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Natural Alternatives to Tamoxifen for Breast Cancer

See also Carahealth Anticancer

As reported on Monday, 28 March 2011 on the BBC news a panel of experts have reported in the Lancet Oncology that drugs such as tamoxifen could reduce the chances of developing breast cancer.

Tamoxifen of course is a powerful drug with side-effects. So women would need to think carefully before deciding whether they wanted to take the treatment long-term and look at alternatives such as dietary lifestyle changes that reduce breast cancer risk.

According to Professor Jack Cuzick, an epidemiologist at Queen Mary, University of London, "For every 1,000 women on tamoxifen for 10 years, we estimate there would be 20 fewer breast cancers. But there would be three more womb cancers and six more deep vein thromboses."

So a key factor will be identifying women who are at increased risk of breast cancer. Among measures already taken into account are family history and increasing age. The researchers say increased breast density, visible on mammograms, could also be a useful assessment tool. There are other factors which affect a woman's lifetime risk such as reproductive history and issues such as bodyweight, physical activity and alcohol intake. Tamoxifen is currrently not licensed as a preventive therapy and this report calls for Tamixifen to be licenced as a preventive treatment.

What is Tamoxifen?

Tamoxifen is an oestrogen receptor antagonist therfore blocks oestrogen receptors to from cancer promoting oestrogen in breast tissue. In the endometrium, tamoxifen is an oestrogen agonist, therofre promotes cancer causing oestrogen therefore increasing the risk of endometrial cancer. It has been the standard anti-oestrogen therapy for hormone receptor positive early breast cancer.

Side effects

Positive side effects

Bone

A beneficial side effect of tamoxifen is that it prevents bone loss by acting as an oestrogen receptor agonist (i.e., mimicking the effects of oestrogen) in this cell type. As oestrogen stimulates the osteoclasts (bone building cells) and inhibits the ostoeclasts (bone destroying cells), it prevents osteoporosis.

Negative side effects

Endometrial cancer

Tamoxifen is known as a selective oestrogen receptor modulator. Even though it is an antagonist in breast tissue (blocks oestrogen), it acts as partial agonist (oestrogen promoter) on the endometrium and has been linked to endometrial cancer. Risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for 5 years. Tamoxifen is listed as a known carcinogen, stating that it increases the risk of some types of uterine cancer while lowering the risk of breast cancer recurrence.The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

Cardiovascular and metabolic

Tamoxifen treatment of postmenopausal women is associated with beneficial effects on serum lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect. For some women, tamoxifen can cause a rapid increase in triglycerides and increased risk of thromboembelism.Tamoxifen is also a cause of fatty liver.

Central nervous system

Tamoxifen treated breast cancer patients show evidence of reduced cognition and memory. A significant number of tamoxifen treated breast cancer patients experience a reduction in libido.

Whats the Natural Alternative to Tamoxifen?

There are a number of compounds found naturally in foods and herbs that block the action of cancer promoting oestrogen and naturally reduces the risk of breast cancer. Currently the western medical approach to breast cancer is as follows;

  • Surgery
  • Chemotherapy
  • Radiotherapy
  • Drugs including;

As some breast cancer cells require oestrogen to grow, eliminating oestrogen suppresses their growth. Drugs are aimed at suppressing oestrogen production and also blocking its effect.

1. Tamoxifen

As mentioned above, Tamoxifen is is an oestrogen receptor blocker

2. Aromadex (Anastrozole)

Aromadex is an aromatase inhibitor, which means that it interrupts a critical step in the body's synthesis of oestrogen.

3. Herceptin (Trastuzumab)

Herceptin is an antibody that interferes with the HER2 receptor.Antibodies are molecules from the immune system that bind selectively to different proteins. Herceptin is an antibody that binds selectively to the HER2 protein. When it binds to defective HER2 proteins, the HER2 protein no longer causes cells in the breast to reproduce uncontrollably. This increases the survival of people with cancer. However, cancers usually develop resistance to Herceptin. The HER receptors are embedded in the cell membrane and communicate signals from outside the cell to inside the cells and turn genes on and off. The HER receptors regulate cell growth, survival, adhesion, migration and differentiation and are implicated in some cancers, most notably breast cancers.

In breast cancer, HER2 is over-expressed, and, among other effects, causes breast cells to reproduce uncontrollably. From a naturopathic perspective the idea is to match the pharmacological action of drugs with natural alternatives to effectively reduce the risk of breast cancer without any negative side effects. As you will see though, natural medicine contains an arsenal of anticancer compounds which act to address all the causes of cancer.

4. Tyrosine kinase receptor inhibitors

Tyrosine kinase inhibitors (TKI) represent a growing class of anti-cancer agents.

"A growing body of clinical data is now available to support the clinical effectiveness of GSK's Tykerb (lapatinib ditosylate) in advanced breast cancer."

It is estimated that about 30% of the current effort of the pharmaceutical industry is devoted to the development of protein kinase inhibitors, especially tyrphostins/TKIs. Read more about the mechanism of TKIs and the natural alternatives to TKIs below.

The naturopathic causes of breast cancer

1. Oestrogen excess

2. Excess aromatase activity

3. Excess betaglucuronidase activity

4. Excess activity of cytochrome P450 enzymes

5. Excess Insulin Like Growth Factor (IGF)

6. Excess inflammatory mediators including Cox and Lox, IL6 and TNF alpha

For a full naturopathic explanation of the causes of cancer please see also Naturopathic Causes and Treatment of Cancer

Natural Tamoxifen, Aromadex (Arimidex) and Herceptin and more

Natural Tamoxifen

Phytoestrogens

Phytoestrogens, also known as xenoestrogens (foreign substances) are not generated within the endocrine system but consumed by eating plants rich in nonsteroidal plant compounds. Because of their structural similarity with oestrogen, they have the ability to stimulate oestrogen receptors in the cases of oestrogen deficiency or block oestrogen receptors in the case of oestrogen excess. Phytoestrogens work in the same way as Tamoxifen to either block or stimlaute oestrogen depending on the tissue but without the unwanted side effects. Phytoestrogens have protective action against a wide range of health disorders including prostate, breast, bowel and other cancers, cardiovascular disease, brain function disorders, osteoporosis and menopause.

Food sources of phytoestrogens

Flax seed and other oilseeds contain the highest total phytoestrogen content, followed by soybeans and tofu. The highest concentrations of isoflavones are found in soybeans and soybean products followed by legumes, whereas lignans are the primary source of phytoestrogens found in nuts and oilseeds (e.g. flax) and also found in cereals, legumes, fruits and vegetables.

A more comprehensive list of foods known to contain phytoestrogens includes:

  • soybeans
  • tofu
  • tempeh
  • soy beverages miso
  • kudzu root
  • linseed (flax)
  • sesame seeds
  • wheatberries
  • fenugreek
  • oats
  • barley
  • dried beans, kidney, lima, blackbeans, pinto etc
  • lentils
  • yams
  • rice
  • alfalfa
  • mung beans apples
  • carrot
  • pomegranates
  • wheat germ
  • rice bran
  • soy linseed bread
  • ginseng
  • hops
  • fennel
  • anise

Aromadex (Arimidex)

Aromatase is a cytochrome P450 enzyme. Aromatase is a very important pharmacological target, particularly for the treatment of breast cancer. Before menopause, the ovaries are the major sites of oestrogen production. In postmenopausal women, oestrogen is produced by a process called aromatization which occurs mostly in adipose (fat) tissue. The adrenal androgens DHEA is also aromatised into oestrogen. Aromatase is an enzyme that converts weak oestrogen to cancer promoting oestrogen in adipose (fat) tissue. Aromatase is overactive in obesity so weight loss is advisable. Aromatse inhibitor drugs are also prescribed for prostate cancer.

The drug Aromadex is an aromatase inhibitor . Aromatase inhibitors block the synthesis of oestrogen. This lowers the oestrogen level, and slows the growth of cancers, but like any drug, Aromadex has side effects. There are many natural aromatase inhibitors that have no unwanted side effects.

Side effects of Aromatase inhibitor drugs

Bone loss

Breast and prostate cancer treatment can lead to bone loss and increase the risk for osteoporosis and fractures. Breast cancer patients treated with aromatase inhibitors are more likely to have bone loss and fractures. Similarly, men who received androgen deprivation therapy to treat their prostate cancer had an increased risk of bone disorders.

Natural Aromadex (Arimimdex)  Aromatase inhibitors

Resveratrol

Resveratrol is natural phenol, produced by several plants when under attack by pathogens such as bacteria or fungi that has anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects of resveratrol have been reported.

Resveratrol is found in the skin of red grapes and in other fruits. Red wine contains a high level of it.

Oleuropein

Oleuropein is a chemical compound found in olive leaf from the olive tree. Oleuropein and its metabolite hydroxytyrosol have powerful antioxidant activity and give extra-virgin olive oil its bitter, pungent taste. Oleuropein strengthens the immune system and enhances thermogenesis by increasing the thermogenin content in brown adipose tissue and the secretion of noradrenaline and adrenaline.

Quercetin

Quercetin is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. Several laboratory studies show quercetin may have anti-inflammatory and antioxidant properties.

Foods rich in quercetin include;

  • black and green tea (Camellia sinensis; 2000–2500 mg/kg),
  • capers
  • lovage
  • apples
  • onion, especially red onion (higher concentrations of quercetin occur in the outermost rings),
  • red grapes
  • citrus fruit
  • tomato
  • broccoli and other leafy green vegetables
  • Berries including; raspberry, bog whortleberry, lingonberry, cranberry, chokeberry, sweet rowan, rowanberry, sea buckthorn berry, crowberry
  • prickly pear cactus

Organic vegetables have been showed to cntain significantly more quercetin than their conventional counterparts.

Chrysin

Chrysin is a naturally occurring flavanoid. Chrysin is an aromatase inhibitor, decreasing the levels of oestrogen in the body.

Food sources of Chrysin

  • passion flower
  • Honeycomb

Naringenin

Naringenin is a flavanone, a type of flavonoid, that is considered to have a bioactive effect on human health as antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator.

Food sources of naringenein

  • Grapefruit. It is the predominant flavanone in grapefruit.
  • Oranges
  • Tomato (skin).
  • Naringenin can be absorbed from cooked tomato paste.

Apigenin

Apigenin is a citrus bioflavonoid. Apigenin, like most flavonoids, has antioxidant, anti-inflammatory and antitumour properties. Apigenin is commonly recognised as to mediate at least part of the chemopreventive action of vegetables and fruits in the cancerous process. Recently it was shown that Apigenin induces a process called autophagia (a kind of cellular dormancy) which may well explain it chemopreventive properties but at the same time induces resistance against chemotherapy. Apigenin is a potent inhibitor of CYP2C9, an enzyme responsible for the metabolism of many pharmaceutical drugs in the body so avoid if taking a supplement if on medication. Natural foods sources are safe.

Food sources of apegenin

  • Parsley
  • Celery
  • Dandelion root coffee
  • Thyme
  • Peppermint
  • Chamomile
  • Horsetail
  • Lemon balm
  • Perilla
  • Vervain
  • Yarrow
  • Red wine
  • Tomato sauce

Genistein and diadzein

Genistein and diadzein are isoflavones.

Besides functioning as antioxidant and anthelmintic, many isoflavones have been shown to interact with oestrogen receptors/ Isoflavones also produce non-hormonal effects.

Food sources of Isoflavones inc genestein and diadzein

  • lupin
  • fava beans
  • soybean
  • chickpeas
  • kudzu
  • psoralea being the primary food source
  • also in the medicinal plant, Flemingia vestita
  • Coffee

Lets go one step further than western medicine

Excess Betaglucuronidase Activity

Betaglucuronidase is a bowel enzyme that reconjugates weak oestrogen into strong cancer promoting oestrogen. Like aromatase, is also a causative factor in oestrogen dependent breast cancers. Currently there is no drug aimed at inhibiting excess betaglucuronidase activity. Natural medicine however, has specific compounds that reduce betaglucuronidase activity and naturally reduce the risk of breast cancer without the unwanted side effects.

Natural Betaglucuronidase inhibitors

Calcium D-glucarate

Calcium D-glucarate is the calcium salt of D-glucaric acid, a natural substance found in many fruits and vegetables. Calcium D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme found in certain bacteria that reside in the gut. Betaglucuronidase recongugates weak oestrogens into harmful cancer promoting oestrogen.

Foods sources high in glucaric acid (a form of calcium D-glucarate) include;

  • apples
  • brussels sprouts
  • broccoli
  • cabbages
  • bean sprouts
  • scutellaria baicalensis

Natural Cytochrome P450 enzyme inhibitors

Excess activity of cytochrome P450 enzymes are also a causative factor of breast cancer. Cytochrome P450 enzymes oxidize compounds which can cause mutation and induce cancer development. Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including oestrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism.

Cytochrome P450 enzymes also function to metabolise toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

Glucosinolate and its' metabolites, Isothiocyanate and Indole 3 carbinol

Natural isothiocyanates are produced by enzymatic conversion of metabolites called glucosinolates which occur as secondary metabolites of Brassicacae family also known as cruciferous vegetables. Isothiocyanates are responsible for the typical flavour of these vegetables. Isothiocyanates and sulphoraphane, have been shown to inhibit carcinogenesis and tumorigenesis and as such are useful chemopreventive agents against the development and proliferation of cancers. Glucosinolates work on a variety of levels, the most notably being that they inhibit cancer by inhibiting cytochrome P450 enzymes, to reduce oxidization and therfore mutation and cancer development.

Isothiocyanates and glucosinolates summary

  • Isothiocyanates are derived from the hydrolysis (breakdown) of glucosinolates—sulphur-containing compounds found in cruciferous vegetables.
  • Cruciferous vegetables contain a variety of glucosinolates, each of which forms a different isothiocyanate when hydrolysed.
  • Isothiocyanates, such as sulphoraphane, may help prevent cancer by promoting the elimination of potential carcinogens from the body and by enhancing the transcription of tumour suppressor proteins.
  • Epidemiological studies provide evidence that human exposure to isothiocyanates through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation in the metabolism and elimination of isothiocyanates from the body.
  • Glucosinolates are present in relatively high concentrations in cruciferous vegetables, but cooking, particularly boiling and microwaving at high power, may decrease the bioavailability of isothiocyanates.

Dietary sources of isothyocyanates

  • horseradish
  • land cress
  • Ethiopian mustard
  • kale
  • collard greens
  • Chinese broccoli kai-lan
  • cabbage
  • brussels sprouts
  • kohlrabi
  • broccoli
  • broccoflower
  • broccoli
  • romanesco cauliflower
  • wild broccoli
  • bok choy (pak choy)
  • komatsuna
  • mizuna
  • Rapini (broccoli rabe)
  • Brassica rapa parachinensis
  • flowering cabbage
  • Chinese cabbage
  • napa cabbage
  • turnip root; greens
  • rutabaga
  • Siberian kale
  • canola/rapeseed
  • wrapped heart mustard cabbage
  • white and black mustard seeds
  • rocket
  • garden cress
  • watercress
  • radish
  • daikon
  • wasabi

Indole-3-carbinol

Indole-3-carbinol is produced by the breakdown of the glucosinolate glucobrassicin, which can be found at relatively high levels in cruciferous vegetables. Indole-3-carbinol is the subject of on-going research into its anticarcinogenic, antioxidant and anti-atherogenic effects. Indole-3-carbinol and cancer In respect to the mechanism of their anticarconogenic properties, indole-3-carbinol has the ability to alter oestrogen metabolism and also display other cellular effects. Indole-3-carbinol induces a G1 growth arrest of human reproductive cancer cells. This is significant in the prevention and treatment of cancer, as the G1 phase of cell growth occurs early in the cell lifecycle, and, for most cells, is the major period of cell cycle during its lifespan.

Tyrosine kinase receptor inhibitors

Tyrosine kinase inhibitors (TKI) represent a growing class of anti-cancer agents. Protein tyrosine kinases are enzymes that provide a central switch mechanism in cellular signal transduction pathways. As such they are involved in many cellular processes such as cell proliferation, metabolism, survival and apoptosis. Several protein tyrosine kinases are known to be activated in cancer cells and to drive tumour growth and progression. Protein kinases can become mutated, stuck in the "on" position , and cause unregulated growth of the cell, which is a necessary step for the development of cancer therefore, kinase inhibitors are often effective cancer treatments. TKIs are typically used as anti-cancer drugs.

"A growing body of clinical data is now available to support the clinical effectiveness of GSK's Tykerb (lapatinib ditosylate) in advanced breast cancer."

Blocking tyrosine kinase activity therefore represents a rational approach to cancer therapy. Already several TKIs have been approved as anti-cancer agents. The erbB or HER family of transmembrane tyrosine kinase receptors, especially receptors erbB1 (or EGFR) and erbB2 (or Her2/neu), has been identified as an important therapeutic target in a number of cancers. Her2/neu, for example, is overexpressed in around 20% to 30% of patients with aggressive breast cancer, while EGFR is overexpressed in several solid tumours.

It is estimated that about 30% of the current effort of the pharmaceutical industry is devoted to the development of protein kinase inhibitors, especially tyrphostins/TKIs. Again all drugs have side effects and their are natural alternatives to TKIs.

Natural Alternatives to TKIs

These are known as anticancer or antiangiogneic foods. When we say a food is anticancer, what it actually means is that it is a natural Tyrosine Kinase Receptor inhibitor (TKI), therfore prevents angiognesis and the formation of new blood vessels to feed a tumour.

Natural Tyrosine Kinase Inhibitors

  • Catechins - Catechins, the main compounds of green tea leafs, have been identified as potent natural inhibitors of several RTKs.
  • Genestin - in soya (esp leukemic cells and breast cancer cells) Genistein produces cell cycle arrest and apoptosis
  • Apeginin - in chamomile
  • Curcumin - in turmeric
  • Diadzein - in soya
  • Epigallocatechin galate - in green tea
  • Hypericin - St Johns Wort
  • Artemisia annua (Chinese wormwood)
  • Viscum album (European mistletoe)
  • Scutellaria baicalensis (Chinese skullcap)
  • resveratrol and proanthocyanidin (grape seed extract, red wine)
  • Magnolia officinalis (Chinese magnolia tree)
  • Camellia sinensis (green tea)
  • Ginkgo biloba
  • Quercetin - see food sources above
  • Poria cocos (Fu Ling)
  • Zingiber officinalis (ginger)
  • Panax ginseng
  • Rabdosia rubescens hora (Rabdosia) and other Chinese destagnation herbs.

Insulin Like Growth Factor (ILGF)

ILGF is a polypeptide hormone which is naturally in cows milk and breast milk. It is anabolic. It is implicated for breast, endometrial, ovarian, prostate and other hormone linked cancers. ILGF is a potent activator of TKI signalling pathways (see above). These are enzymes responsible for the production of new blood vessels required by a growing tumour (angiogenesis). IGF-1 plays a role in cell proliferation and apoptosis and is mitogenic. It binds specifically to IGF-1 receptor, which is a TKI.

Natural ILGF Inhibitors

  • Tomatoes
  • soya polyphenols
  • vegan diet (due to its low protein content).
  • Barley is highest in chromium which lowers blood sugar therfore lower both insulin and ILGF.
  • If you have breast cancer avoid milk as it increases ILGF

HER2

HER2 is a term used in the diagnosis of breast cancers and is an indicator that your cancer is more virulent. HER2 is member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. It is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation. It is known as an oncogene. An oncogene turns on cancer.

It works in combination with ILGF.

ILGF + HER2 => Increases TKIs / employs COX2 => angiogenesis (a step in transition of tumour from dormant to malignant)

Cox and Lox (and fox in sox)

Cox (cyclooxygenase) and Lox (lipoxygenase) are two enzymes invloved in inflammation. Cox and Lox are overexpressed in tumours. Excess inflammation is implicated in the formation of cancer as it causes cell damage and genetic mutation increasing the chance of cancer formation. Cox and Lox are also employed by oncogenes such as HER2. Following an anitiflammatory diet that includes liberal amounts of compounds that naturally inhibit Cox and Lox will decreases inflammation and cancer formation. When we say a food is anti-inflammatory what we mean is that is is a natural Cox and/or Lox inhibitor.

Natural Cox & Lox inhibitors

Natural Cox 2 inhibitors

  • Apigenin tea, numerous sources <40 uM Baicalein scute (huangqin)
  • Berberine phellodendron (huangbai)
  • Curcumin turmeric (jianghuang)
  • Eicosapentaenoic acid garlic (dasuan)
  • Evodiamine and evodol evodia (wuzhuyu)
  • Oleanolic acid numerous rosemary
  • Quercetin numerous
  • Resveratrol hu-chang (huzhang
  • Rutaecarpine evodia (wuzhuyu)
  • Ursolic acid ligustrum (nuzhenzi)
  • rosemary

Natural Lox 2 inhibitors

  • Allicin garlic (dasuan)
  • Berbamine hu-chang (huzhang)
  • Berberine coptis (huanglian)
  • Phellodendron (haungbai)
  • Boswellic acid frankincense (ruxiang)
  • Caffeic acid taraxacum (pugongying) dandelion
  • Epicatechin tea
  • Epicatechin-gallate tea
  • Epigallocatechin tea
  • Fisetin chih-shih (zhishi)
  • Flavone numerous
  • Galangin galanga (liangjiang)
  • Morin morus (sangbaipi)
  • Quercetin numerous
  • Theaflavin digallate tea
  • Ursolic acid ligustrum (nuzhenzi)

TNF alpha

Tumor necrosis factor-alpha is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumourigenesis, and viral replication. Its primary role is in the regulation of immune cells. Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases, as well as cancer.

Natural TNF Inhibitors:

  • Curcumin (in turmeric)
  • Catechins (in green tea)
  • Aucubin (in plantain) You can juice this common garden weed.

IL6

IL6 is also high in patients with cancer and involved in tumourigenesis.

Natural IL6 inhibitors

  • Aucubin - in plantain Aucubin inhibits IL6 and TNF-ά
  • Oestrogen inhibits IL6.

For a herbal formula designed specifically to address all the causes of breast cancer and other hormone dependant cancers, please see also Carahealth Anticancer

Carina is available to lecture for your group or institution on this subject.

Carina Harkin BHSc.Nat.BHSc.Hom.BHSc.Acu. is a practitioner of 11 years, complementary medicine lecturer of 4 years and mother of six in Galway, Ireland who practices what she teaches.

For an appointment call Carina directly on 083 34 66 333.

All products are available through www.carahealth.ie. Remember, we are here for a good time not a long time, enjoy your food life!

Carahealth Galway Ireland. Acupuncture, Naturopathy, Homeopathy, Herbal Medicine, Nutrition, Nutritional Therapy, Flower Essences, Iridology, Short Courses, Cosmetic Acupuncture

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