NEW BREAST CANCER PROTOCOL

Please read this before continuing on:

After years of FDA suppression, effective alternative therapies are coming out of the closet.

The very words strike fear in any woman. Most women know either a friend or a relative who has or has had breast cancer-one in eight women are struck with the disease. In light of potential disfiguring surgery and the possibility of metastatic spread and death, the disease's impact on women cannot be understated.

Breast cancer has become the second largest cause of cancer death in women, after lung cancer, and the leading cause of death for women between the ages of 35 and 54. According to the American Cancer Society, more than 173,000 women will be diagnosed with breast cancer in the coming year; about 43,000 will die from it. Clearly, we are in the midst of a breast cancer epidemic. This protocol will deal with the treatment of breast cancer and will also contain information for the prevention of the disease.

Introduction
Similarly to most other cancers, once breast cancer has been detected there is already the chance that the disease has spread. Once a lump has been discovered on the breast or even discovered early on a mammogram, there may already be an average of 45 billion cancer cells present, and some of these malignant cells may have metastasized to other parts of the body. As in other types of cancer, conventional medicine stages the disease based upon factors such as tumor size, presence of lymph node involvement or distal spread. Depending upon the stage, the oncologist may recommend a number of options and combinations ranging from simple lumpectomy to complete mastectomy, radiation and chemotherapy.

As discussed in the Foundation's Cancer Protocol, most physicians practicing complementary medicine believe the net effect of radiation and chemotherapy weakens the very system that protects us from cancer in the first place, the immune system. This leaves the cancer patient more vulnerable to the development of metastatic lesions in critical organs of the body. Despite this immune-suppression effect, studies demonstrate that radiation and chemotherapy can improve survival in breast cancer patients when appropriately used. The authors of this protocol and the Life Extension Foundation cannot overemphasize the need for the breast cancer patient to become as well informed as possible regarding the disease, and to be under the care of an oncologist who specializes in the treatment of breast cancer. Only then can a patient make informed decisions regarding the appropriate therapies to utilize.

Diet
Although there has been some controversy regarding the association between types of dietary fat and the development of breast cancer, some suggestions can be made. The American diet, particularly in the last 15 years with the push for higher consumption of carbohydrates and the robust incorporation of fat, is most likely associated with the development of breast cancer. One reason may be that a high fat and carbohydrate diet increases the development of so-called free radicals that cause tissue damage and can affect cell development, the immune system, and hence lead to the propensity to develop cancer in general. Additionally, carbohydrates with a high glycemic index (meaning they are quickly converted to glucose) cause the release of insulin, resulting in rapid fluctuations in glucose levels that may have an impact on the development of breast cancer. Therefore, breast cancer patients should markedly decrease their intake of both saturated and unsaturated fats and simple carbohydrates containing a high glycemic index.

Hormonal manipulation
Although the cause of breast cancer has not been found, it has become clear that hormonal manipulation may have a therapeutic impact upon the course of the disease. This is why tumors, when removed during surgery, are studied to find out whether or not they are so-called estrogen-receptor positive or negative. If the cancer is estrogen-receptor positive, theoretically there should be a response to manipulation of estrogen. This is exactly the role tamoxifen has played as an adjuvant drug therapy in the treatment of the disease. However, studies have demonstrated that after two years, tamoxifen can cause an increase of estrogens in the blood. This is one reason that breast cancer cells may become resistant to tamoxifen treatment. Another reason for tamoxifen failing to control cell proliferation is that estrogen-receptor positive cells often mutate into a cancer cell type that does not need estrogen to proliferate. Tamoxifen can cause serious side effects after two years and for this reason it has been suggested that tamoxifen treatment not go beyond a two-year time period. Those using tamoxifen should also follow the Foundation's Anti-Thrombosis Prevention protocol because tamoxifen and cancer itself can increase the risk of abnormal blood clots.

Vitamin D3 and melatonin have been shown to synergistically enhance the beneficial effects of tamoxifen, and for this reason, women taking tamoxifen should also take 4000 to 6000 IU of vitamin D3 and 3 to 50 mg of melatonin nightly. While tamoxifen's side effects may limit its use to two years, most people can take melatonin and moderate doses of vitamin D3 indefinitely. A few people experience kidney toxicity and abnormal calcium metabolism when taking high doses of vitamin D3, and breast cancer patients are also at a high risk for developing blood calcium disorders. For all these reasons, breast cancer patients who use therapeutic doses of vitamin D3 (4000 to 6000 IU a day) should have a regular blood chemistry panel that will reveal kidney toxicity and calcium imbalances while these problems are still reversible. The importance of melatonin and vitamin D3 will be discussed later in this protocol.

Flavonoids
Soy contains genistein that belongs to group of substances called flavonoids. Studies have demonstrated that genistein has certain anti-estrogenic properties and can inhibit the development of breast cancer cells. Soy can also inhibit the tendency for cancerous tissue to create new capillaries to supply it with blood. Indeed, substances that demonstrate anti-angiogenesis properties have recently been a hot topic in the war against cancer. The theory is, if you can prevent the tumor from developing new blood vessels, you can starve and ultimately kill it. Genistein has been demonstrated to affect the ability of cancer cells from sticking to one another. Cancer-cell adhesiveness is part of the process by which metastatic colonies of breast cancer cells form tumors in other parts of the body. Another study suggests that genistein may enhance the benefits of certain chemotherapeutic regimens.

There have been a number of studies conducted on genistein to determine its effect on the proliferation and maturation of breast cancer cells. In one, genistein inhibited growth but not maturation in both estrogen-positive and negative cell lines. This would suggest that the inhibition of cell growth is not dependent on genistein's inhibition of estrogen. Genistein was tested with a number of other naturally occurring flavonoids and was found to inhibit cell proliferation in estrogen-receptor-positive breast cancer cells. This inhibition was reversed when excess competing estrogen was added. Interestingly, the other flavonoids inhibited cell proliferation even when high levels of estrogen were added, suggesting that they work by a different mechanism than genistein. One of those flavonoids is quercetin. This suggests that taking supplemental quercetin might be useful in treating breast cancer. Quercetin is most effective in a water-soluble form. While it is difficult to find water-soluble quercetin in the United States, it is expected that this form will soon be available as a dietary supplement. Quercetin supplementation should be considered in treating and perhaps preventing breast cancer.

Another study was conducted in which both genistein and supplemental curcumin were tested to evaluate their ability to inhibit the growth of estrogen-receptor-positive breast cancer cells that were induced by pesticides. Pesticides and other petrochemicals have estrogenic effects; one of the theories regarding the increased incidence of breast cancer is the proliferation of these types of chemicals in our environment. The study demonstrated a synergistic effect resulting in the total inhibition of cancer cell growth. Though more studies are needed, curcumin should be considered in the treatment and prevention of breast cancer.

The most potent soy extract on the market is called Mega Soy Extract. It contains more than 40% pure soy isoflavones . . . much higher than previous soy products. The suggested dose for nonestrogen-receptor-positive breast cancer patients is five 700-mg capsules of Mega Soy Extract four times per day. This provides the optimal daily dose of approximately 2800 mg of standardized genistein. Genistein is rapidly metabolized within the body, which makes it necessary for cancer patients to take Mega Soy Extract in four divided doses spaced evenly throughout the day.

Caution: Breast cancer patients about to undergo radiation therapy should stop using soy products 1 week before, during, and after being treated. The therapeutic effects of radiation therapy are dependent upon the activity of an enzyme called protein kinase C. Soy inhibits this activity and therefore could theoretically undermine the radiation therapy. Women with any type of breast cancer should also test their serum estrogen levels to make sure that too much estrogen is not present if they are taking high doses of soy. Estrogen can combine with the genistein to cause some breast cancer cells to grow faster. Other studies show that genistein blocks certain types of estrogen-receptor sites, thus inhibiting the proliferation of these types of breast cancer cells.

Melatonin
An important supplement for the breast cancer patient is the hormone melatonin. High doses of the hormone should be taken at bedtime. Melatonin blocks estrogen receptors somewhat similarly to the drug tamoxifen without the long-term side effects of tamoxifen. Furthermore, when melatonin and tamoxifen are combined, synergistic benefits occur. Melatonin can be safely taken for an indefinite period of time. The suggested dose of melatonin for breast cancer patients is 3 to 50 mg at bedtime. Melatonin not only blocks estrogen-receptor sites on breast cancer cells, but directly inhibits breast cancer cell proliferation and boosts the production of immune components that kill metastasized cancer cells.

There have been some studies demonstrating changes in melatonin and other hormone levels in breast cancer patients. In one study, breast cancer patients demonstrated lower melatonin levels than women without breast cancer. Normally, we undergo a seasonal variation in the production of certain hormones, including melatonin. A study comparing healthy women to women with a history of breast cancer demonstrated that the women with breast cancer did not have a seasonal variation in melatonin levels as did the healthy women. Of course this begs the question: Are these findings a contribution to the cause of breast cancer or a result of the disease?

Vitamins A, D, E and Selenium
Vitamin A and vitamin D3 inhibit breast cancer cell division and can induce cancer cells to differentiate into mature, noncancer cells. Vitamin D3 works synergistically with tamoxifen (and melatonin) to inhibit breast cancer cell proliferation. Breast cancer patients should take 4000 to 6000 IU of vitamin D3 every day on an empty stomach. Water-soluble vitamin A can be taken in doses of 100,000 to 300,000 IU every day. Monthly blood tests are needed to make sure toxicity does not occur in response to these relatively high daily doses of vitamin A and vitamin D3. After six months, the doses of vitamin D3 and vitamin A can be reduced.

Vitamin E and vitamin E succinate inhibit tumor cell growth in vitro and in vivo. In a recently published study, vitamin E succinate, a derivative of fat-soluble vitamin E, inhibited growth and induced apoptotic cell death in estrogen-receptor-negative human breast cancer cell lines. The study concluded that vitamin E succinate may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are resistant to anti-estrogen therapy. All breast cancer patients should consider taking 1200 IU of vitamin E succinate per day. Selenium has been shown to directly induce growth arrest and cell death in breast cancer cells of mice. Although no human studies have been done, it is suggested that patients with breast cancer take 200 micrograms (mg) of organic selenium (selenomethionine), two to three times per day.

Caution: When taking doses of vitamin D3 in excess of 1100 IU per day, regular blood chemistry tests should be performed in order to monitor kidney function and serum calcium metabolism. Those with thyroid cancer should avoid vitamin A.

DHEA and Pregnenolone
Dehydroepiandrosterone (DHEA) and pregnenolone may be thought of as steroid precursors whose exact function is unclear. They are both present in the body at any given time and are part of the synthetic pathway of many of the adrenal steroids. At the present time existing studies make it unclear as to whether or not these hormones should be taken by breast cancer patients. Some studies have demonstrated a positive impact while others a negative one. From the standpoint of preventing breast cancer, the preponderance of scientific literature indicates that maintaining youthful levels of DHEA is beneficial. The Life Extension Foundation, however, cannot support the use of pregnenolone or DHEA by breast cancer patients at this time, and recommends that they not be used.

CoQ10
CoQ10 (coenzyme Q10) has demonstrated promise in treating breast cancer. Although there are only a few studies, the safe nature of CoQ10-coupled with promising research-suggests that breast cancer patients should take 100 mg three to four times per day.

Green tea
The most current research shows that some of the ingredients in green tea may have a beneficial effect in treating cancer. While drinking green tea is a well-documented method of preventing cancer, it is difficult for the cancer patient to obtain a sufficient quantity of anti-cancer components in that form. We suggest that a person with breast cancer take four to ten green tea extract capsules every day. Use capsules that contain a potent standardized extract of epigallocatechin gallate, the component of green tea that makes it an effective adjunct therapy in the treatment of breast cancer.

A novel herbal preparation
The September 17, 1998 issue of the New England Journal of Medicine published a study on a product called PC Spes that was 100% effective in reducing PSA levels in advanced prostate cancer patients. The company that makes PC Spes to treat prostate cancer also makes an herbal preparation called Spes to treat certain kinds of cancer including breast cancer. The Spes preparation has been shown effective in the two years that Foundation members have been using it. The studies show that Spes works best against cancers with a mutated p53 oncogene and an over-expressed N-RAS gene. Cancer patients have obtained positive results when combining Spes with high-dose genistein soy extract, curcumin and 83% green tea extract. What follows is a highly technical description of the molecular mechanisms of action of Spes. Please do not be intimidated if you are unable to fully understand the description... it is written to inform the oncologist as well as the lay person.

Spes has been shown to inhibit prostaglandin E2 (PGE2) by about 50%. Cancer patients often develop high concentrations of PGE2 that can promote the proliferation of some cancer cell lines and also damage immune function. PGE2 inhibits the T-cell response, causes a decrease in natural killer (NK) cells, and inhibits lymphokine production. PGE2 enhances tumor survival by blocking the natural destruction via the lysis process of tumor cells. In addition, PGE2 promotes abnormal platelet aggregation, a common feature that enables cancer cells to enter the interstitial tissue through a blood vessel wall to establish metastatic sites. PGE2-induced endothelial cell damage attracts metastatic cancer cell colony formation. Many cancer patients succumb to acute death when an abnormal blood clot (thrombus) causes a heart attack or stroke. It is clearly desirable to suppress PGE2, and Spes does this by about 50%. The suppression of PGE2 by Spes has shown a dramatic increase in NK activity. While cancer drugs are in development that work by suppressing PGE2 formation, Spes is available as a dietary supplement for use today.

Nearly all cancer cells secrete a peptide hormone called substance P that promotes tumor growth. Substance P also functions as a neurotransmitter involved in pain pulse transmission through the nerves. Spes appears to lower the levels of Substance P, thus potentially slowing tumor growth and alleviating pain.

Spes increases enkephalin production. Enkephalins are peptides produced in the brain that act as opiates, binding to receptor sites involved in pain perception. This could be a mechanism by which Spes alleviates pain. Spes may increase enkephalins between 30% to 50% in about 1 hour.

Beta-Endorphin levels are markedly depressed in the cerebrospinal fluid of cancer patients. Endorphins are polypeptides produced in the brain that also act as opiates producing an analgesic effect by binding to opiate receptor sites. The most active of the endorphins is beta-endorphin; Spes has been shown to normalizes beta-endorphin levels. Another mechanism by which Spes provides analgesic action is by lowering norepinephrine in relation to serotonin. Spes raises acetylcholine levels in the brain by an average of 60.4%. This also has a positive effect on pain reduction.

Spes increases cAMP (adenosine 3',5'-cyclic monophosphate) by a dramatic 150%, but has only a modest effect on cGMP (cyclic guanosine monophosphate). This induces a hyperpolarization of the postsynaptic membranes, causing an inhibition of the pain signal transmission, but not a blockage of the opium receptors. High levels of cAMP also normalize mitosis, i.e. cell division. Thus, Spes may promote cell differentiation and inhibit abnormal cell growth via its effects on cAMP and cGMP.

Spes reduces the afferent peripheral pain signals and increases the central pain-modulating function. This is a fancy way of saying Spes causes a reduction in internal organ pain or bone pain.

In the animal model, Spes was directly injected into the tumor site and caused an inhibition rate of 133% in tumor weight or volume. On hepatocarcinoma cell lines, Spes markedly reduced the number of survived cells in a total unit area, reversed the self-keeping system of the cancer cells, and caused the differentiation of the cancer cells to normal cells. By causing the cancer cells to differentiate normally, Spes may markedly inhibit the advancement of the tumor.

Alpha-Fetoprotein (AFP) is a specific marker for gene expression in hepatocellular carcinoma. AFP is a serum protein produced by the fetal liver and yolk sac during prenatal development and reaches its full expression at 15 weeks of gestation, falling rapidly thereafter until normal adult levels are reached. High levels in an adult is an indication of hepatocellular carcinoma. Spes was shown to block expression of AFP by 83.5%.

N-RAS gene is a "transforming" gene whose over-expression is required for the activation of hepatocellular carcinoma and approximately 30% of all other cancers. A mutation in the N-RAS gene tends to turn off the switch that regulates cell proliferation. N-RAS thus interacts with other proteins and simulates cell growth. Spes was shown to block the over-expression of N-RAS gene.

Ribosomal RNA instructs specific ribosomes to join into a group called ribosomal complex. This is the production facility for making protein. A ribosome is a cell organelle. It is the site of amino acid assembly in the exact sequence ordered by messenger RNA (mRNA). mRNA receives instructions (the genetic code) in the nucleus for the exact sequence of the 22 different amino acids necessary to make a specific protein. This process is called transcription. It is at this point that over-expression often occurs, where the cell turns cancerous. IGF-II has a growth promoting effect on cells and Spes blocks the over-expression of mRNA for IGF-II synthesis.

Finally, Spes increases SOD production in the blood serum by 50% and suppresses free radical generation.

Dosage recommendations are based on body weight. Under 150 lbs.: two capsules two hours before breakfast on an empty stomach, and again two capsules two hours prior to dinner on an empty stomach. Over 150 lbs. of body weight: three capsules two hours before breakfast on an empty stomach, and again three capsules two hours prior to dinner on an empty stomach. An empty stomach means no food or any other medication or supplement during the two-hour period. Spes requires a noncompetitive stomach environment for proper absorption.

The pain relieving effect should be felt within two hours. Also, mood and appetite should improve as well. Botaniclab, the product's manufacturer, claims that Spes works as well as hydrazine sulfate in countering the cachexia that occurs in late-stage cancer. Testing for blood tumor markers and tumor volume should be regularly conducted to determine whether Spes is effective against the individual's cancer.

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