This patient-friendly article is about chemotherapy drug, Anastrozole (Arimidex) and Oestrogen which is an aromatase inhibitor (AI), a cancer drug licensed for use with post-menopausal women who have oestrogen-positive breast cancer; taken by mouth and may be used in combination with other drugs; it is most usually termed 'Hormone Therapy'.
Approximately 75%-80% of female breast cancers rely on oestrogen to grow. Oestrogen drives the proliferation of ER positive cancer cells. There are two main human estrogens - oestrone (estrone) and oestradiol (estradiol) made in the ovaries, adrenals, liver and fat stores by aromatase enzymes from androgens and adipose tissue (1).
Where a woman is premenopausal, oncologists will provide the drug Tamoxifen to block the estrogen receptor sites on all the cells in the body.
Once a woman is post-menopausal, oestrogen production by the ovaries has declined significantly, and so the primary issue is to cut the production of oestrogen in the peripheral tissues. Post-menopausal women's main source of oestrogen is through the conversion of androgens (sex hormones produced by the adrenal glands) into oestrogens. This is carried out by an enzyme called aromatase.
This conversion process is known as aromatisation and happens mainly in the fatty tissues of the body, although it can happen for example in the liver. Hence the use of drugs that can inhibit aromatase enzymes. Aromatase Inhibitors do not work in the ovaries.
Anastrozole and rival drug Letrozole both work by blocking oestrogen synthesis. They reduce the level of oestrogen in post-menopausal women to very low levels. But there can be severe long-term side-effects to this, for example, brittle bones, and there is a school of thought that believes natural progesterone is a better alternative as it is accepted by the receptor sites and opposes oestrogen in a natural way, without the serious side-effects. A drawback of natural progesterone is that it doesn’t inhibit aromatase. It is therefore useful as a complementary treatment but has drawbacks as an alternative.
Side-effects of aromatase inhibitors can include: hot flushes and sweats, tiredness, vaginal dryness, nausea, and vomiting, diarrhoea, hair thinning, headaches, vaginal bleeding (very rare and usually in first few weeks of treatment), joint pains/stiffness and increased or decreased appetite. Some women just cannot tolerate AI drugs and come off them inside several months, while others stay on them for 5 years or even longer.
Long-term risk: osteoporosis; although bisphosphonates can be given to prevent bone loss.
Cancer Research UK was conducting a 10-year-study using anastrozole on 10,000 post-menopausal women with a family history of breast cancer to see whether it could act as a preventative agent. In America it is already used as a preventative agent.
There are many ways that women (and men) can reduce their oestrogen levels naturally. This article is essential reading for any ER+ve woman with cancer:
Go to: 'Natural Aromatase Inhibitors'
On diagnosis, women with breast cancer and ovarian cancer will be tested to see if they are oestrogen positive. The 'score' in breast cancer is measured out of 8; and women will also be tested for Progesterone and HER2.
Oestrogen is known to drive many breast cancers by causing changes inside healthy cells, by causing stem cells to stay in this rapidly dividing state, and by even causing damaging epigenetic cellular mutations. Oestrogen is a family of chemicals with three main groups -
* Human oestrogen (for example, oestradiol and oestrone);
* Chemical oestrogen (xenoestrogens) for example, in herbicides, pesticides and many toiletry and personal care products such as perfumes, nail polishes and sun-creams); BPA, phthalates, toluene, perfumes, parabens etc which are known to act like oestrogen and are termed exogenous oestrogens. Some of them can be just as harmful as the the most aggressive human oestrogen.
* Plant oestrogen (phytoestrogen). Plant oestrogens are much, much weaker, wash through the body quickly and can only block the receptors from the action of human and chemical oestrogen temporarily. Plant oestrogens are your friends. Tests by Professor Trevor Powles showed that genistein could block receptors from attack by estradiol. Dr. Young S. Kim, head of nutrition and cancer at the National Cancer Institute lists genestein (from soy and Red Clover) in her top ten compounds for restricting cancer recurrence.
Go to: our article called Oestrogen - the killer in our midst
Aromatase inhibitors (AI’s)
AIs aim to block the production of oestrogen and include Anastrozole (Arimidex); Exemestane (Aromasin) and Letrozole (Femara).
One thing to remember is that drugs can’t do it all. Japanese women have been shown to have a much lower incidence of recurrence of breast cancer than Western women. Diet and lifestyle were the reasons given by the researchers (Int Radiation Oncol 2005; 62). Other research we have covered has signalled the importance of good levels of omega 3 and vitamin B-12. In a 2008 Study from the University of Toronto, women with good blood levels of plasma vitamin D survive far longer than those with deficiencies. And women who take daily exercise double their survival rates.
Being overweight is a counter-active factor as fat can provide the building blocks for oestrogen, and is also an excellent solvent and so will store both endogenous and exogenous oestrogens that you would be better to excrete.
Alcohol can enhance oestrogen production; grapefruit can stimulate aromatase enzymes as can low melatonin levels. Having good blood levels of plant oestrogens (phytoestrogens) has been shown to be protective, as has Indole3carbinol (from broccoli and greens. But one of the biggest factors in excreting excess oestrogen has now been shown in clinical trials to be the involvement of certain beneficial bacteria in the gut, and their ability to use whole foods like lignans to bind to (chelate with) oestrogenic products and help excrete them.
Natural Progesterone hormone is also an oestrogen ’balancer' as is the hormone Melatonin produced about 45 minutes after falling asleep in a darkened room. In America there is a growing trend amongst women who cannot tolerate AIs to switch to a Chinese Herbal mix called Myomin.
Side effects can typically include: hot flushes and sweats, tiredness, vaginal dryness, nausea, and vomiting, diarrhoea, hair thinning, headaches, vaginal bleeding (very rare and usually in first few weeks of treatment), joint pains/stiffness and increased or decreased appetite. Long-term risk: osteoporosis is the big worry although bisphosphonates can be given to prevent bone loss.
Here is a summary of the three commonly used AI’s:
* Anastrozole (Arimidex) is licensed for use on post-menopausal women with operable ER+ (oestrogen driven) breast cancer who cant take tamoxifen, for example due to problems with hot flushes or thrombo-embolism. In clinical trials it has proved more effective than Tamoxifen post-menopausally due to its general action on the various sources of endogenous oestrogens. Cancer Research UK is conducting a 10-year-study using anastrozole on 10,000 post-menopausal women with a family history of breast cancer to see whether it will prevent it.
Usage: It is taken orally.
* Exemestane (Aromasin) is an aromatase inhibitor used in the treatment of a breast cancer stimulated by the body’s oestrogen levels. Stopping the body’s own oestrogen reaching the tumour can cause the cancer cells to stop growing and in some cases shrivel up and die completely (self destruct - apoptosis). Exemestane effectively blocks the production of oestrogen from these sites.
Interim findings of the TEAM (Tamoxifen Exemestane Adjuvant Multicenter) trial reported on 11th December at the 2008 San Antonio Breast Cancer Symposium (SABCS) suggest women with early invasive breast cancer can expect fewer breast cancer recurrences and a longer time to the occurrence of distant metastases if they are treated with the exemestane rather than the standard adjuvant therapy tamoxifen after initial therapy (surgery plus chemotherapy and/or radiotherapy).
TEAM includes almost 10,000 postmenopausal women with invasive hormone-receptor-positive early breast cancer from nine countries.
* Letrozole (Femara) was approved by the FDA in 1997 to help treat advanced breast cancer in post-menopausal women whose breast cancer tumours have not responded well to Tamoxifen. Recent publication of a trial has shown that using Letrozole, after five years of Tamoxifen, is more effective than continuing Tamoxifen for women who have primary operable breast cancer.
Go to: 10 ways to improve your chemotherapy success and reduce side-effects
Reference
- Estrogen production and Action - https://www.ncbi.nlm.nih.gov/pubmed/11511861
Other articles that you may find interesting are:
- A diet for Chemotherapy
- Immunotherapy overview
- A to Z Guide to Complementary Therapies
Go to: Return to the CANCERactive drug list
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