Breast Cancer-7

Trastuzumab (Herceptin Genentech)
Trastuzumab (Herceptin Genentech) is an anticancer drug therapy for women with HER2-positive metastatic breast cancer. This monoclonal antibody therapy differs from traditional treatments, such as chemotherapy and hormone-blocking therapy. Herceptin works by specifically targeting tumor cells that overexpress the HER2 protein. A monoclonal antibody blocks the receptors and prevents activation of genes that induce cell division, thereby slowing the growth of the tumor.

The reported side effects are chills, diarrhea, nausea, weakness, headache, vomiting, and possibly damage of the heart muscle, anemia, and nerve pain. Trastuzumab can be used alone or in combination with the drug paclitaxel (Taxol) and is prescribed for metastatic breast cancer.


Paclitaxel (Taxol)
Paclitaxel (Taxol) belongs to the group of medicines called antineoplastics (anticancer drugs) that interfere with the growth of cancer cells and eventually destroy them. Because the growth of normal cells may also be affected by paclitaxel, side effects can occur. Some side effects may not occur until months or years after the medicine was used.

Side effects include neutropenia (decreased white blood cell count), anemia (decreased red blood cell count), thrombocytopenia (decreased platelet count), increased risk of infection, fatigue, bruising, hemorrhage, rash, itching, redness, hives, facial flushing, chest pain, difficulty breathing, high or low blood pressure, decreased heart rate, lightheadedness, dizziness, increased perspiration, shortness of breath, headache, numbness or tingling of the hands and/or feet, muscle aches, bone pain, mouth ulcers (sores), alopecia (loss or thinning of scalp and body hair), decreased appetite, diarrhea, nausea, vomiting, skin burns and ulcers, nail changes, hot flashes, and vaginal dryness.


Oophorectomy
Oophorectomy is surgery in which the ovaries are removed, therefore eliminating the body's main source of estrogen and progesterone in premenopausal women. Prior to the advent of anti-estrogen drugs, an oophorectomy was commonly used to treat breast cancer in premenopausal women.

Occasionally this procedure is still used in premenopausal women. However, chemotherapy drugs can alter the ovaries and reduce estrogen production. Tamoxifen may block any remaining estrogen effect on cancer cells, allowing many women to avoid surgery.


Natural Therapies

1)Protecting Against Dangerous Estrogens
2)Curcumin
3)Green Tea
4)Conjugated Linoleic Acid
5)Caffeine
6)Melatonin
7)Se-Methylselenocysteine
8)CoQ10
9)EPA and DHA
10)Vitamins A, D, and E
11)Tocotrienols

Protecting Breast Cells Against Dangerous Estrogens
I3C
How to Use I3C
The stronger form of estrogen, estradiol, can be converted into the weaker form, estriol, in the body without using drugs. Estriol is considered to be a more desirable form of estrogen. It is less active than estradiol, so when it occupies the estrogen receptor, it blocks estradiol's strong "growth" signals. Using a natural substance the conversion of estradiol to estriol increased by 50% in 12 healthy people (Michnovicz et al. 1991). Furthermore, in female mice prone to developing breast cancer the natural substance reduced the incidence of cancer and the number of tumors significantly. The natural substance was indole-3-carbinol (I3C).

Indole-3-carbinol (I3C) is a phytochemical isolated from cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, turnips, kale, green cabbage, mustard seed, etc.). I3C given to 17 men and women for 2 months reduced the levels of strong estrogen, and increased the levels of weak estrogen. But more importantly, the level of an estrogen metabolite associated with breast and endometrial cancer, 16--a-hydroxyestrone, was reduced by I3C (Bradlow et al. 1991).

When I3C changes "strong" estrogen to "weak" estrogen, the growth of human cancer cells is inhibited by 54-61% (Telang et al. 1997). Moreover, I3C provoked cancer cells to self-destruct (kill themselves via apoptosis). Induction of cell death is an approach to suppress carcinogenesis and is the prime goal of cytotoxic chemotherapy. The increase in apoptosis induced by I3C before initiation of new tumor development may contribute to suppression of tumor progression. Nontoxic I3C can reliably facilitate apoptosis (12 week treatment in rats); thus, this phytonutrient may become a standard adjunct in the treatment of breast cancer (Zhang et al. 2003)

I3C inhibits human breast cancer cells (MCF7) from growing by as much as 90% in culture; growth arrest does not depend on estrogen receptors (Cover et al. 1998). Furthermore, I3C induces apoptosis in tumorigenic (cancerous) but not in nontumorigenic (non-cancerous) breast epithelial cells (Rahman et al. 2003).

I3C does more than just turn strong estrogen to weak estrogen. 16-a-Hydroxyestrone (16-OHE) and 2-hydroxyestrone (2-OHE) are metabolites of estrogen in addition to estriol and estradiol. 2-OHE is biologically inactive, while 16-OHE is biologically active; that is, like estradiol, it can send "growth" signals. In breast cancer, the dangerous 16-OHE is often elevated, while the protective 2-OHE is decreased. Cancer-causing chemicals change the metabolism of estrogen so that 16-OHE is elevated. Studies show that people who take I3C have beneficial increases in the "weak" estriol form of estrogen and also increases in protective 2-OHE.

African-American women who consumed I3C, 400 mg for 5 days, experienced an increase in the "good" 2-OHE and a decrease of the "bad" 16-OHE. However, it was found that the minority of women who did not demonstrate an increase in 2-OHE, had a mutation in a gene that helps metabolize estrogen to the 2-OHE version. Those women had an eight times higher risk of breast cancer (Telang et al. 1997).


I3C Stops Cancer Cells from Growing
Tamoxifen is a drug prescribed to reduce breast cancer metastases and improve survival. I3C has modes of action similar to tamoxifen. I3C inhibited the growth of estrogen-receptor-positive breast cancer cells by 90% compared to 60% for tamoxifen. The mode of action attributed to I3C's impressive effect was interfering with the cancer cell growth cycle. Adding tamoxifen to I3C gave a 5% boost (95% total inhibition) (Cover et al. 1999).

In estrogen-receptor-negative cells, I3C stopped the synthesis of DNA by about 50%, whereas tamoxifen had no significant effect. I3C also restored p21 and other proteins that act as checkpoints during the synthesis of a new cell. Tamoxifen showed no effect on p21. Restoration of these growth regulators is extremely important. For example, tumor suppressor p53 works through p21 that I3C restores. I3C also inhibits cancers caused by chemicals. If animals are fed I3C before exposure to cancer-causing chemicals, DNA damage and cancer are virtually eliminated (Cover et al. 1999).

A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results are seen in the liver (Devanaboyina et al. 1997). Female smokers taking 400 mg of I3C significantly reduced their levels of a major lung carcinogen. Cigarette chemicals are known to adversely affect estrogen metabolism (Taioli et al. 1997).

There is no proven way to prevent breast cancer, but the best and most comprehensive scientific evidence so far supports phytochemicals such as I3C (Meng et al. 2000). The results from a placebo-controlled, double-blind dose-ranging chemoprevention study on 60 women at increased risk for breast cancer demonstrated that I3C at a minimum effective dosage 300 mg per day is a promising chemopreventive agent for breast cancer prevention (Wong et al. 1997). The results of a single-blind phase I trial which studied the effectiveness of I3C in preventing breast cancer in nonsmoking women who are at high risk of breast cancer are awaited. The rationale for this study is that I3C, ingested twice daily, may be effective at preventing breast cancer.

I3C was found to be superior to 80 other compounds, including tamoxifen, for anticancer potential. Indoles, which down-regulate estrogen receptors, have been proposed as promising agents in the treatment and prevention of cancer and autoimmune diseases such as multiple sclerosis, arthritis, and lupus. Replacement of all the chemically altered estrogen drugs, such as tamoxifen, with a new generation of chemically altered indole drugs that fit in the aryl-hydrocarbon (Ah) receptor and regulate estrogen indirectly may prove beneficial to cancer patients (Bitonti et al. 1999). An I3C tetrameric derivative (chemically derived) is currently a novel lead inhibitor of breast cancer cell growth, considered a new, promising therapeutic agent for both ER+ and ER- breast cancer (Brandi et al. 2003).

A summary of studies shows that indole-3-carbinol (I3C) can:

a)Increase the conversion of estradiol to the safer estriol by 50% in healthy people in just 1 week (Michnovicz et al. 1991)

b)Prevent the formation of the estrogen metabolite, 16,alpha-hydroxyestrone, that prompts breast cancer cells to grow (Chen et al. 1996), in both men and women in 2 months (Michnovicz et al. 1997)

c)Stop human cancer cells from growing (54-61%) and provoke the cells to self-destruct (apoptosis) (Telang et al. 1997)

d)Inhibit human breast cancer cells (MCF7) from growing by as much as 90% in vitro (Ricci et al. 1999)

e)Inhibit the growth of estrogen-receptor-positive breast cancer cells by 90%, compared to tamoxifen's 60%, by stopping the cell cycle (Cover et al. 1999)

f)Prevent chemically induced breast cancer in rodents by 70-96%. Prevent other types of cancer, including aflatoxin-induced liver cancer, leukemia, and colon cancer (Grubbs et al. 1995)

g)Inhibit free radicals, particularly those that cause the oxidation of fat (Shertzer et al. 1988)

h)Stop the synthesis of DNA by about 50% in estrogen-receptor-negative cells, whereas tamoxifen had no significant effect (Cover et al. 1998)

i)Restore p21 and other proteins that act as checkpoints during the synthesis of a new cancer cell. Tamoxifen has no effect on p21 (Cover et al. 1998)

j)Virtually eliminate DNA damage and cancer prior to exposure to cancer-causing chemicals (in animals fed I3C) (Grubbs et al. 1995)

k)Reduce DNA damage in breast cells by 91% (Devanaboyina et al. 1997)

l)Reduce levels of a major nitrosamine carcinogen in female smokers (Taioli et al. 1997)

How to Use I3C
While the evidence is compelling, it is too soon to know exactly how effective I3C will be as an adjuvant breast cancer therapy (see the Breast Cancer References for citations pertaining specifically to I3C).

Suggested dosage: Take one 200-mg capsule of I3C twice a day, for those under 120 pounds. For those who weigh more than 120 pounds, three 200-mg capsules a day are suggested. Women who weigh over 180 pounds should take four 200-mg I3C capsules a day.

Note: A little is good; a lot is not necessarily better. Too much I3C can have the opposite effect; therefore, do not exceed the suggested dosage.

Caution: Pregnant women should not take I3C because of its modulation of estrogen. I3C appears to act both at the ovarian and hypothalamic levels, whereas tamoxifen appears to act only on the hypothalamic-pituitary axis as an anti-estrogen. Both I3C and tamoxifen block ovulation by altering preovulatory concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) (Gao et al. 2002). The reported aversion to cruciferous vegetables by pregnant women may be associated with their ability to change estrogen metabolism. Estrogen is a necessary growth factor for the fetus.


Curcumin
Curcumin is extracted from the spice turmeric and is responsible for the orange/yellow pigment that gives the spice its unique color. Turmeric is a perennial herb of the ginger family and a major component of curry powder. Chinese and Indian people, both in herbal medicine and in food preparation, have safely used it for centuries.

Curcumin has a number of biological effects in the body. However, one of the most important functions is curcumin's ability to inhibit growth signals emitted by tumor cells that elicit angiogenesis (growth and development of new blood vessels into the tumor).

Curcumin inhibits the epidermal growth factor receptor and is up to 90% effective in a dose-dependent manner. It is important to note that while curcumin has been shown to be up to 90% effective in inhibiting the expression of the epidermal growth factor receptor on cancer cell membranes, this does not mean it will be effective in 90% of cancer patients or reduce tumor volume by 90%. However, because two-thirds of all cancers overexpress the epidermal growth factor receptor and such overexpression frequently fuels the metastatic spread of the cancer throughout the body, suppression of this receptor is desirable.

Other anticancer mechanisms of curcumin include:

a)Inhibition of the induction of basic fibroblast growth factor (bFGF). bFGF is both a potent growth signal (mitogen) for many cancers and an important signaling factor in angiogenesis (Arbiser et al. 1998).

b)Antioxidant activity. In vitro it has been shown to be stronger than vitamin E in prevention of lipid peroxidation (Sharma 1976; Toda et al. 1985).

c)Inhibition of the expression of COX-2 (cyclooxygenase 2), the enzyme involved in the production of prostaglandin E2 (PGE-2), a tumor-promoting hormone-like agent (Zhang et al. 1999).

d)Inhibition of a transcription factor in cancer cells known as nuclear factor-kappa B (NF-KB). Many cancers overexpress NF-KB and use this as a growth vehicle to escape regulatory control (Bierhaus et al. 1997; Plummer et al. 1999).

e)Increased expression of nuclear p53 protein in human basal cell carcinomas, hepatomas, and leukemia cell lines. This increases apoptosis (cell death) (Jee et al. 1998).

f)Increases production of transforming growth factor-beta (TGF-beta), a potent growth inhibitor, producing apoptosis (Park et al. 2003; Sporn et al. 1989).

g)TGF-beta is known to enhance wound healing and may play an important role in the enhancement of wound healing by curcumin (Mani H et al. 2002; Sidhu et al. 1998).

h)Inhibits PTK (protein tyrosine kinases) and PKC (protein kinase C). PTK and PKC both help relay chemical signals through the cell. Abnormally high levels of these substances are often required for cancer cell signal transduction messages. These include proliferation, cell migration, metastasis, angiogenesis, avoidance of apoptosis, and differentiation (Reddy et al. 1994; Davidson et al. 1996).

i)Inhibits AP-1 (activator protein-1) through a non-antioxidant pathway. While curcumin is an antioxidant (Kuo et al. 1996), it appears to inhibit signal-transduction via protein phosphorylation thereby decreasing cancer-cell activity, regulation, and proliferation (Huang et al. 1991).
Based on the favorable, multiple mechanisms listed above, higher-dose curcumin would appear to be useful for cancer patients to take. However, as far as curcumin being taken at the same time as chemotherapy drugs, there are contradictions in the scientific literature. Therefore, caution is advised. Please refer to the Cancer Chemotherapy protocol before considering combining curcumin with chemotherapy.

Curcumin's effects are a dose dependent response, and a standardized product is essential. The recommended dose is four 900-mg capsules 3 times per day, preferably with food.