|Alternative Medicine in Breast Cancer|
BRIEF CLINICAL UPDATE
Alternative Medicine in Breast Cancer
Anh Kieu, M.D.
Alternative medicines interventions are not widely taught or used in medical schools and U.S. hospitals. Definitions of alternative medicine vary but can include relaxation, massage, megavitamins, spiritual healing, folk remedies, herbal medicines, chiropractic, lifestyle and commercial diets, energy healing, homeopathy, hypnosis, biofeedback, and self-prayer. Surveys suggest 10-50% of the world wide population use alternative medicines at an estimated cost of $21-$33 billion in 1997. Approximately 65% of the patients paid for treatment themselves without insurance coverage. There has been a 380% increase of herbal medicine use and 130% increase of high dose vitamins use, reflecting increasing availability in stores.1
Up to 50% of cancer patients use complementary and alternative medicines. Surveys found the majority of users do not tell their physicians and have concurrent conventional treatments. Approximately 10% of cancer patients use alternative medicines instead of mainstream medicine. Examples include laetrile, metabolic diets, shark cartilage, high-dose vitamins, and electromagnetics.2 Studies have found that breast cancer patients were more likely to use alternative therapies in conjunction with conventional treat-ments.3 Newly diagnosed early-stage breast cancer patients on standard therapies who reported depression, fear of recurrence, more physical symptoms, and lower scores for mental health were more likely to use alternative medicines. Therefore the use of complementary and alternative medicine could represent a marker for potential psychosocial distress.4
In 1992, the NIH established the Office of Alternative Medicine to study unconventional medical practices. In 1998, it was renamed as the National Center for Complementary and Alternative Medicine and now supports ten research centers.2
Diet and Nutrition Cures
The theory supporting certain diets reducing cancer risk has been expanded to include cancer cures. Macrobiotic diets are popular and focus on the interplay of food, lifestyle, environment, and the individual to create health/disease. Orthomolecular medicine focuses on high dose vitamins and selected nutrients to aid the body's immune system. Linus Pauling popularized the consumption of high-dose vitamin C. However, studies did not show any superiority of vitamin C consumption to placebo.
Individual practitioners develop metabolic therapies. These treatments are combinations of diet, vitamins, minerals, enzymes, and detoxification regimens that aim to correct physiological imbalances. For example, the Gerson regimen consists of hourly consumption of crushed fruits and vegetables, and coffee enemas are used to remove dead cells and toxins. Patients also receive nutritional supplements. Detoxification regimens are also available in health food stores and books. These regimens utilize laxatives that can be dangerous when taken regularly.5
Mind-body techniques focus on using the mind to heal the body. An example is Bernie Siegel's Exceptional Cancer Patients Program, which combines meditation, visualization, therapy, support groups, and other exercises. Studies show no difference in length of survival of breast cancer patients who utilize mind-body techniques. However, some physicians accept their use because they improve the patient's psyche.2
Biologic treatments are invasive and utilize biologically active compounds. The best known is antineoplastons (peptides) developed by Stanislaw Burzynski. Antineoplastons were purported to slow or reverse tumor growth. The National Cancer Institute and Burzynski were to start clinical trials but failed to agree on a protocol and patient selection criteria. Other research at the Burzynski Research Institute raised criticisms that the treatments were toxic and useless.5
Shark cartilage gained interest as an antiangiogenic compound after the book "Sharks Don't Get Cancer" was published, but a recent phase I-II trial showed no benefit. Shark cartilage protein was deemed too large to be absorbed and are excreted.6,7
Traditional Chinese medicine includes herbal remedies and acupuncture/acupressure. Acupuncture/ acupressure is based on the principle that energy courses through the body and disease causes blockage that can be unblocked by healers.2 Acupuncture has been used as an adjunct in the treatment of postoperative and chemotherapy nausea and vomiting. Studies of acupuncture in pain management have shown pain relief and narcotics use reduced as well as effects on regeneration of nerve tissue in patients with peripheral neuropathy.8
Traditional Chinese herbal therapies have been purported to augment the immune function, ameliorate the effects of chemotherapy, and prevent cancer. Herbal agents have been reported to increase the CD4/CD8 ratio and T cell count. They also have effects on cytokine levels. However studies have been inadequate in terms of design and size to document clinical efficacy and further trials are needed. Herbs in the role of supportive therapy can help to restore peripheral blood counts and ease nausea and vomiting. In China, long-term prospective trials with herbs and cancer prevention showed some benefit in patients with cirrhosis with fewer cases of hepatocellular carcinoma. Also, patients with epithelial dysplasia had a lower rate of esophageal cancer in the treatment group versus the untreated control group. One study conducted in Beijing with 184 breast cancer patients reported results of 88.8% 5-year survival in patients taking an herbal remedy.8
There is concern that herbal medicines may have adverse effects on cancer treatments. Some herbs can photosensitize the skin to radiation, and some cause blood pressure swings. Others have anticoagulant effects and need to be discontinued prior to surgery.2
In 1993, the Canadian Breast Cancer Research Institute established the Task Force on Alternative Therapies and researched six popular treatments used by Canadian cancer patients.
Essiac is an herbal mixture widely used in Canada for 70 years. Essiac was developed by Rene Caisse, a nurse who obtained the recipe from a woman who said it cured her breast cancer. Ingredients include burdock root, Indian rhubarb, sheep sorrel, and the inner bark of slippery elm. It is reported to boost the immune system, increase appetite, reduce pain, improve quality of life, reduce tumor size, and increase survival. Essiac is now marketed as an herbal tea to reduce nausea, vomiting, and diarrhea. Ingredients have been studied and seem to help with quality of life but no clinical benefits of improved survival or tumor regression have been shown. Of note, it contains high levels of anthraquinone (adriamycin is an anthraquinone derivative).9
Green tea has been used in China and Japan for 5000 years as a stimulant and a digestive remedy. It has 10-80 mg of caffeine thus its use should be limited to 2 cups/day in pregnant and nursing women and cardiac patients. Epidemiological studies on green tea and cancer prevention suggested regular consumption might moderately reduce cancer risk, especially cancer of the upper digestive tract. In terms of cancer treatment, a few animal studies showed decreased tumor growth and reduced incidence of skin cancer development in animals exposed to skin carcinogens. Decreased metastatic potential and suppression of chromosomal mutations induced by carcinogens were also observed. However, the mechanism of action is not fully understood, and further research is necessary.10
Iscador is an extract of European mistletoe. Mistletoe is used in anthroposophic medical clinics in Switzerland and Germany. It is legally prescribed in South Africa and several European countries. Anthroposophy is the philosophy that blends science and spiritual principles and applies them to cancer treatment. Mistletoe is thought to have controlling properties that are deficient in cancer. It is reported to reduce tumor size, stimulate the immune system, and revert cells to more differentiated forms. Mistletoe is used in cervical, ovarian, breast, gastric, colon, and lung cancer to improve quality of life and survival. Laboratory studies showed increased DNA stability, decreased cell growth, and, in animal models, increased immune function. Clinical studies in Europe have shown improvements in quality of life, survival, and immune function. However, these studies had design limitations, and more research is necessary. Iscador is injected into the abdominal wall subcutaneously near the tumor site, and side effects include local inflammation at injection site.11
Oncologist Dr. Joseph Gold studied substances that can block gluconeogenesis since cancer cells get energy from anaerobic metabolism. He found hydrazine sulfate to be most effective and used it initially in breast cancer, sarcoma, Hodgkin, and other lymphomas. Gold advocated using hydrazine sulfate in conjunction with conventional therapies to get an enhanced effect. Hydrazine sulfate can normalize metabolism in cancer patients with cachexia. Clinical studies in Russia reported improvement in well-being, tumor stabilization, and survival. Results of U.S. studies showed zero to minimal effects. Side effects include nausea, pruritus, peripheral neuropathy, and drowsiness. Hydrazine, the metabolite of hydrazine sulfate, is liver toxic.12
Diets high in vitamins A, C and E may reduce the risk of some cancers but the specific agent for the protective effect is unknown. Therefore, nutritionists recommend fresh foods including fruits and vegetables instead of diet supplements. However many people take daily vitamin supplements. Cancer patients usually take daily doses greatly exceeding recommended daily intake. Proponents of mega dose vitamins based their recommendations on lab studies showing tumor suppression, positive immune function effect, and induction of cell differentiation.
Vitamin A's precursor is beta-carotene. Vitamin A and beta-carotene are proposed as chemoprophylactic agents for cancer based on epidemiological studies that showed higher cancer risk in populations with low dietary intake and low serum levels. Lab studies showed that retinoids enhance immune response, slow tumor growth, and decrease tumor size. In breast cancer, retinoids attach to receptors on breast cancer cells and influence gene expression and cell proliferation. Beta-carotene can increase production and tumoricidal activity of human monocytes, lymphocytes, and macrophages. Retinoids with interferons inhibit proliferation of malignant cells. Pre-clinical study with vitamin A analog (fenretinide) showed that it may be beneficial in the prevention and treatment of breast cancer. It has cytostatic activity in human cancer cell lines and inhibitory effect in rat studies. There is possible synergism between fenretinide and tamoxifen.
Clinical studies showed that retinol levels are lower in cancer patients versus controls. Plasma level increases with supplementation but the therapeutic effects are unclear. 13-cis-retinoic acid with inter-feron-alpha had positive effects in cervical cancer. Other retinoids and interferon are useful in cutaneous malignancies. However, there was an increased risk of lung cancer in smokers receiving beta-carotene and vitamin A. Vitamin A can cause headaches, irritability, peri-oral dermatitis, desquamation, and mega doses can cause liver damage. Beta-carotene is less toxic.13
Vitamin C is known to have effects on immune function, and it is believed that the body requires more vitamin C during physical or chemical stress. Epidemiological studies showed reduced risk of some cancers in populations with high vitamin C intake. This may be due to vitamin C's antioxidant effect or its ability to block N-nitrosamines formed in the stomach after ingestion of certain foods. There is a close association between high vitamin C levels and reduced risk of stomach cancer. In animal studies, tumor regression, tumor growth inhibition, and increased survival have been noted. However, two randomized studies in patients with advanced cancer had negative results.
Mega dose vitamin C can cause stomach irritation, headache, rash, and increased oxalate deposition in bladder/kidneys. Vitamin C can interfere with medications including anticoagulants, iron, vitamin B12, and vitamin E. High doses in pregnancy can lead to vitamin C deficiency in the newborn.13
Vitamin E is a fat-soluble vitamin that is found in many foods. The most common form in the Western diet is alpha-tocopherol. Low serum levels are associated with slightly increased cancer risk but the data are limited and inconsistent. The mechanism of action is poorly understood, but cancer prevention and treatment may be related to lipid antioxidant properties. Lab study with human breast cancer cell lines showed that vitamin E inhibited cell proliferation. Studies with benign breast disease and vitamin E supplements showed no benefit.
There are no in vivo or clinical studies.
There are no serious side effects with vitamin E supplementation in most adults but high levels can affect absorption of vitamins A and K. It should be used with caution in patients on anticoagulant therapy or those with vitamin K-related clotting disorders.13
Patients have been advised to take the Hoffer regimen, a combination of vitamins A, C, and E and selenium. Some studies have reported benefits with combination therapy but results are questioned due to weakness in the study methodology.13
Canadian scientist Gaston Naessens examined blood from healthy and cancer patients and saw "somatids" in cancer patients. He described two life cycles: microcycle (seen in healthy individuals) and macrocycle (seen in cancer). He theorized that environmental factor initiates macrocycle, and the somatids start to secrete toxic substances that interfering with immune cells and allow proliferation of primitive cells. These cells deplete the rest of the body of nitrogen and, he developed 714-X to interfere with somatidian macro-cycle. The base is a camphor compound with added nitrogen to satisfy nitrogen requirement of cancer cells thereby freeing the body's nitrogen for immune cells. It is injected into lymph nodes in the groin.
A few studies with animals have shown no beneficial effect of 714-X. Cancer and AIDS patients have reported increased survival and quality of life. It is increasingly being used in breast and prostate cancer patients. Camphor has been shown to improve immune function, promote enzymatic breakdown of carcinogens, and increase susceptibility of cancer cells to radiation. However, camphor can have toxic effects when ingested.14
Jacobson et al reviewed the literature from 19801997 on clinical research with breast cancer patients and complementary and alternative medicine. They looked at studies designed to show 1) alteration of disease progression, 2) alleviation of symptoms of breast cancer, 3) relief of treatment side effects, and 4) improvement of immune function. They found 51 citations fitting their criteria. Modalities include 1) diet, nutrition, and lifestyle changes, 2) herbal medicine: iscador and other concoctions, 3) mind/body control: support groups, psychotherapy, and hypnosis, 4) pharmacologic/biologic treatment: antineoplaston, melatonin, laetrile, and hydrazine sulfate, and 5) energy therapy. There were no data about essiac, 714-X, macrobiotic diets, or shark cartilage. Two studies showed positive effects of melatonin on metastatic cancer (< 25% lesion increase and increased complete/partial response). Another study found that melatonin potentiates tamoxifen.15
Patients turn to complementary and alternative medicine to relieve side effects of cancer treatments. These include acupuncture for nausea/vomiting, massage for reduction of lymphedema, and mind/body techniques to reduce pain/stress. Despite anecdotal reports that show benefit with these alternative treatments, clinical studies have yet to provide clear answers. Though few alternative treatments have been shown to have definitive therapeutic effects on breast cancer, physicians should be aware of their use to facilitate open discussion with patients who choose to utilize these treatments.