EPIGENETICS for Breast Cancer Prevention

Life Extension Magazine

Life Extension Magazine November 2012

by Alexander Johnson

Every year, nearly 250,000 women learn that they have invasive breast cancer. Roughly 58,000 more will be diagnosed with early cases of the disease.1 And about 40,000 will die.2 Some women are so paralyzed by the fear of this disease that they undergo double mastectomies in a drastic attempt to prevent it from occurring. Despite these dire numbers and drastic actions, there is hope for the prevention of breast cancer. And it doesn't come in the form of risky surgical procedures—it comes from nature itself. Up to 50% of breast cancer cases are now thought to be preventable through simple changes in diet and lifestyle.3,4 The use of specific agents to prevent cancer from developing is called chemoprevention. Utilized properly, chemoprevention should be able to eliminate pre-malignant cells, block the progression of normal cells into invasive tumors, and ultimately stop a cancer before it ever reaches a size that could cause symptoms or be detected.5 Research has demonstrated that there are scores of nutrient molecules with potent, and often multiple chemotherapeutic effects. For example, calcium, selenium, and vitamin D have all shown some effect in reducing cancer occurrence.6 An even larger array of nutrients is responsible for changes that promise powerful chemoprevention against breast cancer.7 In this article we'll explore some of the most exciting implications of the power of nutritional supplementation to prevent breast cancer. Then we'll give you a rundown of nearly three dozen specific nutrients that hold out special hope in the fight against this epidemic killer. Revolutionary New Science Holds The Key to Breast Cancer Prevention A relatively new science called epigenetics has shed light on the enormous control we as individuals have on whether or not we develop cancer. The science of epigenetics is the study of long-lasting changes in gene function that do not involve changes in gene structure.9 Epigenetics has taught us that we can use factors such as nutrients to turn a gene on and off.10 If the gene that's activated is a tumor-suppressor gene (a gene that prevents excessive cell replication), or one that triggers termination of defective cells (such as pre-malignant cells through normal apoptotic processes), these epigenetic modifications are capable of blocking the progression of a cancer cell.10 The science of epigenetics has finally explained how nutrients and certain drugs can change the way breast cancer cells age and reproduce.9 Based on the science of epigenetics, Big Pharma is now racing to produce chemopreventive drugs.7 But nature is far ahead, as usual. Scores of researched nutrients have potent, and often multiple, epigenetic and chemotherapeutic effects (Table 1)—without the side effects associated with drugs like tamoxifen, which the FDA approved for breast cancer prevention. In the next section, we'll look at nature's most powerful chemopreventive nutrients (and a few drugs), how they work, and what they may mean for the future of breast cancer.11 TABLE 1. Risk Reduction for Breast Cancer By Specific Compounds Nutrient Reduction in Breast Cancer Risk Aspirin 20-32%62,66,146 Coffee 40%147 Conjugated Linoleic Acid 60%148 Fish Oil, Omega-3 Fats 73-81%149 Green Tea 22-48%150-152 Lycopene 40-68%153-155 Melatonin 38%156 Metformin 23-56%157,158 Resveratrol 61%159 Soy & Soy Isoflavones 18-92%160-162 Vitamin D 11-44%87,163 Nature's Cancer-Preventing Nutrients What follows are 11 categories of targeted nutrients that have been studied for their impact on breast health and cancer prevention. You can choose what combination of nutrients would be most effective for your situation. At the end of this report is a dosing table. Most of the nutrients in this list have multiple ways in which they help to prevent cancer. That's because each individual nutrient has many different biochemical targets in breast cancer prevention. Because cancer has multiple causes and phases of development, scientists are well aware that a multi-targeted approach is the best way to attack a disease like cancer.   1. Nutrients that Prevent DNA Damage Breast cancer, like all others, invariably begins with some change to the DNA structure or function of an individual cell. Both DNA damage and a change in the way a normal gene is expressed can trigger a cell to become malignant. In either case, a tumor suppressor gene can become silenced, allowing unregulated cell replication, or a tumor promoter gene can become activated. However, many nutrients work to prevent the DNA damage that can lead to a cell becoming cancerous. The list of nutrients proven to have anti-breast cancer effects is long, a tribute to the role of oxidant damage in breast cancer formation. Antioxidant nutrients proven to have anti-breast cancer effects include: Coenzyme Q10 (CoQ10)14-17 Coffee and many of its constituents18-20 Curcumin21-23 Green tea polyphenols, especially epigallocatechin gallate (EGCG)24 Indole-3-Carbinol (I3C)25 Lycopene26,27 Melatonin28 Metformin29 N-acetylcysteine (NAC)30-35 Pomegranate juice and extracts36-38 Resveratrol39 Selenium40 Silibinin and silymarin21,41-47 Soybean flavonoids genistein and diadzein 40,47 Sulforaphane48 Tocotrienols49-53   2. Nutrients that Control Regulatory Genes Processes called hypermethylation and histone deacetylation can unlock undesirable epigenetic expression or suppress regulatory genes. Fortunately, a number of nutrients block these processes, and therefore can help to prevent the epigenetic changes that lead to breast cancer. These include:7,11 Omega-3 fatty acids from fish oil54 Lycopene55 Genistein, a soy isoflavone55 Resveratrol56,57 Caffeic acid, a component of coffee19 Sulforaphane from cruciferous vegetables10,58,59 How Starch and Fiber Differ— And Why it Matters to You Breast cancer threatens the lives of millions of women. Breast cancer is caused by a complex interaction of multiple dietary, lifestyle, environmental, and genetic factors. The science of epigenetics, the study of how genes can be expressed differently without changes in actual gene structure, has provided profound new insights into breast and other cancers. A large number of nutrients have now been found to exert favorable epigenetic effects on breast cancers from the moment a cell undergoes malignant transformation through the fully-developed tumor's attempts to invade and metastasize. Nutrient-based epigenetic chemoprevention represents an entirely new front in the battle against breast cancer.   3. Nutrients that Fight Cancer-Promoting Inflammation Once a cell has become malignant, inflammation is a powerful epigenetic promoter of the next steps in the process of cancerous transformation.60 Nature provides many natural anti-inflammatory molecules with specific promise in breast cancer chemoprevention, including the following: Acetylsalicylic acid (aspirin)61-66 Conjugated linoleic acid (CLA)67,68 Coffee compounds18,69 Curcumin70,71 Omega-3 fatty acids EPA and DHA from fish oil72 Pomegranate extracts73 Quercetin74 Resveratrol39 Vitamin D75   4. Nutrients that Block Excessive Cell Replication The excessive rate of cell replication is one of cancer's best-known features. Many nutrients are capable of blocking the continuous churning of the cellular replication cycle and slowing or stopping cancer growth, which ultimately contributes to breast cancer chemoprevention through epigenetic means. These include: Apigenin, a yellow flavone molecule found in many plants76 Aspirin77 Coffee components78 Indole-3-Carbinol (I3C) from cruciferous vegetables79,80 Melatonin81 Pterostilbene, a close relative of resveratrol82 Selenium83 Sulforaphane from cruciferous vegetables10,84   5. Nutrients that Transform Malignant Cells Back into Healthy Ones Breast carcinoma Even after cells have undergone malignant transformation, there's a chance to reverse that process by forcing them to "differentiate" back into normal tissue-forming cells. Nutrients that promote the differentiation of breast cancer cells include: Conjugated linoleic acid (CLA)85 N-acetylcysteine (NAC)32 Vitamin D86,87   Breast Cancer Facts Breast cancer is the most common cancer among women in Western countries.12-13 It takes a greater toll on women 40 or older, among whom 95% of new cases and 97% of deaths occur. The median age at breast cancer diagnosis is 61 years. The peak incidence of the disease occurs between ages 75 and 79, with 421 new cases per 100,000 women.1   6. Nutrients that Trigger the Death of Cancer Cells A powerful natural means of controlling cell replication is the process of apoptosis, or programmed cell death. Normal cells have the ability to self-destruct if they receive signals that they are replicating too rapidly. Malignant cells lose this ability, contributing to their overwhelming growth rate. A number of nutrients have the ability to restore breast cancer cells' ability to die by apoptosis, including the following: Apigenin76,88,89 Coffee compounds78 Conjugated linoleic acid (CLA)90 Curcumin91,92 Green tea polyphenols and EGCG24 Indole-3-Carbinol (I3C)79,93 Melatonin94 N-acetylcysteine (NAC)95 Pomegranate96,97 Quercetin98 Selenium83 Silibinin99 Soy Isoflavones97,100,101 Tocotrienols102,103 Vitamin D94   7. Nutrients that Restore Receptors that Enhance Standard Treatments Roughly 70% of breast cancer cells depend on a continuous supply of estrogen for their growth, while a smaller number of cancers depend on the growth factor called HER2/neu. These cancers can potentially be treated by interfering with the receptors, making them (at least in theory) less dangerous. Between 15 and 25% of breast cancers, however, are so-called "triple-negative" cancers, meaning that they lack any of the three receptors (estrogen, progesterone, or HER2/neu), and are correspondingly resistant to treatment. Among the most exciting discoveries in the epigenetics of nutrients for cancer chemoprevention is that many nutrients can restore one or more of those receptors to the surface of breast cancer cells, lowering the bar to effective standard treatments such as the estrogen receptor blocker tamoxifen.15 Other nutrients can modify at least one of the receptors, impairing the cells' ability to receive the growth signals they require, and triggering their early death. Nutrients (and a drug) capable of epigenetic chemoprevention through modification or restoration of breast cancer receptors, or which have effectiveness against triple negative cancers include: Coffee104,105 Conjugated linoleic acid (CLA)106 Curcumin107 Green tea polyphenols11,108 Melatonin109 Metformin110 Omega-3 fatty acids from fish oil111 Sulforaphane from cruciferous vegetables11,112   8. Nutrients that Inhibit Estrogen Production The enzyme aromatase is responsible for producing estrogen in body tissues, including breast cells. Therefore, inhibiting aromatase activity is an important means of slowing the growth of the 70% of estrogen-dependent breast cancers. Nutrients capable of chemoprevention through aromatase inhibition include: Chrysin113 Enterolactone from lignan extract114 Grape seed extract115 Hops extracts116 Melatonin109 Pomegranate117 Vitamin D75 Note: aromatase inhibiting drugs like Arimidex® (anastrozole) have far more potent estrogen-suppressing effects, but they lower estrogen so much that they can induce severe menopausal effects.   9. Nutrients that Block Abnormal Growth Factors In addition to estrogen, progesterone, and HER2/neu, a number of other growth factors act on breast cancer cells. Inhibition or epigenetic modification of these growth factors is a major target in breast cancer chemoprevention, especially by the following nutrients: Apigenin118 Conjugated linoleic acid (CLA)119 Curcumin92 Gamma tocotrienol120 Green tea polyphenols108,121 Indole-3-Carbinol (I3C)80 Melatonin94 Omega-3 fatty acids111 Silibinin41 Sulforaphane59 Vitamin D94 Breast Cancer: The Basics Growing tumor By the time breast cancer is detectable, it has already gone through a lengthy and complex series of events that turned a normal, healthy cell into a cancerous one. Basically, cancer occurs when cellular replication has gone awry.8 In a healthy body, excess cell replication is under tight control by genetic signals from genes called tumor suppressor and suicide genes.5 When a tumor suppressor gene is turned on in response to an abnormal signal, it prevents cell division from getting out of control. Similarly, the activation of a suicide gene triggers a programmed form of cell death called apoptosis. Ultimately, the development of cancer is the direct result of how genes express themselves in tissues. Cancers form when the function of a gene changes—either activating cancer-producing genes, or deactivating cancer-suppressing genes.7

10. Nutrients that Cut Off the Blood Supply to Growing Tumors Once a cancer has begun its rapid growth phase, it requires a vast increase in its blood supply. Tumor cells are capable of inducing new blood vessel growth (angiogenesis) through multiple epigenetic mechanisms. A number of nutrients are capable of reversing that process and depriving growing tumors of blood supply. These include: Apigenin122-124 Coenzyme Q10 (CoQ10)17,125 Coffee diterpenes18 Conjugated linoleic acid (CLA)85 Curcumin126 Grape seed extract127,128 Green tea129,130 Indole-3-Carbinol (I3C)79 Lycopene27 Melatonin27 N-acetylcysteine (NAC)30,33,34 Omega-3 fatty acids131 Pomegranate132 Quercetin74 Silibinin133 Soy isoflavones134-136 Vitamin D75,86   11. Nutrients that Prevent Tumors from Spreading Growing tumor Growing tumors develop the ability to invade local and regional tissues, and to "seed" other body areas with malignant cells through the process of metastasis. To accomplish these processes, tumors increase their production of "protein-melting" enzymes called matrix metalloproteinases, or MMPs. Effective chemoprevention involves epigenetic changes that impair tumors' production of MMPs, as is seen in the activities of these nutrients (and drugs): Coenzyme Q10 (CoQ10)137 Coffee diterpenes and phenolics18,138 Conjugated linoleic acid (CLA)139 Cruciferous vegetable components sulforaphane and isothiocyanates140 Curcumin141 Green tea polyphenols24, 121,130 Melatonin142 N-acetylcysteine (NAC)31 Silibinin41,42,133 Soy isoflavones101,135 Compounds that function via other mechanism to inhibit metastasis include: Modified citrus pectin143+ Aspirin144 Cimetidine145+ +Note that cimetidine and modified citrus pectin are only used by those with existing cancers. They have not shown preventive effects. Summary Breast cancer, the leading malignancy among women, has long evaded attempts at prevention. However, breakthroughs in the science of epigenetics has led both to a greater understanding of how breast cancer forms—and ultimately to the discovery of novel approaches to chemoprevention. A large number of nutrients are capable of beneficial epigenetic modifications in breast cancer cells. These nutrients are capable of impeding breast cancer initiation, promotion, proliferation, invasion, and metastasis. They accomplish these multiple effects through the activation of genes that suppress cancer, the deactivation of genes that promote cancer, the promotion of cancer cell death through apoptosis, the modification of hormonal and other growth factor receptors, and fundamental effects such as antioxidant and anti-inflammatory actions. With the broad range of breast cancer chemoprevention available through nutrient supplementation, it only makes sense to include a wide variety of these supplements in your health promotion regimen. 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