Preventing breast cancer cell metastasis
Breast cancer cells frequently metastasize to the bone where they cause severe degradation of bone tissue.

The bisphosphonates are a class of drugs that protect against the degradation of bone, primarily by inhibiting excess activity of osteoclasts. The osteoclasts are bone cells that absorb and remove bone tissue so that the osteoblasts can bring together the minerals calcium, magnesium, and phosphorus to form new healthy bone. When osteoclasts become overactive, they break down too much bone and may result in a pathological reduction of bone density.

Among the known inhibitors of osteoclast activity, the bisphosphonates are the most promising drugs. Clodronate, one of the most investigated bisphosphonates, has been clinically utilized for over 15 years in treating malignant diseases. It is the most used, most effective, and safest drug in the treatment of hypercalcemia (too much calcium in the blood). It inhibits bone destruction, prevents bone fractures, relieves bone pain, and prevents the development of new bone lesions. Clodronate may even reduce mortality. Bisphosphonates such as clodronate are potent osteoclast inhibitors that have opened the way for a nontoxic medical treatment of bone metastasis.

Large-scale studies in humans with breast cancer indicate the benefits of prolonged administration of clodronate to reduce the frequency of pathological skeletal events and also the need for radiation therapy.

A New England Journal of Medicine study (Aug. 6, 1998) confirmed many previous studies showing that breast cancer patients receiving clodronate experienced about half the number of metastatic lesions to the bone compared to the placebo group. What was remarkable about the New England Journal of Medicine study was that it showed that clodronate also prevented metastasis to the visceral organs and that it significantly improved patient survival over a 36-month time period.

Another study showing improved survival was conducted in Finland, where breast cancer patients were treated with clodronate or placebo. Bone pain, extension of bone metastasis, and formation of new bony metastatic lesions were reduced by clodronate, and development of severe hypercalcemia was prevented during the first 12-month period. The patients were then withdrawn from clodronate treatment and were followed up for at least 12 months. There were fewer fractures and less hypercalcemia (too much calcium in the blood) in the patients previously treated with clodronate than in the placebo group. The survival rate was higher in the clodronate group compared to the placebo group. No side effects were observed in either group. While clodronate has been investigated as a therapy for advanced metastatic bone cancer in dozens of human studies, only two studies show that clodronate improved breast cancer patient survival. It would appear that if clodronate were administered earlier in the disease state, that it could significantly prolong survival, as was demonstrated in the New England Journal of Medicine study.

Since 1980, the Europeans have been studying the effects of clodronate in the management of hypercalcemia, bone pain, and skeletal complications in patients with bone metastasis. Controlled studies show that bone metastasis can be prevented or delayed in patients receiving clodronate. The bisphosphonate drug clodronate is now the standard therapy (after hydration) that German doctors use to treat malignant states of hypercalcemia.

As was previously stated, tumor-induced hypercalcemia is essentially due to an increase in osteoclast-induced breakdown of the bone into the blood. During this process of bone destruction, substances such as growth factors are released that promote tumor cell growth. Since the bisphosphonates are potent inhibitors of osteoclast activity, they represent an effective method of safely treating hypercalcemic event that frequently occurs in patients with breast cancer and other diseases.

In a double blind multicenter study, the effect of intravenous clodronate plus hydration was compared with placebo plus hydration in the treatment of hypercalcemia in breast cancer patients with bone metastases. A significant difference in favor of clodronate was observed in the time to reach normal blood calcium. A total of 17 patients of 21 patients on clodronate achieved normal blood levels of calcium compared with only 4 of 19 patients on placebo. The only adverse event associated with clodronate was symptomatic hypocalcemia (too little calcium in the bone) in one patient.

The reason hypocalcemia is such a rare event is that patients having a positive response to clodronate normally show an increase in the calcium-regulating hormones such as parathyroid hormone. This homeostatic response probably explains why hypocalcemia occurs rarely in clodronate-treated patients. In 1991, Italian scientists reviewed 126 publications on clinical studies concerning the use of clodronate in the therapy of bone disease. These studies evaluated a total of 1930 patients in order to ascertain the effects following the short- and long-term administration of clodronate. The results of the large number of studies indicate that clodronate therapy does not have any clinically significant side effects and confirm its tolerability and safety. It is still, however, advisable to have a blood test within 10 days of initiating clodronate therapy, just to make sure that clodronate is not removing too much calcium from the blood.

Bisphosphonate drugs such as clodronate exert their analgesic effect by several mechanisms. The long-term effects are probably due to osteoclast inhibition. The acute pain-relieving effect, which occurs within days or a week, is likely to be associated with the reduction of various potentially pain-producing substances. In a controlled trial using clodronate in patients with metastatic bone disease and pain, 57% of patients in pain chose clodronate, while 26% chose placebo, and eight (17%) had no preference. For the investigators who also made a blinded selection, clodronate was chosen in 65% of patients compared to placebo in 22% patients, and no difference was apparent in 13%.

In an observational study involving 398 tumor patients with bone metastases or related hypercalcemia, the effect of treatment with clodronate over a period of 12 months was investigated. Bone pain, analgesic requirements, quality of life, and laboratory parameters were recorded at monthly intervals. The results showed that some 71.4% of all patients indicated an improvement in quality of life. In another study, 20 postmenopausal women (aged between 46 and 67 years old) with skeletal metastases from breast cancer were treated with clodronate for 15 days. All patients received standard hormonal therapy (tamoxifen). These results showed that clodronate provided pain relief in 75% of treated patients and serum bone marker levels indicated stabilization of skeletal metastatic lesions. In a randomized, double-blind, placebo-controlled trial of oral clodronate, 173 breast cancer patients with bone metastasis were treated with clodronate or an identical placebo. In patients who received clodronate, there was a 47% reduction in the number of episodes of hypercalcemia, a 32% reduction in the incidence of vertebral fractures, and a 43% reduction in the rate of vertebral deformity. Trends were seen in favor of clodronate for nonvertebral fracture rates and bone pain. In patients who receive clodronate before developing bone metastasis, the results are more dramatic, showing consistent 50% reductions in skeletal metastasis and fractures. An inevitable conclusion may be that all breast cancer patients should consider supplementing with an 800-mg clodronate supplement, twice a day for prophylactic purposes.

Women with primary breast cancer who receive chemotherapy may experience ovarian failure or early menopause, leading to a loss of bone mineral density. A double-blind trial was conducted to evaluate women with breast cancer who were given clodronate or placebo for two years. Those who received oral clodronate showed reduced bone density loss compared to placebo. All of the patients in the trial received conventional treatment for breast cancer. In another study, the effect of clodronate on bone mineral density was studied in 121 postmenopausal breast cancer women without skeletal metastases. At two years, clodronate combined with the anti-estrogen drugs tamoxifen or toremifene markedly increased bone mineral density in the lumbar spine and femoral neck by 2.9 and 3.7%. There were no significant changes in the patients given anti-estrogen drugs only. Doctors often advise cancer patients using clodronate to take plenty of calcium, magnesium, and even phosphorus to enable the bone to regenerate.

The molecular mechanisms by which tumor cells degrade bone involve tumor cell adhesion to bone as well as the release of toxic chemicals from tumor cells that stimulate osteoclast-induced bone degradation. Bisphosphonates inhibit cancer cell adhesion to the bone matrix and inhibit osteoclast activity. By preventing tumor cell adhesion, bisphosphonates are useful agents for the prophylactic treatment of patients with cancer that is known to preferentially metastasize to bone.

There is evidence that growth factors such as insulin-like growth factor and transforming growth factor are released when the bone matrix is degraded. These growth factors could stimulate tumor cell proliferation throughout the body, which may be a reason that early use of clodronate significantly improved survival.

In a study to determine the effects of clodronate in women with advanced breast cancer, 133 patients with recurrent breast cancer, but no evidence of skeletal metastases, were randomly allocated to receive clodronate by mouth or an identical placebo for three years under double-blind conditions at two clinical oncology centers in the UK and Canada. The number of skeletal metastases was significantly lower with clodronate treatment than with placebo. The complications of skeletal disease were fewer by 26% in clodronate-treated patients compared to controls. Compared to placebo, significant effects in favor of clodronate were observed for vertebral deformities and nonvertebral fractures. The doctors concluded that oral clodronate significantly decreases the number and complications of skeletal metastasis in women with advanced breast cancer.

The reported studies of clodronate in the management of bone metastasis suggest a significant palliative role for this drug in those with advanced disease. An analysis of the hospital costs associated with the management of metastatic disease suggested that there are significant savings to be gained from the use of clodronate if only a 20% reduction occurs in the incidence of fractures, hypercalcemia, and hospital-based treatment for pain control (via radiation therapy).

Of the many compounds belonging to the bisphosphonate family, clodronate has been the most widely used in treating hypercalcemia and metastatic malignancy to the bone. All published reports indicate that clodronate can normalize plasma calcium in the majority of cancer patients. A large number of clinical studies indicate that clodronate is a safe and efficacious drug.

Some Published Studies on Clodronate
"Breast cancer patients with multiple bone metastasis were treated with clodronate (1600 mg/day) or placebo for 12 months. After withdrawal of treatment, the patients were followed up for at least 12 months. There were less fractures and less hypercalcemia in the clodronate group than in the placebo group. The survival rate was higher in the clodronate group than in the placebo group. No side-effects were observed in the clodronate group." Biomed Pharmacother (France) , 1988, 42/2 (111-116)

"The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations with clodronate was evaluated in 28 patients with various types of malignant tumors. Oral clodronate successfully reduced a mean serum calcium concentration in 22 out of 25 patients after 3-12 days (800-3200 mg/day). It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia." Acta Med Scand (Sweden), 1987, 221/5 (489-494)

"We investigated the acute effect of hydration plus intravenously administered clodronate. By the third day of observation, the clodronate produced a significant reduction in serum calcium levels compared to the placebo patients who received hydration only. There were no toxicities observed. Intravenously administered clodronate appears to be an excellent agent for the acute treatment of malignancy- associated hypercalcemia." Arch Intern Med (USA), 1987, 147/5 (937-939)

"We have assessed the effects of clodronate daily by mouth for up to 3 months in 17 episodes of hypercalcemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcemia and osteolysis in patients with carcinoma." Br J Cancer (England), 1985, 51/5 (665-669)

"Clodronate is very effective against osteoclasts. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were randomized to a clodronate or placebo regimen. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease." Presse Med (France), 1984, 13/8 (479-482); (also published in the New England Journal of Medicine, 1983, 308/25 (1499-1501))

"Clodronate and etidronate were injected in various doses in 6 patients with one or multiple episodes of malignant hypercalcemia. All patients responded well to the drugs after a delay period of 2 to 7 days. The tolerance of the drugs was excellent. Etidronate and especially clodronate, are promising agents for treating hypercalcemia and inhibiting bone resorption in malignant disorders." Cancer (Philadelphia), 1981, 48/8 (1922-1925)

"30 patients with disorders of calcium metabolism were treated with clodronate by mouth (1.6 g/day). Serum-alkaline-phosphatase and urinary hydroxyproline fell to normal or near-normal within 3-7 months, and there was a clinical improvement in all but 1 patient. Clodronate also reduced plasma-calcium and urinary calcium in 17 patients with hypercalcemia due to primary hyperparathyroidism or secondary to malignant disease. Clodronate seems to be an effective oral drug for inhibiting excessive bone resorption in man." Douglas, D.L., Duckworth, T., Russell R.G. et al., Dept. Hum. Metab., Univ. Sheffield Med. Sch., Sheffield UK Lancet (ENGLAND), 1980, 1/8177 (1043-1047)

Clodronate
Clodronate is not approved in the United States, but the FDA did approve some expensive bisphosphonate drugs a few years ago. These drugs may not work as well as clodronate and they produce side effects that could keep some breast cancer patients from using them for three to five continuous years. One FDA-approved bisphosphonate drug is called pamidronate and is sold under the trade name Aredia. The problem with Aredia is that it costs about $2,000 per month and must be administered in a medical setting via a four- to 24-hour intravenous infusion.

The high cost of Aredia has caused HMOs and other insurance companies to refuse to pay for it in early stage breast cancer. What's worse, many physicians are not even familiar with bisphosphonate drug therapy, and therefore won't prescribe it to their patients.

One reason insurance companies can avoid paying for Aredia in early stage breast cancer is that the FDA has approved it for the treatment of "moderate to severe hypercalcemia associated with malignancy." Women with metastatic breast cancer often do not manifest serious hypercalcemia until the disease has significantly progressed. The FDA has thus restricted the use of Aredia in a way that makes it more of a palliative therapy in advanced disease, rather than a potential life saving therapy.

Out of concern for toxicity, the FDA cautions against immediate retreatment with Aredia if the initial dose fails. Cancer patients are advised to undergo intravenous infusions of Aredia every three to four weeks. At $2,000 per infusion, few people can afford it.

Clodronate, on the other hand, is so safe that cancer patients can start taking two 800-mg capsules per day as soon as they are diagnosed. The fact that clodronate is nontoxic, is not terribly expensive, and has been shown to improve survival would make it the drug of choice in a free market.

Americans, however, are not free to make their own choices about medicines. The FDA does this for us.

A review of the published literature provides conflicting results as to whether clodronate or Aredia is the better drug. Proponents of Aredia state it provides a longer period of remission from hypercalcemia. One study compared single infusions of either Aredia or clodronate at the highest doses commonly used. A total of 100% of patients in the Aredia group achieved normal serum calcium following infusion of Aredia, compared to 80% receiving clodronate.

The median time to achieve normal serum calcium was a range of four days for Aredia and three days for clodronate. The median duration of normalized serum calcium was 28 days after Aredia and 14 days after clodronate. Two patients who failed to respond to clodronate were successfully treated with Aredia. Another two patients experienced fever after Aredia but no significant toxicity was observed with either treatment.

The doctors concluded by stating, "...both agents are effective in the management of hypercalcemia of malignancy. At the doses studied, the effects of Aredia are more complete and longer lasting than those of clodronate." What the above study did not mention is that clodronate can be taken orally every day, while Aredia administration is restricted to intravenous infusion. The fact that the calcium normalizing effects of a single dose of Aredia lasted twice as long as a single dose of clodronate does not reveal much, since it was already known that clodronate should be taken orally, on a daily basis, to maintain its effects.

The major unpleasant side effect to Aredia is a transient fever, sometimes accompanied by flu-like symptoms such as myalgia and lymphopenia. These effects, occur commonly after the first infusion of Aredia. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcemia, and rarely, ocular complications (uveitis and scleritis), and irritation at the site of infusion. Clodronate, on the other hand, appears to be free of unpleasant side effects other than the very rare case of it causing too little calcium in the blood (hypocalcemia).

There is no evidence to show that Aredia increases survival or prevents the development of metastasis in breast cancer, while there are two studies that show clodronate can improve survival. The greatest concern to cancer patients, however, may be that Aredia has been consistently shown to significantly elevate blood levels of the cytokines tumor necrosis factor (TNF) and Interleukin-6 (IL-6). Clodronate does not increase these cytokines. TNF and IL-6 have differing effects on various cancer cell lines.

One study to compare the effects of Aredia and clodronate on cancer patients showed a significant decrease in lymphocyte and leukocyte count in the Aredia group. In the same group, seven patients (24%) showed a transient increase of body temperature. These changes were not found in the patients treated with clodronate. Plasma IL-6 and TNF levels increased significantly after Aredia treatment, whereas no change was seen after clodronate infusion.

Breast cancer patients already have elevated levels of TNF and IL-6. Elevation of these two cytokines reflects an advanced disease state and impending death. TNF is also involved in inducing autoimmune inflammatory disease. A study evaluated the possible anti-inflammatory action of Aredia and clodronate and found that low concentrations of Aredia induced the IL-6 secretion while higher levels of Aredia were toxic. The induction of IL-6 or toxic effects were not observed with clodronate.

A study was undertaken to evaluate the relationship between serum TNF and cachexia (wasting syndrome) in patients with prostate cancer. Serum TNF activity was positive in 76% of the patients with relapsed disease, whereas only 11% of the untreated patients and 0% of the patients in remission as a result of endocrine therapy were positive. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower than the corresponding values in patients with undetectable serum TNF levels. There was a significant correlation between the detectability of serum TNF and performance status. Patients with elevated serum TNF levels had a significantly higher mortality rate than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to cachexia in patients with prostate cancer. This study clearly shows that prostate cancer patients do not want to elevate TNF. Aredia elevates serum TNF, clodronate does not. When it comes to prostate cancer, clodronate appears to be a lot safer.

A high serum level of IL-6 is regarded as a predictor of poor prognosis in multiple myeloma. A three-year study evaluated the effect of IL-6 on a large group of multiple myeloma patients. The patients with high levels of IL-6 were at very high risk of dying within three years from diagnosis. The doctors concluded that serum IL-6 is a significant marker of disease progression in multiple myeloma. A study on serum in human breast cancer patients revealed levels of serum IL-6 correlated with the stage of progression and with axillary lymph node involvement. The doctors concluded that high levels of IL-6 indicates more advanced disease. Aredia increases IL-6 levels, and is also used frequently by doctors in the U.S. to treat multiple myeloma. However, in the U.S., doctors cannot treat patients with clodronate, even though it does not boost toxic IL-6, because the FDA will not allow it to be sold to American citizens.

Angiogenesis (the formation of new blood vessels) is an essential requirement for tumor growth and metastasis. TNF is a factor known that promotes tumor angiogenesis in breast cancers. Scientists are looking at therapies to lower TNF as a way of inhibiting tumor angiogenesis. It would appear that most cancer patients would not want to increase their TNF level because the resulting formation of new blood vessels would enable their tumor to grow and develop metastatic colonies. Aredia causes TNF to elevate, whereas clodronate does not affect TNF levels.

Leptin is a hormone believed to regulate body weight. Doctors studied the effect of TNF infusion on serum leptin levels in six patients with solid tumors. TNF infusion on day one resulted in an increase in serum leptin levels from 3.1 to 5.2 . Similar results were obtained when TNF was infused on subsequent days. The study indicates that the increase in TNF- induced leptin may be a mechanism by which TNF induces cachexia in cancer patients. Another study investigated the correlation between the serum TNF levels and breast cancer severity. Forty consecutive patients with invasive breast cancer undergoing modified radical mastectomy were prospectively included and evaluated. High preoperative levels of TNF reflected a more advanced stage of invasive breast cancer. To reiterate, Aredia boosts TNF levels, but clodronate does not.

Many scientific studies indicate that IL-6 is associated with poor prognosis in breast cancer. One study indicated that elevated IL-6 in breast tumors may induce genetic change in tumor cells conferring a survival advantage by rendering them resistant to chemotherapy drugs.

Data from clinical trials indicate that clodronate is better tolerated, though the complication rate for Aredia is still very low.

Another expensive FDA-approved bisphosphonate drug is called Fosamax (alendronate). Fosamax can be taken orally, but is not indicated for the early treatment of breast cancer. Fosamax may produce side effects that will preclude its long-term use in certain women.

How to use Clodronate
Published studies indicate that clodronate administered intravenously or orally has the same long-term effect in most cases. Intravenous administration of drugs occurs frequently because people in other countries often do not take their prescription medicines. The standard dosage for treating cancer is 800 mg of clodronate, taken twice a day. In some studies, twice this dosage has been safely used. It should be noted that bisphosphonate drugs such as clodronate are considered adjuvant cancer therapies because conventional therapies are almost always used with clodronate. In other words, clodronate does not directly kill cancer cells, but it does prevent metastasis.

Breast cancer patients may want to consider a three- to five-year regimen of clodronate therapy. Blood tests to measure serum calcium levels and kidney function should be performed 10 days after initiating clodronate therapy, and then every one to two months thereafter. The concern for a small minority of people is that clodronate will cause too much calcium to be pulled from the blood. Regular blood testing will detect a serum calcium deficit.

Here is an actual example of a person who developed a serum calcium deficit:

"We present a patient with prostate cancer who developed symptomatic hypocalcemia while taking oral clodronate for painful bony metastases. He had a past history of a bowel resection for Crohn's disease and, although he was normocalcemic prior to taking clodronate, it is likely that the surgery had caused mild hyperparathyroidism. The addition of clodronate prevented the chronic osteolysis of bony metastases, which would have helped maintain normocalcemia. The case was complicated by hypomagnesemia and hypokalemia resulting from diarrhea. Hypomagnesemia is a cause of refractory hypocalcemia and hypokalemia. This case illustrates two important points. First, care must be taken with bisphosphonates in patients with a previous bowel resection. Second, magnesium plays a key role in the metabolism of both calcium and potassium, and must be considered in the evaluation of the hypocalcemic patient."

Other supplements
There are phytochemicals in cabbage and broccoli that interfere with breast cancer cell growth. Studies show that the phytochemical indole-3-carbinol changes the ratio of estrogen metabolites, in particular, reducing the amount of 16-alpha-hydroxyestrone which stimulates breast cells. The daily juicing of fresh organic cabbage and/or broccoli is suggested for breast cancer patients. For those who find it too inconvenient to juice cabbage and broccoli every day, there is a product called Phyto-Food powder that is composed of potent concentrations of broccoli, cabbage and other cruciferous vegetables that contain phytochemicals that help fight cancer. Breast cancer patients should take two heaping tablespoons of Phyto-Food powder every day. Indole-3-carbinol is also available from a compounding pharmacy as a capsule; 250 to 500 mg should be taken twice per day.

One of the most exciting new therapies in the prevention and treatment of breast cancer is conjugated linoleic acid (CLA). CLA is the component of beef that has direct breast cancer cell inhibitory effects. CLA has been shown both in vitro and in animal models to have strong anti-tumor activity. Particular effects were observed on the growth and metastatic spread of transplantable mammary tumors. One study examined the effect of dietary CLA on the growth of human breast adenocarcinoma cells in mice. Dietary CLA inhibited local tumor growth by 73% and 30% at nine and 14 weeks postinoculation, respectively. Moreover, CLA completely abrogated the spread of breast cancer cells to lungs, peripheral blood and bone marrow. This indicates the ability of dietary CLA to block the local growth and systemic spread of human breast cancer. For breast cancer prevention, six 500-mg capsules of CLA should be taken each day. For treatment, it is suggested that ten 500-mg capsules of CLA be taken daily. Estrogen-receptor negative breast cancer patients should take at least five 700-mg Mega-Soy Extract capsules per day to provide about 800 mg of genistein which may work synergistically with CLA.

Lignins are an important class of phytochemicals found in flax seed. When rats are fed a diet containing ground flax seed, it becomes very difficult to develop a breast tumor, even when breast cancer cells have been injected directly into the animal. Rats not given flax seed readily develop breast cancers in response to injections with live cancer cells. When rats with large breast tumors were fed flax seed, the breast tumors shrunk. In laboratory monkeys who eat lignins in their lab chow, it is very difficult to induce breast tumors. Ground flax seed (but not flax oil) provides a healthy dose of lignins. The most efficient way of consuming fresh flax seed with other cancer-fighting phytochemicals is to consume two to five tablespoons per day of The Missing Link for Humans, a specially designed flax seed-based meal replacement food.

Garlic is a well-established cancer-preventing nutrient. A study investigated aged garlic extract in an effort to determine whether it could inhibit proliferation of cancer cells. The proliferation and viability of erythroleukemia and hormone-responsive breast and prostate cancer cell lines were evaluated. The erythroleukemic cells were not significantly affected by the garlic extract, but the breast and prostate cancer cell lines were clearly susceptible to the growth-inhibitory influence of aged garlic extract. The anti-proliferative effect of aged garlic extract was limited to actively growing cells. This study provided evidence that garlic can exert a direct effect on established cancer cells.

Whey appears to inhibit the growth of breast cancer cells at low concentrations. One clinical study with cancer patients showed a regression in some patient's tumors when fed whey protein concentrate at 30 grams per day. Whey appears to deplete cancer cells of glutathione, thereby making them susceptible to conventional treatment with radiation or chemotherapy.

Prolactin
Breast cancer patients often have elevated levels of the pituitary hormone prolactin. Abnormally high levels of prolactin can interfere with successful breast cancer therapy. If a blood test reveals elevated prolactin levels, the oncologist should be encouraged to prescribe 1.25 to 2.5 mg of the drug Parlodel, also known as bromocriptine. Parlodel must be taken after meals because severe nausea can occur when it is taken on an empty stomach. A better way to suppress prolactin is with Dostinex. Twice a week dosing of 0.25 to 0.50 mg is all that is needed, and side effects are rare. Breast cancer patients should endeavor to keep their prolactin to under three nanograms per milliliter on a standard prolactin blood test, and Dostinex will accomplish this in most people.

Other treatments
The Life Extension Cancer Protocol lists other alternative cancer treatments that may help breast cancer. Call The Foundation for more information: 1-800-544-4440.

Laboratory testing
Breast cancer patients whose tumor cells have a mutant p53 oncogene are far more likely to benefit from soy extract supplementation. Only a pathology examination of the actual cancer cells can determine p53 status. An immunohistochemistry test can help to determine the p53 status of tumor cells. The following laboratory can perform this new test:

IMPATH Laboratories 1010 Third Avenue, Suite 203 New York, N.Y. 10021 Phone: 1-800-447-5816

IMPATH Laboratories measures the presence of mutant p53 oncogene. If the test is positive, you have mutant p53 and are more likely to benefit from soy extracts. If the test is negative, it indicates that you have functional p53 and are less likely to benefit from soy extracts. The Foundation realizes that many cancer patients seeking to use soy supplements may find it difficult to have an immunohistochemistry test performed to ascertain p53 status. Monthly blood testing for breast cancer patients is mandatory. Every patient responds differently to both conventional and alternative cancer therapies. The results of blood tests provide critically important data to evaluate the effectiveness of whatever therapies are being used. The blood tests commonly used by doctors to evaluate progression or regression of breast cancer are CA 27.29, CEA, prolactin, GGTP, and alkaline phosphatase. If, for instance, the CA 27.29 tumor marker were to continue to elevate 30 to 60 days after initiating soy extract supplementation, discontinue its use and seek another therapy immediately.

Monthly blood tests should include a complete blood chemistry with tests for liver function and serum calcium levels, prolactin levels, parathyroid hormone levels and the tumor marker CA 27.29 as well as cancer profile tests (CA Profile) that include the CEA and GGTP tests. These tests monitor the progress or failure of whatever therapies are being used, and also are able to detect toxicity from high doses of vitamin A and vitamin D3. The patient should insist on obtaining a copy of their blood work every month. Please refer to the Cancer Protocol for additional suggestions.

What about conventional therapies?
Surgery, radiation and cytotoxic chemotherapy are conventional treatments for breast cancer that have statistically increased survival rates in published studies. Despite the known toxicities of chemotherapy, it is difficult to argue against it since breast cancer cells have such an exceptional propensity to metastasize. The high failure rates associated with conventional breast cancer therapy has motivated most educated women to integrate alternative therapies into their treatment program. Few conventional oncologists, however, have sufficient knowledge of these alternative therapies and it is often up to the patient to stay fully informed.

Concluding Recommendations for Treatment of Breast Cancer

1. Mega Soy, five 700-mg capsule taken four times per day. Note cautions.
2. Vitamin D3, 4000 to 6000 IU taken daily on an empty stomach with monthly blood testing to monitor for toxicity. Reduce dosage at six months.
3. Water soluble Vitamin A, 100,000 to 300,000 IU taken daily with monthly blood testing to monitor for toxicity. Reduce dosage at six months. (Refer to Vitamin A precautions.)
4. Vitamin E succinate, 1200 IU taken daily.
5. Quercetin, 400 mg taken three times per day. (Water-soluble form will have a different dosage.)
6. Curcumin, 900 to 2700 mg taken per day.
7. Dostinex, 0.25 to 0.50 mg taken twice per week to suppress serum prolactin to under three nanograms per milliliter, if elevated.
8. Indole-3-carbinol, 250 to 500 mg taken twice per day.
9. CoQ10, 100 mg taken three to four times per day.
10. Green tea extract, four to 10 capsules containing at least 25% polyphenols taken daily.
11. Selenium (selenomethionine and selenate), 200 micrograms taken two to three times per day.
12. Conjugated linoleic acid, ten 50-mg capsules taken per day.
13. Flax - Udo's Choice, two to five tablespoons taken per day.
14. Garlic Caps, 800 mg taken five times per day.
15. Consider whey protein, 20 to 30 grams taken per day.
16. Consider Spes, two to three capsules, twice a day, two hours before meals. Individuals over 150 pounds should take three capsules and those under 150 pounds should take two capsules.
17. General guidelines for cancer treatment in the Cancer Protocol.
18. Consider conventional therapies.

Product availability: Melatonin, Phyto-Food, Mega Soy Extract, coenzyme Q10, green tea, Water-soluble vitamin A, vitamin D3 caps, conjugated linoleic acid, Udo's Choice, Whey, Garlic, Magnesium, Calcium, Pregnenolone, DHEA, Selenium, Vitamin E, and Curcumin.

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