early screening tests for cancer (when there are no symptoms)  versus diagnostic tests (testing once symptoms appear), especially for prostate cancer and breast cancer. Because unfortunately screening also has harms - it is not without significant risks. So the following 2 articles discussing breast cancer are real eye openers. The first article discusses a large study that found that no matter how early the screening and no matter how tiny the cancer and extensive the treatment (e.g, mastectomy of both breasts), in a certain percentage of women the cancer will reappear in a deadly fashion and eventually kill about 3.3% even though they are treated early. The Medscape article points out that it is thought that 28% of early stage breast cancers will progress or reappear as deadly metastatic cancer (even years later) no matter the treatment.

As Dr. Welch has pointed out in his book Overdiagnosis and Less Medicine, More Health - these aggressive cancers are like "birds" - they fly away throughout the body and are deadly no matter when they are diagnosed. A certain percentage of tiny cancers regress (disappear) on their own, others just sit there doing nothing, others grow very slowly (and can be treated successfully when symptoms appear), and then there are those that are so very aggressive that they go throughout the body from the beginning (the birds). And we don't know which will be the aggressive ones when we first find them. So sad..... Meanwhile try to eat healthy foods, get enough sleep, lose weight if overweight, live a healthy lifestyle (don't smoke or drink to excess), and get plenty of exercise in hopes of cancer prevention. I also like to think that each week eating some turmeric (in foods), broccoli famiy foods, olive oil, and berries may also help. Do go read the full original articles. From NY Times:

Early-Stage Breast Condition May Not Require Cancer Treatment

As many as 60,000 American women each year are told they have a very early stage of breast cancer — Stage 0, as it is commonly known — a possible precursor to what could be a deadly tumor. And almost every one of the women has either a lumpectomy or a mastectomy, and often a double mastectomy, removing a healthy breast as well. Yet it now appears that treatment may make no difference in their outcomes. Patients with this condition had close to the same likelihood of dying of breast cancer as women in the general population, and the few who died did so despite treatment, not for lack of it, researchers reported Thursday in JAMA Oncology. 

Their conclusions were based on the most extensive collection of data ever analyzed on the condition, known as ductal carcinoma in situ, or D.C.I.S.: 100,000 women followed for 20 years. The findings are likely to fan debate about whether tens of thousands of patients are undergoing unnecessary and sometimes disfiguring treatments for premalignant conditions that are unlikely to develop into life-threatening cancers.

Diagnoses of D.C.I.S., involving abnormal cells confined to the milk ducts of the breast, have soared in recent decades. They now account for as much as a quarter of cancer diagnoses made with mammography, as radiologists find smaller and smaller lesions. But the new data on outcomes raises provocative questions: Is D.C.I.S. cancer, a precursor to the disease or just a risk factor for some women? Is there any reason for most patients with the diagnosis to receive brutal therapies? If treatment does not make a difference, should women even be told they have the condition?

A majority of the 100,000 patients in the database the researchers used, from a national cancer registry, had lumpectomies, and nearly all the rest had mastectomies, the new study found. Their chance of dying of breast cancer in the two decades after treatment was 3.3 percent, no matter which procedure they had, about the same as an average woman’s chance of dying of breast cancer, said Dr. Laura J. Esserman, a breast cancer surgeon and researcher at the University of California, San Francisco, who wrote an editorial accompanying the study.

The data showed that some patients were at higher risk: those younger than 40, black women, and those whose abnormal cells had molecular markers found in advanced cancers with poorer prognoses. D.C.I.S. has long been regarded as a precursor to potentially deadly invasive cancers, analogous to colon polyps that can turn into colon cancer, said Dr. Steven A. Narod, the lead author of the paper and a researcher at Women’s College Research Institute in Toronto. The treatment strategy has been to get rid of the tiny specks of abnormal breast cells, just as doctors get rid of colon polyps when they see them in a colonoscopy.

But if that understanding of the condition had played out as expected, women who had an entire breast removed, or even both breasts as a sort of double precaution, should have been protected from invasive breast cancer. Instead, the findings showed, they had the same risk as those who had a lumpectomy. Almost no women went untreated, so it is not clear if as a group, they did worse. But some women who died of breast cancer ended up with the disease throughout their body without ever having it recur in their breast — many, in fact, had no breast because they had had a mastectomy. Those very rare fatal cases of D.C.I.S. followed by fatal breast cancer, Dr. Narod concluded, had most likely already spread at the time of detection. As for the rest, he said, they were never going to spread anyway.

Dr. Esserman said that if deadly breast cancers started out as D.C.I.S., the incidence of invasive breast cancers should have plummeted with rising detection rates. That has not happened, even though in the pre-mammography era, before about 1980, the number of women found to have D.C.I.S. was only in the hundreds. Nearly 240,000 women receive diagnoses of invasive breast cancer each year.

Those facts lead Dr. Narod to a blunt view. After a surgeon has removed the aberrant cells for the biopsy, he said, “I think the best way to treat D.C.I.S. is to do nothing." ... Others drew back from that advice.

From Medscape:  The Mystery of a Common Breast Cancer Statistic

A commonly cited breast cancer statistic — that 30% of all early-stage breast cancers will progress, despite treatment, to deadly metastatic disease — appears to have no strong contemporary evidence to back it up. Nonetheless, the statistic appears widely...."It is estimated that 20% to 30% of all breast cancer cases will become metastatic," said the MBCN in response, repeating a statistic from its own website.

The primary source for this declaration is a 2005 CME review on metastatic disease published in the Oncologist by prominent medical oncologist Joyce O'Shaughnessy, MD, from Baylor University in Houston."Despite advances in the treatment of breast cancer, approximately 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent advanced or metastatic disease," Dr O'Shaughnessy wrote.

According to the National Cancer Institute (NCI), the definition of early-stage breast cancer is that which has not spread beyond the breast or the axillary lymph nodes. The range includes stage I, stage IIA, stage IIB, and stage IIIA disease....According to experts, early breast cancers are known to metastasize at 20 years or beyond.

 

Dr Brawley worked with two ACS epidemiologists to examine the issue. They looked at breast-cancer-specific mortality (as identified on death certificates) in 12 health districts in the United States from 2008 to 2012. They were surprised by the finding: "28% of the women who died of breast cancer during that time period had localized disease at diagnosis," said Dr Brawley. The result was unexpected. "We all thought 30% was too high," said Dr Brawley.

(NOTE: Photo credit: Wikipedia Commons of Edouard Manet- Blond Woman With Bare Breasts.)

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A recent report found that when a person is exposed to a little bit (or low doses) of a lot of different commonly encountered chemicals, than the combinations over time may cause changes that increase the risk of cancer (they may initiate cancer). Think about it - we are not exposed to just one chemical at a time (which is how chemicals are tested), but to mixtures or a "chemical soup". It is almost impossible to avoid them. As one of the researchers said: "We urgently need to focus more resources to research the effect of low dose exposure to mixtures of chemicals in the food we eat, air we breathe and water we drink." Testing mixtures of chemicals is currently not required by law.

The effects may be synergistic  - an enhanced effect that is more than the sum of the individual chemicals. And some chemicals may have bigger effects at smaller doses (typical of endocrine or hormone disruptors), than at larger doses - which is not how chemicals are typically viewed (typical view: the more you are exposed to a chemical, the greater the effect). A global task force of 174 scientists looked at 85 common everyday chemicals (at everyday low doses), and 50 were found to support cancer-related mechanisms (processes essential to cancer development). Examples of problematic chemicals that are common in everyday life: triclosan (in many soaps and personal care products), bisphenol A (in many plastics, including can linings), and atrazine (common herbicide or weedkiller). From the LA Times:

Combinations of 'safe' chemicals may increase cancer risk, study suggests

Lots of chemicals are considered safe in low doses. But what happens when you ingest a little bit of a lot of different chemicals over time? In some cases, these combinations may conspire to increase your risk of cancer, according to a new report. “Many [chemicals] have the possibility, when they are combined, to cause the initiation of cancer,” said Hemad Yasaei, a cancer biologist at Brunel University in England, one of the authors of the report. “They could have a synergistic or enhanced effect.”

This is not the way regulators typically think about cancer risk when they evaluate a compound’s safety.Normally, they test an individual chemical on laboratory animals, exposing them to progressively smaller amounts until it no longer causes malignant tumors to grow. Then they take that dose, determine the equivalent for humans, and apply what is called a “margin of safety” by declaring that some small fraction of that low dose is safe for people.

The big assumption driving the margin of safety is that a smaller amount of a chemical is less dangerous than a larger amount. (Think of the familiar axiom, “The dose makes the poison.”) But that’s not true for all chemicals, experts say. Some chemicals, such as those that mimic hormones, may actually be more dangerous at lower doses because the human body is exquisitely attuned to respond to minute amounts of natural hormones such as estrogen and testosterone.

And regulators haven’t required testing of mixtures of chemicals at all...Leroy Lowe, president of Canadian nonprofit Getting to Know Cancer and leader of the report published this week by the journal Carcinogenesis. The new report raises questions about whether this approach is adequate...Humans are exposed to about 80,000 man-made chemicals over their lifetimes, experts say. These chemicals are in the foods we eat, the water we drink and the air we breathe. "We live in a chemical soup,” said toxicologist Linda Birnbaum, director of the National Institute of Environmental Health Sciences, who was not involved in the new study.

The research team — a coalition of 174 researchers from 28 countries — set out to determine whether mixtures of these chemicals, at the very tiny concentrations found in the environment, could plausibly trigger the formation of cancerous tumors. They focused on 85 particular chemicals that were impossible to avoid in modern life, that were likely to disturb biological function and were not thought to pose cancer risks at the very low doses that people tend to ingest them.

The researchers scoured the scientific literature to understand how each of these chemicals could affect 10 important processes that are essential to cancer development. Among them: tumor-promoting inflammation, resistance to cell death and the formation of new blood vessels to feed malignant cells. In addition, they categorized whether each of the chemicals exerted biological effects at very low doses to which humans are ubiquitously exposed. (These doses are so small that they tend to be measured in parts per million or parts per billion.)
Of the 85 chemicals researchers examined, 50 were found to affect cancer-causing processes in the body, even at very low doses.

These 50 everyday chemicals included bisphenol A (used in manufacturing plastics), triclosan (often found in hand sanitizer and anti-bacterial soap) and atrazine (a commonly used herbicide). Since each of these chemicals affects different processes that could lead to cancer — bisphenol A makes cells less sensitive to signals to stop reproducing, for example, while atrazine encourages inflammation — it’s plausible that consuming mixtures of these chemicals is riskier than consuming any one individually.

More details about this report. From Science Daily: Cocktail of common chemicals may trigger cancer

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Again, more research finding that being overweight or obese is associated with an increased risk of breast cancer - specifically higher risk of invasive breast cancer in postmenopausal women. They found that the heavier the woman, the higher the risk, but the risk did not vary with hormone therapy use or race and ethnicity. From Medical Xpress:

Obesity associated with increased breast cancer risk in postmenopausal women

An analysis of extended follow-up data from the Women's Health Initiative clinical trials suggests that postmenopausal women who were overweight and obese had an increased risk of invasive breast cancer compared to women of normal weight, according to an article published online by JAMA Oncology. Obesity is a major public health problem in the United States and obesity has been associated with breast cancer risk in observational studies, systematic reviews and meta-analyses.

The Women's Health Initiative (WHI) protocol measured height and weight, baseline and annual or biennial mammograms, and breast cancer in 67,142 postmenopausal women enrolled from 1993 to 1998 with a median of 13 years of follow-up. There were 3,388 invasive breast cancers. Analysis by the authors found:

  • Women who were overweight (body mass index [BMI] 25 to < 30); obese, grade 1 (BMI 30 to < 35); and obese, grade 2 plus 3 (BMI > 35) had an increased risk of invasive breast cancer compared to women of normal weight (BMI < 25)
  • The risk was greatest for women with a BMI greater than 35; those women had a 58 percent increased risk of invasive breast cancer compared with women of normal weight (BMI < 25)....
  • Obesity was associated with markers of poor prognosis; women with a BMI greater than 35 were more likely to have large tumors, evidence of lymph node involvement and poorly differentiated tumors
  • Women with a baseline BMI of less than 25 who gained more than 5 percent of body weight during the follow-up period had an increased risk of breast cancer....

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This month more research from researcher JJ Goedert about gut microbes in postmenopausal women and breast cancer. Very suggestive research was published September 2014 about the possibility of increasing a person's gut bacteria diversity to lower breast cancer risk. And even earlier research found that the human breast has a microbiome (community of microbes) that is different in healthy breasts as compared to cancerous breasts.

Now JJGoedert and others investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients (before treatment) as compared to 48 control patients (women without breast cancer). The average age of both groups was 62 years.The researchers analyzed the estrogens in the women's urine and the bacterial diversity in fecal samples using modern genetic analysis (such as 16S rRNA sequencing). They found in this study that postmenopausal women with breast cancer had lower gut bacteria diversity and somewhat different composition of gut bacteria as compared to women without breast cancer. They also said that what this means is unknown, that is,"whether these affect breast cancer risk and prognosis is unknown." Some differences in gut bacteria composition: women with breast cancer had lower levels of Clostridiaceae, Faecalibacterium, and Ruminococcaceae; and they had higher levels of Dorea and Lachnospiraceae.

Excerpt is from the Journal of the National Cancer Institute:

Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study.

We investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients, pretreatment, vs 48 control patients. Microbiota profiles in fecal DNA were determined by Illumina sequencing and taxonomy of 16S rRNA genes. Estrogens were quantified in urine....  Compared with control patients, case patients had statistically significantly altered microbiota composition  and lower α-diversity. Adjusted for estrogens and other covariates, odds ratio of cancer was 0.50 per α-diversity tertile. Differences in specific taxa were not statistically significant when adjusted for multiple comparisons. This pilot study shows that postmenopausal women with breast cancer have altered composition and estrogen-independent low diversity of their gut microbiota. Whether these affect breast cancer risk and prognosis is unknown.

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More good news for coffee drinkers! A number of studies have found that coffee drinking is protective against breast cancer (coffee inhibits the growth of tumors), but now research finds it is also protective against breast cancer recurring. The beneficial effects are seen with 2 or more cups of coffee per day. Other studies have found that lifestyle changes (such as weight loss, healthy eating, and exercise) are linked to lower rates of recurrence, but apparently coffee drinking can also be added to the list. This research found that not only is coffee drinking linked to smaller tumors in the first place, but it is also linked to lower rates of recurrence in women also taking tamoxifen. The researchers said: "In summary, this study shows inhibitory effects by caffeine and caffeic acid on breast cancer cell growth." Both caffeine and caffeic acid are present in coffee. From Science Daily:

Coffee protects against breast cancer recurrence, detailed findings confirm

A number of research studies have shown that coffee helps to protect against breast cancer. A new study led by Lund University, has confirmed that coffee inhibits the growth of tumors and reduces the risk of recurrence in women who have been diagnosed with breast cancer and treated with the drug tamoxifen.

The study, which is a follow-up of the results the researchers obtained two years ago, was carried out at Lund University and Skåne University Hospital, in collaboration with researchers in the UK. "Now, unlike in the previous study, we have combined information about the patients' lifestyle and clinical data from 1090 breast cancer patients with studies on breast cancer cells. The study shows that among the over 500 women treated with tamoxifen, those who had drunk at least two cups of coffee a day had only half the risk of recurrence of those who drank less coffee or none at all," explain researchers Ann Rosendahl and Helena Jernström, who obtained the results in collaboration with Jeff Holly and his research team at University of Bristol.

"The study also shows that those who drank at least two cups of coffee a day had smaller tumors and a lower proportion of hormone-dependent tumors. We saw that this was already the case at the time of diagnosis."

In the cell study, the researchers looked more closely at two substances that usually occur in the coffee drunk in Sweden -- caffeine and caffeic acid.

"The breast cancer cells reacted to these substances, especially caffeine, with reduced cell division and increased cell death, especially in combination with tamoxifen. This shows that these substances have an effect on the breast cancer cells and turn off signalling pathways that the cancer cells require to grow.

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Nice summary of cancer prevention advice. What it boils down to is that there is no magic bullet for cancer prevention (maybe the closest thing is to NOT smoke), but it's a lot of little things adding up (your lifestyle) that lowers the risk of cancer. From The Washington Post:

Looking for that fruit or vegetable that might prevent cancer?

Blueberries. Green tea. Tomatoes. And, oh, that cruciferous cauliflower. All make the lists of super foods that might help prevent cancer. Then there are the foods such as smoked meat and fried foods that supposedly might cause cancer. Such information is standard fare for TV doctors and Web sites, but most of us don’t know how to judge such claims. What sounds authoritative may not be. Only about half of the recommendations on two internationally syndicated TV medical talk shows were supported by scientific evidence, according to a recent study in the journal BMJ.

Of course, the blueberries we eat today are good for us. But nutrition’s role in cancer prevention is much more complex than a single dietary component: Evidence has mounted, for example, that lifestyle — diet, weight control and exercise — is vital in helping reduce risk. For now, experts endorse general dietary advice that is healthful for a variety of chronic diseases and conditions, rather than reductionist thinking that focuses on single foods or nutrients.

When you hear that a certain food helps prevent cancer, ask: Which cancer? “Cancer is multiple diseases,” said Marian Neuhouser, a nutritional epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle. Whereas cardiovascular disease might be broken down into several types, including myocardial infarction, stroke and peripheral vascular disease, she said, “for cancer, it’s really over 100 different diseases.” “Cancer is a very complex, very challenging disease to study whether you’re looking at it on the cell level or the clinical level or the epidemiologic and preventive level,” Willett said.

Researchers caution about overreacting to a single study. New findings come out every week, but “we never take any one study to be the answer to anything,” said Nancy Potischman, a nutritional epidemiologist at the National Cancer Institute. Only if the same results come up in multiple studies across multiple populations, “then you might think that, yes, this food might be important,” she said.

Tobacco use remains the leading preventable cause of cancer incidence and death worldwide. After tobacco, the lifestyle trio of diet, weight control and exercise may be linked to one-third to two-thirds of cancers. “They’re inseparable,” Neuhouser said. “You can have a great diet and you can have a healthy weight, but if you’re extremely sedentary then there’s a risk.”And there’s a strong link between excess weight and several kinds of cancer, including the esophagus, breast (after menopause), endometrium, colon and rectum, kidney, pancreas, thyroid, gallbladder, according to the NCI. 

Evidence mounts about how lifestyle may affect risk of cancer. In the largest study of its kind, nearly half a million Americans were evaluated for adherence to American Cancer Society cancer prevention guidelines that include smoking avoidance; a healthful, consistent weight; physical activity; limiting alcohol; and a diet emphasizing plants.

Those who followed the guidelines most closely had lowered risk of developing cancer (10 percent for men, 19 percent for women) and dying from cancer (25 percent for men, 24 percent for women) compared with those whose habits were least in line with the guidelines. Most striking was the reduction of overall risk of dying: 26 percent for men, 33 percent for women during the 14-year study period.

Fourteen types of cancer seemed affected by lifestyle behavior, most particularly gallbladder, endometrial, liver and colorectal. For men and women, a healthful weight and physical activity were the top factors in reduced deaths overall. Albert Einstein College of Medicine Researchers published this analysis online in January in the American Journal of Clinical Nutrition, based on data from a National Institutes of Health/AARP study.

Another approach to cancer and nutrition considers dietary patterns. “What we eat on any one day is not going to change our cancer risk, but it’s the pattern over the long term.” Neuhouser said. Several diets that emphasized fruit, vegetables, whole grains and plants or plant-based proteins were analyzed against information collected over more than 12 years from nearly 64,000 post-menopausal women in the Women’s Health Initiative Observational Study. Consuming a high-quality diet was associated with lower death rates from chronic diseases including cancer, as reported last year in the American Journal of Epidemiology.

The bacteria, viruses and other organisms that live in and on humans seem to play a bigger role in health and disease than was previously understood, Freudenheim said. How the countless microbes in such areas as the gut and the mouth might contribute to or prevent cancers is one of the open questions in the new area of study of the microbiome, which refers to the many organisms in the body, 10 percent of which are human and 90 percent nonhuman.

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This article describes results of a research review showing cancer prevention benefits from eating fatty fish and fish oil. From Science News:

Marked benefits found for cancer prevention with a higher intake of fatty fish

A new research review will once again have people asking for a second helping of wild Alaskan salmon at the dinner table. While several other studies have recently challenged the long-held belief of the benefits of a diet high in omega-3 fatty acids, this new study cites compelling evidence that eating the right kinds of fatty fish, in the right quantity, and prepared the right way, can in fact help prevent the body’s development of adenocarcinomas, a common type of cancerous tumor. A high proportion of the cancers arising in the breast, prostate, pancreas, colon, and the rest of the gastrointestinal tracts are adenocarcinomas.

The authors first cite evidence that the recently-demonstrated ability of daily low-dose aspirin to decrease risk for adenocarcinomas is attributable to its ability to modestly decrease the activity of cyclooxygenase-2 (cox-2), an enzyme which contributes importantly to the genesis and progression of adenocarcinomas. They then propose that an ample dietary intake of omega-3 fats -- the type prominent in fatty fish -- could also be expected to oppose cox-2 activity, and thereby reduce risk for adenocarcinomas.

The authors emphasize that it is not only the amount of fish consumed daily, but also the nature of this fish, and how it is preserved or cooked, that can have a major impact on the potential of dietary fish to lower cancer risk. "An easy way to see the benefit of omega-3 is to look at Italy," Dr. DiNicolantonio said. "The staple oil used in cooking and as a salad dressing in Italy is olive oil, which is quite low in omega-6. Meanwhile, fish -- high in omega-3 -- is a staple food in the Italian diet, and this fish is rarely salt-preserved or fried. In Italians studies, subjects who consumed fish at least twice weekly as compared to those who ate fish less than once a week, were found to be at a significantly lower risk for a number of cancers, including ovarian, endometrial, pharyngeal, esophageal, gastric, colonic, rectal, and pancreatic."

The authors also focus on several recent studies in which regular consumption of fish oil is correlated with lower subsequent cancer risk. These studies have reported lower risks for colorectal, breast, and advanced prostate cancer in those taking such supplements. And a recent study from the University of Washington, which estimated total omega-3 intakes of its subjects from both fish and from supplements, found that a high omega-3 intake was associated with a 23 percent reduction in total cancer mortality. Indeed, mortality from all causes was significantly lower in those with higher omega-3 intakes. The authors also noted that cox-2 is significantly expressed in pre-malignant and early stage adenocarcinomas, but expression is sometimes lost as cancers mature. This may be why cox-2 inhibition (via increased omega-3 intake) seems to have greater potential for cancer prevention, than for cancer therapy.

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The following medical article (actually an interview with Prof. Cedric F Garland, Department of Family & Preventive Medicine, University of California San Diego School of Medicine) is strongly in favor of Americans getting their Vitamin D levels tested, and taking vitamin D3 (if needed) to raise serum levels of vitamin D's metabolite 25(OH)D to at least 30 ng/mL and preferably more.

It is suggested that taking 1000 IU of vitamin D3 daily would achieve these levels in most people. From Medscape:

Vitamin D and Mortality Risk: Should Clinical Practice Change?

Traditionally associated with skeletal disease including osteoporosis and fractures, low levels of serum 25-hydroxyvitamin D (25[OH]D), the metabolite usually measured as a mark of vitamin D status, more recently have been linked to a wide range of nonskeletal diseases, including some cancers and autoimmune, cardiometabolic, and neurologic diseases. A number of studies also have reported an inverse association between 25(OH)D concentration and all-cause mortality.

To explore this association more, Medscape reached out to Dr. Cedric Garland, a well-known expert on vitamin D. Dr. Garland is a professor in the Division of Epidemiology, Department of Family and Preventive Medicine, and a Fellow of the American College of Epidemiology. He has a Doctor of Public Health degree from University of California San Diego and studied epidemiology at Johns Hopkins. His research has focused on vitamin D status in health and the association between vitamin D deficiency and increased risk for disease, including some common cancers (breast cancer, colon cancer, leukemia, and melanoma) and diabetes. He is active in seeking to reduce the risk for cancer and diabetes by improving vitamin D status among the US population.

To examine the relation between serum 25(OH)D and mortality, Dr. Garland and colleagues at the University of California San Diego and others in the United States pooled data from 32 studies published between 1966 and 2013.[6] They found an overall relative risk of 1.8 (95% confidence interval [CI]: 1.7-1.8; P <.001) comparing the lowest (0-9 ng/mL) with the highest (>30 ng/mL) category of 25(OH)D for all-cause mortality. Serum 25(OH)D concentrations ≤30 ng/mL were associated with higher all-cause mortality than concentrations >30 ng/mL (P <.01).

The investigators noted that these findings confirmed observations from the Institute of Medicine (IOM) that 25(OH)D levels of <20 ng/mL are too low for safety,[8] but they suggested a cut-off point of >30 ng/mL rather than >20 ng/mL for all-cause mortality reduction. This level "could be achieved in most individuals by intake of 1000 IU per day of vitamin D3," the investigators said, noting that this is described as a safe dose in almost all adults by both the IOM[8] and Endocrine Society[9] clinical guidelines on dietary intake of vitamin D.

In particular, a randomized clinical trial by Lappe et al[12] had demonstrated a reduced risk for all cancers with vitamin D supplementation in postmenopausal women.... Only one third of the US population is below 20 ng/mL,[15] but two thirds of the population is below 30 ng/mL.[16]

We decided to look at what would happen if we put together all the existing studies that have looked at the survival of "ordinary" people; that is, mostly people in general practices who did not, for the most part, have illnesses. Studies that only included people who were already ill were not eligible for inclusion in our analysis. We found 88 relevant studies, of which 32 presented their data by quartiles of intake, allowing us to see a dose response

The incidence of colon cancer is very high in countries like Iceland and Sweden, and other countries nearer the North Pole, and in countries like New Zealand, which is closer to the South Pole, and intermediate in countries at intermediate latitudes such as the United States, which is, on average, 38º north of the Equator. By the time you get down within the tropics, which is 23º from the Equator, it begins to decrease, and within 5º of the Equator there are vanishingly low incidence rates of colon cancer. In the past, some scientists theorized that the low incidence rates near the equator were due to intake of a high-fiber diet, but now my group believes -- and many others are leaning more in this direction -- that it is the high UVB irradiance and high circulating 25(OH)D year-around nearer the equator rather than a high-fiber diet that best explains the inverse association with solar UVB irradiance

Raising the serum 25(OH)D from 30 to 40 ng/mL reduces the incidence of breast, bowel, and lung cancer by 80%, as reported by Lappe and colleagues in their clinical trial.[12]On the other hand, if you lump all cancers together, in both sexes, and include countries where there is a whole lot of cigarette smoking, then you may obscure the effect of the vitamin D. Vitamin D is not able to overcome the effect of heavy smoking, and the CHANCES analysis[7] included data from people in countries like the Czech Republic, Poland, and Lithuania, where there is a huge amount of smoking. Although the effects are still there, they are weakened.

Studies such as our meta-analysis have provided us an opportunity to not just be locked into the present but to predict mortality on the basis of vitamin D levels in the present. I had expected our results to be convincing, but we were shocked at the persistence of the belief that very low levels of vitamin D, such as approximately 20 ng/mL, are safe. They are not safe with regard to breast and colon cancer, several other cancers, diabetes in youth and adulthood, fractures, and other complications of 25(OH)D <30 ng/mL. Even higher levels, such as 40-60 ng/mL, would be even safer, according to a letter of consensus of expert vitamin D scientists and physicians.

In addition, 2 ongoing trials, the CAPS study[23] (aiming to replicate the findings of Lappe et al[12]) and the VITAL study,[22] are both using a vitamin D3 dose of 2000 international units (IU)/day. I think that if I were to design a trial, knowing what we know today, I would use 4000-5000 IU/day. It seems as though each time we do a clinical trial, by the time the trial is completed, we know that the doses were too small to elicit an effect.

I am also concerned that there may be not enough calcium to see an effect. In CAPS, the women are being given 1500 mg of calcium, which was done in the original randomized controlled trial in which 80% of the cancers in postmenopausal women were prevented. I would have stayed with this design and dose for the VITAL trial. We know that it helps because in their original trial, Lappe and colleagues[12]examined the effects of vitamin D alone vs vitamin D plus calcium, and the effects were stronger when the calcium was included.

Testing should be universal. And ideally it should be done in March when the vitamin D is at its lowest levels. This will prevent hundreds of thousands of cases of serious diseases worldwide annually, beginning with postmenopausal breast cancer and including colon cancer and types 1 and 2 diabetes. Skipping this test would be equivalent to not measuring blood pressure, serum lipids, or weight at an annual exam.

No one should run a serum 25(OH)D less than 30 ng/mL. This means that two thirds of the US population needs supplementation. You may have noticed that President Obama was recently tested for his vitamin D, and it was 22.9 ng/mL.[35] His physicians wisely decided to treat him, and he is now taking vitamin D.

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Amazing possibilities, but more studies needed. The key finding: A diversity of the bacterial community in the gut is good, and perhaps can be altered through diet, and so perhaps alter the future risk of developing breast cancer.From Science Daily:

Diverse gut bacteria associated with favorable ratio of estrogen metabolites

Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to a new study.

Since the 1970s, it has been known that in addition to supporting digestion, the intestinal bacteria that make up the gut microbiome influence how women's bodies process estrogen, the primary female sex hormone. The colonies of bacteria determine whether estrogen and the fragments left behind after the hormone is processed continue circulating through the body or are expelled through urine and feces. Previous studies have shown that levels of estrogen and estrogen metabolites circulating in the body are associated with risk of developing postmenopausal breast cancer.

"In women who had more diverse communities of gut bacteria, higher levels of estrogen fragments were left after the body metabolized the hormone, compared to women with less diverse intestinal bacteria," said one of the study's authors, James Goedert, MD, of the National Institutes of Health's National Cancer Institute (NCI) in Bethesda, MD. "This pattern suggests that these women may have a lower risk of developing breast cancer."

As part of the cross-sectional study, researchers analyzed fecal and urine samples from 60 postmenopausal women enrolled in Kaiser Permanente Colorado. .

"Our findings suggest a relationship between the diversity of the bacterial community in the gut, which theoretically can be altered with changes in diet or some medications, and future risk of developing breast cancer," Goedert said. 

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Excellent way to lower breast cancer risk. From Science Daily:

Postmenopausal breast cancer risk decreases rapidly after starting regular physical activity

Postmenopausal women who in the past four years had undertaken regular physical activity equivalent to at least four hours of walking per week had a lower risk for invasive breast cancer compared with women who exercised less during those four years, according to new data.

"Twelve MET-h [metabolic equivalent task-hours] per week corresponds to walking four hours per week or cycling or engaging in other sports two hours per week and it is consistent with the World Cancer Research Fund recommendations of walking at least 30 minutes daily," said Agnès Fournier, PhD, a researcher in the Centre for Research in Epidemiology and Population Health at the Institut Gustave Roussy in Villejuif, France. "So, our study shows that it is not necessary to engage in vigorous or very frequent activities; even walking 30 minutes per day is beneficial."

Postmenopausal women who in the previous four years had undertaken 12 or more MET-h of physical activity each week had a 10 percent decreased risk of invasive breast cancer compared with women who were less active. Women who undertook this level of physical activity between five and nine years earlier but were less active in the four years prior to the final data collection did not have a decreased risk for invasive breast cancer

"We found that recreational physical activity, even of modest intensity, seemed to have a rapid impact on breast cancer risk. However, the decreased breast cancer risk we found associated with physical activity was attenuated when activity stopped. As a result, postmenopausal women who exercise should be encouraged to continue and those who do not exercise should consider starting because their risk of breast cancer may decrease rapidly."

Fournier and colleagues analyzed data obtained from biennial questionnaires completed by 59,308 postmenopausal women who were enrolled in E3N, the French component of the European Prospective Investigation Into Cancer and Nutrition (EPIC) study. The mean duration of follow-up was 8.5 years, during which time, 2,155 of the women were diagnosed with a first primary invasive breast cancer.