Exemestane, or Aromasin - action and side-effects

Exemestane, or Aromasin - action and side-effects

Patient-friendly article on Exemestane (Aromasin), an aromatase inhibitor (AI), a cancer drug licensed for use in the treatment of advanced breast cancer, stimulated by oestrogen (estrogen) where tamoxifen has already been used; taken by mouth with food, it may be used in combination with other drugs; Exemestane is most usually termed 'Hormone Therapy'.

In a Lancet report (1) on a randomised phase III Clinical Trial (TEAM) of exemestane alone versus tamoxifen then exemestane (sequential group), the 5-year survival in the sequential group was 85%, whereas the exemestane alone group was 86%.

Clinical trials reported in 2011 showed that women at high risk of breast cancer developed less cancer at a 3-year follow up stage. The group taking exemestane were two thirds less likely to develop breast cancer (2).

Exemestane is a steroid, structurally similar to the substrate of aromatase.

Side effects of Exemestane - can include: fatigue, nausea or vomiting, hot flushes, decreased libido, joint pain, mild skin rashes, insomnia, headaches, depression, loss of bone density, loss of appetite, hair thinning, diarrhoea or constipation.  There are concerns over high blood pressure. 

Long-term risk: osteoporosis; although bisphosphonates can be given to prevent bone loss.

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 (3).

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.

AIs usually 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.

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

Here is a summary of the two other 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.

   * 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.

References

  1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext
  2. https://www.ncbi.nlm.nih.gov/pubmed/21639806
  3. Estrogen production and Action - https://www.ncbi.nlm.nih.gov/pubmed/11511861

Other articles that you may find interesting are:

  1. Diet for Chemotherapy ; 
  2. Beneficial bacteria ; 
  3. A-Z guide to complementary therapies
  4. Your cancer, where you can read about everything from causes to cancer treatments to complementary therapies for your cancer.
  5. How to boost your immune system.

Go to:  Return to the CANCERactive drug list

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