War on Cancer – 01-2010

by Ralph W. Moss, PhD

Surprising Power of Supermarket Mushrooms

Most readers have heard about the healing powers of exotic medicinal mushrooms, such as reishi, shiitake, and maitake. But what about the white button mushroom (Agaricus bisporus), the kind that is so abundant in American supermarkets? Could they also have anticancer potential? A study performed at City of Hope hospital suggests that they too have anticancer effects if taken daily.

“You don’t need a strong effect to cause cancer prevention,” says said Dr. Shiuan Chen, director of the Division of Tumor Cell Biology at the Beckman Research Institute of the City of Hope, Duarte, California. “Eating 100 grams or even less of mushrooms per day could have an effect on preventing new breast cancers.” Results of Chen’s ongoing study have appeared beginning in 2006 in several leading scientific journals.

Button mushroom extracts turned out to be effective aromatase inhibitors. Aromatase is an enzyme that helps the body make estrogen, a hormone that feeds the growth of breast tumors. Of the seven vegetables tested, button mushrooms had the greatest effect. Other forms of mushrooms (such as portobello, cremini, and shiitake) also proved to be aromatase inhibitors, so one could vary the type eaten to add some variety to the program.

A button mushroom extract reduced the proliferation of breast cancer cells in the laboratory. Giving the extract to mice with breast cancer also suppressed tumor growth. Based on their laboratory experiments, the scientists estimated that 100 grams of mushrooms (less than four ounces) taken per day would help prevent breast cancer growth.

“Results from this and other laboratories support the hypothesis that white button mushrooms may be an important dietary constituent for reducing the incidence of hormone-dependent breast cancer in women,” the authors wrote. “Prevention strategies involving mushrooms are readily available, affordable, and acceptable to the general public.”

Many women who have completed their initial therapy for estrogen-receptor positive (ER+) breast cancer take synthetic drugs for years to inhibit aromatase production. It would be most interesting to see how ordinary mushrooms compare to drugs such as anastrazole (Arimidex) or tamoxifen in their actual anticancer ability. Anastrazole has some potentially serious adverse effects, and so dietary substitutes would be most desirable. But do not be surprised if pharmaceutical companies do not rush to carry out such studies. In 2007, AstraZeneca reported $1.7 billion in sales of Arimidex. This translates into a cost of several hundred dollars per month for women who takes the drug. Four ounces per day of mushrooms will cost about $15 per month. From a drug company’s point of view, the economics simply do not favor such nutritional management.

Comparative studies of the sort that I am proposing are rarely performed and when they do occasionally occur are usually stacked against the less expensive approach. Nor do the authors discuss possible harm from natural or synthetic carcinogens in mushrooms. It would probably be best to seek out organic mushrooms and favor the more flavorful Asian mushrooms, such as shiitake.

Oftentimes, the information we receive about cancer is just plain inaccurate. In fact, you could say that the typical cancer patient is kept in the dark and fed a load of manure … just like the proverbial mushroom.

Will Personalized Oncology Materialize?

The latest buzzword in cancer is “personalized oncology.” This phrase originated mid-decade, in relation to nanotechnology research. But John Niederhuber, MD, director of the National Cancer Institute, gave it currency when he endorsed personalized oncology in his Cancer Bulletin editorial of August 19, 2008. He wrote there about the dawn of a new era of “personalized cancer medicine,” using “specific, targeted therapeutic solutions.”

We are now designing precise therapies to home in on specific targets that result from genomic and functional changes, not only in the tumor cell but also in the tumor microenvironment. … As a result, the future will require innovative strategies and partnerships – between academia, the public sector, and industry – to change the process of determining efficacy and safety, thereby speeding the progress from laboratory to patients” (Niederhuber 2008).

These are fine words. I too believe in personalized oncology, but I also have serious doubts about the commitment of the cancer leadership to pushing this concept. There will be serious resistance at almost every level. Beyond the rather limited testing of breast cancer patients for hormonal and HER2 receptors, I can think of few situations in oncology in which treatment is personalized in any meaningful way for the typical patient. Treatments still seem to be chosen based on predetermined protocols for particular stages of anatomically defined tumors rather than based on individual characteristics of the patient at hand. These protocols in turn are created based on empirical evidence derived from clinical trials. In other words, a particular drug or combination of drugs is favored because on average it performs somewhat better than another combination. The key word here is “average.” There is nothing individual about this approach.

All of this talk about personalized oncology, however, has raised expectations among patients. Writing at Medscape.com, the prominent oncologist Cary A. Presant, MD explains the dilemma that doctors now face:

“The first implication [of personalizing oncology, ed.] is that the way in which we communicate with patients has to change. Because patients are seeing personalized cancer care as a recurring emphasized theme in newspapers and television, it is important for each oncologist to assure patients that their treatment plans are optimized for personalized therapy.”

In other words, oncologists need to reassure their patients that they are indeed getting “the best and most up-to-date care. …” Dr. Presant does not address the question of whether this in fact is true. Dr. Presant also states that surgeons must be informed that fresh tumor tissue removed during biopsies or operations needs to be preserved for microarray DNA testing, “or for cellular essays (for example chemotherapy sensitivity or drug induced apoptosis which can personalize care for patients with leukemia and solid tumors).”

In other words, personalized cancer care often involves the use of cell culture drug resistance testing. It is wonderful to see this recommended in print from such an eminent source. Dr. Presant himself is now working with DiaTech Oncology to bring such tests to consumers. But here’s the problem. Chemosensitivity testing based on apoptosis (programmed cell death) has been around for quite a while. Since the 1980s, it has been denigrated and resisted by the cancer establishment, while it has been championed by less conventional practitioners. The battle has been a bitter one. How then will the cancer establishment suddenly reconcile its new emphasis on personalized oncology with its previous opposition to chemosensitivity tests? This would require NCI, ASCO and the other large cancer organizations to do an about face on an issue which has long divided them from integrative oncologists. Are they about to do so?

Here is how Larry Weisenthal, MD, one of the great pioneers of chemosensitivity testing, summarized the situation earlier this year:

In the late 1980s, the NCI … effectively closed down research into fresh human tumor cell culture methods for testing and optimizing chemotherapy. The proof of this is the complete lack of NIH-funded studies relating to this topic appearing in PubMed for the last 15 years. Instead, we have put all of our clinical trials resources into trying to identify the best treatment for the average patient – in a disease notorious for heterogeneity. … All of a sudden, there is a belated recognition that “personalized” therapy is [a] worthy goal – yet 100 percent of the effort is going into static profiling of molecular markers, as opposed to dynamic, functional profiling of tumor response ex vivo. It’s crazy/nuts, and, down the road, tomorrow’s translational researchers will shake their heads and say “What on earth were they thinking?”

In my opinion, the issue of chemosensitivity testing is a big rock in the road for personalized oncology. Those two words sound great when put together, but the concept is unlikely to be implemented until more influential leaders within the establishment stick their necks out and also point out that the establishment been on the wrong side of this debate for years. Until then, personalized oncology is likely to remain just an attractive slogan rather than a real paradigm shift.

Big Shift on Mammography

Talking about paradigm shifts, on November 16, 2009, the US Preventive Services Task Force (USPSTF) revised its previous position and came out against annual screening mammograms. The new recommendations included the following points:

• Women age 40–49 do not need to receive routine mammograms.

• Postmenopausal women need only get mammograms once every two years, instead of every year, as presently recommended.

• Women over the age of 74 do not need mammograms at all.

• Physicians should stop teaching women to perform breast self-examinations.

These recommendations pertain to the routine screening of the general population and do not apply to the relatively small percentage of women who are known to be at heightened risk of breast cancer.

When you consider how central mammography, as well as breast self-examination or BSE, have been to the “war on cancer,” you realize how drastic a change this represents. The USPSTF is an influential and prestigious group, made up of independent experts in prevention and primary care, appointed by the Department of Health and Human Services.

The backlash against the USPSTF report began immediately. According to a statement by Otis Brawley, MD, chief medical officer of the ACS:

“The American Cancer Society continues to recommend annual screening using mammography and clinical breast examination for all women beginning at age 40.” He claimed that ACS has examined the same data as the USPSTF, and had also looked at additional data that the panel did not consider. Generously, he said that “sensible people” could differ over their interpretation of the data.

Immediately, the report became a Washington political football. The right-wing Heritage Foundation assailed the recommendations as the “Obamacare Rationing Threat to Your Mammograms” (Heritage 2009), while most Democrats also backed away from the report as if it were a pile of overripe Limburger cheese.

HHS Secretary Kathleen Sebelius’ office commissioned the report, yet she said that it had caused “a great deal of confusion and worry” among American women. Therefore it must be wrong! “My message to women is simple. Mammograms have always been an important life-saving tool in the fight against breast cancer and they still are today. Keep doing what you have been doing for years – talk to your doctor about your individual history, ask questions, and make the decision that is right for you.”

Another prominent Democratic politician, Debbie Wasserman Schultz (D-FL), went on the attack:

I am very concerned that these guidelines conflict with many of the well-established recommendations from the American Medical Association, the National Comprehensive Cancer Network, the American Cancer Society, and Susan G. Komen for the Cure. This conflicting information will inevitably lead to confusion among providers and women, resulting in fewer women getting screened for breast cancer.

This is simply an argument from authority. Schultz ignores the fact that many other experts, including the USPSTF panel, disagree with the American Cancer Society on this point, and always have.

I think this controversy throws a light on the much-discussed topic of health-care reform. It is disappointing that there appears to be no mass constituency in the US for cool-headed, rational science, when such findings threaten the fundamental interests of a large portion of the medical establishment. Mammography has apparently become as American as apple pie.

The cochair of the USPSTF said that the recommendations were aimed at reducing the harm caused by overscreening. But the very notion of “overscreening” gets short shrift from the cancer establishment, especially the American Cancer Society (ACS). They have staked their reputation on finding all “cancers” as early as possible, especially through mammography and BSE. Downgrading those recommendations would be too radical a shift for their members.

Almost alone among major organizations, the National Cancer Institute (NCI) valiantly tried to defend the panel’s decisions. In its weekly Cancer Bulletin, it soberly evaluated the new recommendations and commented: “When compared with screening from ages 50 to 69, beginning screening every other year at age 40 produced a small additional reduction in mortality but increased the number of false-positive results by more than 50 percent” (Cancer Bulletin 2009). Robert Aronowitz, MD, of the University of Pennsylvania, pointed out in an op-ed in the New York Times, such recommendations are nothing new. They are the same as most thoughtful experts have been making since the 1970s. “You need to screen 1,900 women in their 40s for 10 years in order to prevent one death from breast cancer,” said Aronowitz, “and in the process you will have generated more than 1,000 false-positive screens and all the over-treatment they entail.” That does not seem like a rational use of scarce medical resources.

References

Adams LS, Phung S, Wu X, Ki L, Chen S. White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice. Nutr Cancer. 2008;60(6):744–756.

Aronowitz R. Addicted to mammograms. New York Times. November 19, 2009. Accessed at: http://tinyurl.com/ybohnks.

Chen S, Oh SR, Phung S, Hur G. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Cancer Res. 2006 Dec 15;66(24):12026–12034.

Heritage Foundation. The Obamacare rationing threat to your mammograms. Morning Bell. November 24, 2009. Accessed at: http://tinyurl.com/ylbco7g.

Hong Y, Chen S. Aromatase inhibitors: structural features and biochemical characterization. Ann N Y Acad Sci. 2006 Nov;1089:237–251. Review.

Niederhuber J. The dawn of personalized oncology. Cancer Bulletin (National Cancer Institute). August 19, 2008. Accessed at: http://tinyurl.com/ybahggd.

Presant GA. Personalized oncology care: a new paradigm for the oncologist and patient. Medscape Hematology/Oncology [free password required]. Sep 4, 2009. Accessed at: http://tinyurl.com/ylqnkqv.

Schrag D, Garewal HS, Burstein HJ, Samson DJ, Von Hoff DD, Somerfield MR. American Society of Clinical Oncology technology assessment: chemotherapy sensitivity and resistance assays. JCO. 2004;22:3631–3638.

Weisenthal L. Cancertest.org [blog]. Accessed at: http://www.cancertest.org/?m=200903.

©2010 by Ralph W. Moss, PhD