Weekly Health Update: soy

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Monday, December 14, 2009

Soy Isoflavones Decrease Breast Cancer Recurrence Risk

Weekly Health Update:

Soy Isoflavones Decrease Breast Cancer Recurrence Risk

"A critical weekly review of important new research findings for health-conscious readers..."

By, Robert A. Wascher, MD, FACS

Updated: 12/13/2009

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author. Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.

Welcome to Weekly Health Update

“A critical weekly review of important new research findings for health-conscious readers”

SOY ISOFLAVONES REDUCE BREAST CANCER RECURRENCE RISK

Regular readers of this column are already aware of the controversy surrounding soy isoflavone intake and breast cancer risk. As happens frequently in clinical research (unfortunately), contradictory research findings have made it difficult to understand the true relationship between dietary soy intake and breast cancer risk (if one exists). There is, for example, both laboratory and clinical data suggesting that a diet rich in soybean-derived products may be associated with a lower risk of developing breast cancer. At the same time, because genistein and other dietary isoflavones are known to weakly mimic the effects of estrogen, there has been some concern that a diet rich in isoflavone “phytoestrogens” may increase both the risk of developing a new breast cancer and the risk of developing a recurrence of a previous breast cancer. (In fact, there is data from laboratory research studies showing that genistein can indeed fuel the growth of human breast cancer cells growing in culture dishes, when exposed to high concentrations of this soy-derived isoflavone.)

A growing body of public health research, primarily from Asian countries where tofu and other soy-based foods are frequently consumed, appears to link increased soy consumption with a decreased lifetime breast cancer risk, particularly when soy-based foods are consumed during adolescence, during the time when development of the female breast is most active (Soy & Breast Cancer Risk). (Interestingly, there is also recent research suggesting that soy products might also reduce the risk of prostate cancer, which is another hormonally driven cancer: Genistein & Prostate Cancer Cells, Dietary Soy & Prostate Cancer Risk.)

Although epidemiological research is, increasingly, suggesting that a diet rich in soybean-derived foods might lower a woman’s lifetime risk of developing breast cancer, many breast cancer experts have remained apprehensive regarding dietary isoflavone intake in women with a prior history of breast cancer, in view of the estrogen-like effects of these “phytoestrogens.” As I have already noted, there is considerable research data available to suggest that soy-derived isoflavones can, at least under certain laboratory conditions, stimulate estrogen-sensitive breast cancer cells to grow and divide. These research findings have left many oncologists feeling uncomfortable in recommending soy-based foods to their breast cancer patients. Now, a newly publish public health study in the Journal of the American Medical Association suggests that soy-based foods may actually reduce the risk of breast cancer recurrence, and death due to any cause, in women who have previously been diagnosed with this very common form of cancer.

In this study, which was performed in Shanghai, China, 5,042 female breast cancer survivors (ages 20 to 75 years) were followed for an average of almost 4 years. All of these patient volunteers underwent detailed surveys regarding their lifestyle habits, including their diets. These patients, who were originally diagnosed with breast cancer between 2002 and 2006, were surveyed at 6, 18, 36 and 60 months following their original diagnosis with breast cancer.

The results of this study indicate that the breast cancer survivors who consumed the greatest amount of soy-based foods in their daily diets were 32 percent less likely to experience a recurrence of their breast cancer when compared to the women who consumed the least amount of soy-based isoflavones. Moreover, the women who consumed the greatest amount of soy were also 29 percent less likely to die, from any cause, when compared to the women who consumed the least amount of soy-derived foods.

A particularly interesting and unexpected finding of this study was that both women with estrogen sensitive breast cancers and women with tumors that were not sensitive to estrogen appeared to experience a significantly decreased risk of breast cancer recurrence if they frequently consumed soy products. Another important finding of this study was that women who were taking the estrogen-blocking cancer treatment drug tamoxifen also appeared to enjoy a reduced risk of breast cancer recurrence with higher levels of dietary soy intake. Additionally, the researchers noted that high levels of soy intake appeared to be about as effective in reducing the risk of breast cancer recurrence as the breast cancer prevention drug tamoxifen, alone.

The results of this very important study mirror the findings of the only other prospective clinical study that has looked at the impact of soy-based foods on breast cancer recurrence (the “Life After Cancer Epidemiology,” or “LACE,” study). The LACE study, which was performed in the United States, followed nearly 2,000 breast cancer survivors for, on average, more than 6 years. In the LACE study, women who were taking tamoxifen, and who also consumed the highest amount of soy-based dietary isoflavones, were 50 percent less likely to develop a recurrence of their breast cancer when compared to women who reported the lowest consumption of soy-derived foods.

As I have pointed out previously, epidemiological research studies based upon dietary surveys are susceptible to several types of bias which, in turn, can cause researchers to draw the wrong conclusions. In this case, however, there are now two large prospective cohort studies that have reached essentially the same conclusions (albeit with a rather limited duration of patient follow-up). Both studies strongly suggest that high levels of soy-based isoflavones in the diet may be able to significantly reduce the risk of breast cancer recurrence. Based upon the findings of this large Chinese study, the apparent cancer risk reduction effect associated with high levels of soy intake also appears to benefit premenopausal and postmenopausal women, as well as women who are taking the estrogen-blocking drug tamoxifen, women with estrogen-sensitive tumors, and women with (counter-intuitively) estrogen-resistant tumors.

In view of the limited duration of patient follow-up in both of these clinical breast cancer studies, as well as the limitations of survey-based epidemiological research in general, I would like to see updated data from both of these studies after at least 10 years of patient observation before I would be willing to tell my breast cancer patients that they should significantly increase their dietary soy intake. On the other hand, the rather compelling data presented by both of these clinical research studies will also make me less anxious when any of my breast cancer patients decide, of their own accord, to increase their intake of soy-derived isoflavones.

Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity

Dr. Wascher is an oncologic surgeon, a professor of surgery, a cancer researcher, an oncology consultant, and a widely published author

(Anticipated Publication Date: March 2010)

(Click above image for TV36 interview of Dr. Wascher)

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Robert A. Wascher, MD, FACS

Dr. Wascher's Archives:

12-6-2009: Salt (Sodium) Intake, Stroke & Cardiovascular Disease

11-29-2009: Exercise & Prostate Cancer Risk

11-22-2009: Genistein (Soy Isoflavone) & Prostate Cancer

11-15-2009: Breast Cancer Treatment & Chronic Pain

1-8-2009: Vitamin D & Breast Cancer Risk

11-1-2009: Exercise & Prostate Cancer Risk

10-25-2009: HPV Virus & Risk of Breast Cancer

10-18-2009: Post-Cholecystectomy Syndrome (Symptoms after Gallbladder Surgery)

10-11-2009: Vitamin D & Falls in the Elderly

10-4-2009: Surgery, NSQIP, Complications & Death

9-27-2009 Stress, Heart Disease, Exercise & Death

9-20-2009: Vitamin D & Colorectal Cancer Survival

9-13-2009: H1N1 Swine Flu Update

9-7-2009: Green Tea, Aging & Lifespan

8-30-2009: Irritable Bowel Syndrome (IBS), Diet & Fiber

8-23-2009: Update on Prostate Cancer and Cryotherapy

8-16-2009: Exercise Improves Lymphedema Symptoms in Breast Cancer Survivors

8-9-2009: Breast Cancer Recurrence, Death & Vitamin D

8-2-2009: Honesty, Dishonesty & Brain Function

7-26-2009: Coronary Artery CT Scans & Cancer Risk

7-19-2009: Hormone Replacement Therapy (HRT) & Ovarian Cancer

7-12-2009: Breast Cancer & Metformin (Glucophage)

7-5-2009: Prostate Cancer & Green Tea

6-28-2009: Air Pollution & the Risk of Deep Venous Thrombosis (DVT)

6-21-2009: Red Yeast Rice, Statins & Cholesterol

6-14-2009: Bone Marrow Stem Cell Transplant & Congestive Heart Failure (CHF)

6-7-2009: Diet, Soy & Breast Cancer Risk

5-31-2009: Diet and Prostate Cancer Risk

5-24-2009: Diabetes, Glucose Control & Death

5-17-2009: Drug Company Marketing & Physician Prescribing Bias

5-10-2009: Hemorrhoids & Surgery

5-3-2009: Statin Drugs & Blood Clots (Thromboembolism)

4-26-2009: Are We Really Losing the War on Cancer?

4-19-2009: Exercise in Middle Age & Risk of Death

4-12-2009: Can Chronic Stress Harm Your Heart?

4-5-2009: Does PSA Testing for Prostate Cancer Save Lives?

3-22-2009: CABG Surgery vs. PCI in Diabetics with Coronary Artery Disease; Sweetened Beverages and Coronary Artery Disease

3-15-2009: Depression, Stress, Anger & Heart Disease

3-8-2009: Coronary Artery Disease: CABG vs. Stents?; Swimming Lessons & Drowning Risk in Children

3-1-2009: Aspirin & Colorectal Cancer Prevention; Fish Oil & Respiratory Infections in Children

2-22-2009: Health Differences Between Americans & Europeans; Lycopene & Prostate Cancer

2-15-2009: Statin Drugs & Death Rates; Physical Activity, Breast Cancer & Sex Hormones

2-8-2009: Hormone Replacement Therapy (HRT) & Breast Cancer; Stool DNA Testing & Cancer of the Colon & Rectum

2-1-2009: Obesity and the Complications of Diverticulosis (Diverticulitis & Bleeding); Obesity, Weight Loss & Urinary Incontinence

1-25-2009: Prostate Cancer, Fatigue & Exercise; Does your Surgeon “Warm-up” Before Surgery?

1-18-2009: Cancer and Vitamins; Teenagers, MySpace and Risky Behaviors

1-11-2009: Exercise Reverses Some Effects of Fatty Meals; Vitamin C and Blood Pressure

1-4-2009: Secondhand Smoke & Heart Attack Risk; Poor Physical Fitness During Childhood & Heart Disease Risk During Adulthood

12-28-2008: Stress & Your Risk of Heart Attack; Vitamin D & the Prevention of Colon & Rectal Polyps

12-21-2008: Breast Cancer Incidence & Hormone Replacement Therapy; Circumcision & the Risk of HPV & HIV Infection

12-14-2008: Vitamin E, Vitamin C and Selenium Do Not Prevent Cancer; Postscript: A Possible Cure for Down’s Syndrome

12-7-2008: Generic vs. Brand-Name Drugs, Stress & Breast Cancer Survival

11-30-2008: A Possible Cure for Down’s Syndrome?; Smoking & Cognitive Decline; Calcium & Vitamin D & Breast Cancer Risk

11-23-2008: Breast Cancer & Fish Oil; Lymphedema after Breast Cancer Treatment; Vasectomy & Prostate Cancer Risk

11-16-2008: Vitamin E & Vitamin C: No Impact on Cardiovascular Disease Risk; Does Lack of Sleep Increase Stroke & Heart Attack Risk in Hypertensive Patients?

11-9-2008: Statins Cut Heart Attack Risk Even with Normal Cholesterol Levels; Statins & PSA Level

11-2-2008: Radiation Treatment of Prostate Cancer & Second Cancers; Sexual Content on TV & Teen Pregnancy Risk

10-26-2008: Smoking & Quality of Life

10-19-2008: Agent Orange & Prostate Cancer

10-12-2008: Pomegranate Juice & Prostate Cancer

10-5-2008: Central Obesity & Dementia; Diet, Vitamin D, Calcium, & Colon Cancer

9-28-2008: Publication & Citation Bias in Favor of Industry-Funded Research?

9-21-2008: Does Tylenol® (Acetaminophen) Cause Asthma?

9-14-208: Arthroscopic Knee Surgery- No Better than Placebo?; A Healthy Lifestyle Prevents Stroke

8-23-2008: Alcohol Abuse Before & After Military Deployment; Running & Age; Running & Your Testicles

8-12-2008: Green Tea & Diabetes; Breastfeeding & Adult Cholesterol Levels; Fish Oil & Senile Macular Degeneration

8-3-2008: Exercise & Weight Loss; Green Tea, Folic Acid & Breast Cancer Risk; Foreign Language Interpreters & ICU Patients

7-26-2008: Viagra & Sexual Function in Women; Patient-Reported Adverse Hospital Events; Curcumin & Pancreatic Cancer

7-13-2008: Erectile Dysfunction & Frequency of Sex; Muscle Strength & Mortality in Men; Cryoablation for Prostate Cancer

7-6-2008: Sleep, Melatonin & Breast Cancer Risk; Mediterranean Diet & Cancer Risk; New Treatment for Varicose Veins

6-29-2008: Bone Marrow Stem Cells & Liver Failure; Vitamin D & Colorectal Cancer Survival; Green Tea & Colorectal Cancer

6-22-2008: Obesity, Lifestyle & Heart Disease; Effects of Lifestyle & Nutrition on Prostate Cancer; Ginkgo Biloba, Ulcerative Colitis & Colorectal Cancer

6-15-2008: Preventable Deaths after Coronary Artery Bypass Graft (CABG) Surgery; Green Tea & Colorectal Cancer; Attention-Deficit/Hyperactivity Disorder (ADHD) & St. John’s Wort

6-8-2008: Vitamin D & Prostate Cancer Risk; Radiofrequency Ablation (RFA) of Kidney (Renal) Cancer; Antisense Telomerase & Cancer

6-2-2008: Acute Coronary Syndrome- Do You Know the Symptoms?; Green Tea & Lung Cancer; Episiotomy & Subsequent Deliveries- An Unkind Cut

5-25-2008: Early Childhood Screening Predicts Later Behavioral Problems; Psychiatric Disorders Among Parents of Autistic Children; Social & Psychiatric Profiles of Young Adults Born Prematurely

5-18-2008: Can Statins Reverse Coronary Artery Disease?; Does Breast Ultrasound Improve Breast Cancer Detection?; Preventive Care Services at Veterans Administration (VA) Medical Centers

5-11-2008: Smoking Cessation & Risk of Death; Childhood Traumas & Adult Suicide Risk; “White Coat Hypertension” & Risk of Cardiovascular Disease

5-4-2008: Super-Size Me: Fast Food’s Effects on Your Liver; Exercise, Weight & Coronary Artery Disease; Contamination of Surgical Instruments in the Operating Room

4-27-2008: Stents vs. Bypass Surgery for Coronary Artery Disease; The “DASH” Hypertension Diet & Cardiovascular Disease Prevention; Testosterone Therapy for Women with Decreased Sexual Desire & Function

4-20-2008: BRCA Breast Cancer Mutations & MRI Scans; Bladder Cancer Prevention with Broccoli?; Diabetes: Risk of Death Due to Heart Attack & Stroke

4-13-2008: Breast Cancer Recurrence & Hormone Replacement Therapy (HRT); Carotid Artery Disease: Surgery vs. Stents?; Statin Drugs & Cancer Prevention

4-6-2008: Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)

3-30-2008: Abdominal Obesity & the Risk of Death in Women; Folic Acid Pretreatment & Heart Attacks; Pancreatic Cancer Regression after Injections of Bacteria

3-23-2008: Age of Transfused Blood & Risk of Complications after Surgery; Obesity, Blood Pressure & Heart Size in Children

3-16-2008: Benefits of a Full Drug Coverage Plan for Medicare Patients?; Parent-Teen Conversations about Sex; Soy (Genistein) & Prostate Cancer

3-9-2008: Flat Colorectal Adenomas & Cancer; Health Risks after Stopping Hormone Replacement Therapy (HRT); Television, Children & Obesity

3-2-2008: Medication & Risk of Death After Heart Attack; Hormone Replacement Therapy (HRT) & Mammogram Results; Selenium: Cancer, Heart Disease & Death

2-23-2008: Universal Healthcare Insurance Study; Glucosamine & Arthritis

2-17-2008: Exceptional Longevity in Men; Testosterone & Risk of Prostate Cancer; Smoking & Pre-malignant Colorectal Polyps

2-10-2008: Thrombus Aspiration from Coronary Arteries; Intensive Management of Diabetes & Death; Possible Cure for Down's Syndrome?

2-3-2008: Vitamin D & Cardiovascular Health; Vitamin D & Breast Cancer; Green Tea & Colorectal Cancer

1-27-2008: Colorectal Cancer, Esophageal Cancer & Pancreatic Cancer: Update from the 2008 American Society of Clinical Oncology's Gastrointestinal Cancers Symposium

1-20-2008: Testosterone Levels & Risk of Fractures in Elderly Men; Air Pollution & DNA Damage in Sperm; Statins & Trauma Survival in the Elderly

1-12-2008: Statins, Diabetes & Stroke and Obesity; GERD & Esophageal Cancer

1-7-2008: Testosterone Supplements in Elderly Men; Colorectal Cancer-- Reasons for Poor Compliance with Screening Recommendations

12-31-2007: Minority Women, Hormone Replacement Therapy & Breast Cancer; Does Health Insurance Improve Health?

12-23-2007: Is Coffee Safe After a Heart Attack?; Impact of Divorce on the Environment; Hypertension & the Risk of Dementia; Emotional Vitality & the Risk of Heart Disease

12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality

12-11-2007: Bias in Medical Research; Carbon Nanotubes & Radiofrequency: A New Weapon Against Cancer?; Childhood Obesity & Risk of Adult Heart Disease

12-2-2007: Obesity & Risk of Cancer; Testosterone Level & Risk of Death; Drug Company Funding of Research & Results; Smoking & the Risk of Colon & Rectal Cancer

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Saturday, November 21, 2009

Genistein (Soy Isoflavone) & Prostate Cancer

Health Report:

Genistein (Soy Isoflavone) & Prostate Cancer

"A critical weekly review of important new research findings for health-conscious readers..."

By, Robert A. Wascher, MD, FACS

Updated: 11/22/2009

GENISTEIN (SOY ISOFLAVONE) & PROSTATE CANCER

While the normal healthy cells within our body are destined to die after a predetermined number of cell divisions (senescence), cancer cells are, essentially, immortal. They divide endlessly, until enough cancer cells have formed to cause a tumor. Similarly the normal cells that line your colon (as well as all of the other estimated 75 trillion cells that make up the human body) never decide to leave the colon and spread to, say, your liver or your lungs. However, colon cancer cells seem to have an overwhelming compulsion to move into blood vessels and lymphatic vessels, and from there, to spread to other distant organs of the body. Once these nefarious pioneers arrive in the liver, the lungs, or in other organs outside of the colon, these metastatic tumor cells then resume their growth cycle, eventually causing metastatic tumors to form. Other types of cancer exhibit the same malignant biology, beginning with invasion through normal tissues, followed by invasion into blood vessels or lymphatic vessels, and ending with the establishment of metastatic colonies of tumors in distant organs and tissues.

This unique, and potentially deadly, biology of cancer cells arises from hundreds, if not thousands, of genetic mutations and other transforming events that occur within cancer cells. As we are still in the infancy of our understanding of the complex biology of cancer cells, we are only beginning to understand the interplay between these hundreds, if not thousands, of aberrations in cancer cell biology.

In most cancer cells, genes that play important roles in normal cell growth and division become corrupted, either due to genetic mutations that cause these “tumor suppressor genes” to become inactivated, or through other so-called “epigenetic” alterations that can also inactivate tumor suppressor genes. One such epigenetic mechanism whereby tumor suppressor genes are commonly inactivated is through “hypermethylation” of the promoter region of the gene. The promoter region of genes can be thought of as a switch that turns on the activation of a gene to produce its specific protein product. Hypermethylation is a process whereby the promoter region of a gene is essentially locked into the “off position.” (When gene hypermethylation occurs, the affected gene is said to be “silenced.”)

Tumor suppressor genes produce proteins that reduce the risk of normal cells becoming cancer cells. Therefore, when key tumor suppressor genes are silenced by hypermethylation, normal (benign) cells may become transformed into malignant cells. This very basic review of the molecular biology of tumor suppressor genes and carcinogenesis is important in order to understand this week’s featured research study.

A tumor suppressor gene known as BTG3 is known to be commonly silenced, by hypermethylation of its promoter region, in cancers of the prostate, breast and kidney. There also is experimental evidence showing that genistein, which is a dietary nutrient found in soybeans and soybean products, can reverse the hypermethylation of multiple different tumor suppressor genes, including BTG3. (Once hypermethylation is reversed, the gene is once again able to produce its cancer-preventing protein.)

A new research study, just published in the journal Cancer, evaluated the effects of genistein on hypermethylated human prostate cancer cells. In this elegant laboratory study, prostate cancer cells were grown in culture dishes, and were tested for hypermethylation of the BTG3 tumor suppressor gene. Once the scientists confirmed that the BTG3 gene was indeed silenced by hypermethylation in these prostate cancer cells, the cells were then treated with genistein. Following additional experiments, the scientists were able to confirm that genistein effectively reversed hypermethylation of the BTG3 tumor suppressor gene. Additionally, a new experimental prostate cancer drug which is being evaluated in ongoing clinical research trials, 5Aza-C, was also tested on the hypermethylated prostate cancer cells, and was found to reverse hypermethylation of the BTG3 tumor suppressor gene, as well.

While it is still a big stretch to assume that the reactivation of the BTG3 tumor suppressor gene in prostate cancer cells growing in a culture dish will translate into clinically meaningful results in human beings, the results of this interesting little study are both intriguing and encouraging. Given that genistein is a natural and generally non-toxic dietary nutrient, it may have certain advantages over the novel prostate cancer drug 5Aza-C (assuming, of course, that ongoing clinical research trials identify a clinical benefit in prostate cancer patients undergoing treatment with 5Aza-C).

The true role of genistein in the prevention and treatment of certain cancers, if any, is not clear at this time. However, the results of this laboratory study add to the growing body of research suggesting that genistein may have clinically significant anti-cancer effects in at least some human cancers.