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Letrozole, Femara


This chemotherapy and cancer drugs article is about Letrozole (Femara) which 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. Letrozole is an aromatase inhibitor, which works by reducing the total amount of oestrogen in the body (circulating oestrogen levels), thereby limiting the amount of oestrogen that can affect breast cancer cells. 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.

Readers may also like to read our article Oestrogen - the killer in our midst, which gives information on the causes of excess oestrogen, and tips on how to combat it naturally. To go to the article - click here.)

Side effects can include: nausea and vomiting, tiredness and headaches, muscular aches and joint pain, hot flushes, difficulty breathing and hair thinning (see above for long-term risk).

Article on Aromatase Inhibitors:  

Why not read our overview of your cancer? Click here.

Women with breast cancer, and even some of those who want to prevent breast cancer, will know of the Holy Trinity: Tamoxifen, Aromatase Inhibitors and Herceptin the ´chemotherapy´ drugs that can fight breast cancer; the drugs that can help a woman beat breast cancer.


Oestrogen and progesterone can each drive some breast cancers.  Tests will be conducted to find out whether you are reacting to either of these hormones and, if so, hormone therapy will then be prescribed.


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 mutations. Oestrogen is the female sex hormone, but it is not a single entity; more it exists in a family of forms, some dangerous, others far less so. You can also absorb chemicals from some pesticides and in-home products that can act like oestrogen in your body.


You can find out far more about Oestrogen and cancer, and ways of naturally combating it in our article ´Pillar II Toxins and Oestrogen´, one of our ´4 Pillars of cancer´.



Aromatase inhibitors (AI´s) aim to block the production of oestrogen in your body in the first place. These include Anastrozole (Arimidex); Exemestane (Aromasin) and Letrozole (Femara).  Oestrogen is principally made in the ovaries pre-menopause, but up to 60 per cent of it can be made in other tissues. Thus AI´s are most often used in women who have reached menopause.


Finally, much work is being done on women who are neither oestrogen positive (ER+) or Progesterone positive (P+). One breakthrough was finding a group of women (about 20 per cent in total) who were HER-2 positive. About half of these respond positively to a monoclonal antibody called Herceptin.


For your information, Tamoxifen is used to block the action of oestrogen on both healthy cells and cancer cells.


Newer work is focussing on PARP inhibitors for women who are not any of the above, and on drugs to kill cancers caused by stem cell developments, and more.


But for this piece we just focus on AI´s.


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 vitamin D survive far longer than those with deficiencies. And women who take daily exercise double their survival rates.


Aromatase Inhibitors (AI´s)


Approximately two in three breast cancers rely on oestrogen to grow. Oestrogen is the female sex hormone commonly understood to be produced in the ovaries. At menopause the oestrogen production in the ovaries declines just enough to stop egg production - the total oestrogen level in the body falls by about one third.


However, women do produce oestrogen elsewhere in the body; a source of the precursors being fat. In post-menopausal women oestrogens are mainly produced in the adrenal glands fatty tissues, or in muscle and within the fatty layers under the skin. These are termed endogenous oestrogens.


The production mechanism is carried out by an enzyme called aromatase and the conversion process is known as aromatisation. AI´s thus work by blocking oestrogen synthesis and they reduce oestrogen in post-menopausal women to very low levels.


Of course, you can have external chemicals in your body, for example from certain pesticides, BPA, phthalates, toluene, perfumes, parabens etc which are known to act like oestrogens they are termed xenoestrogens and are exogenous oestrogens. Some of them can be just as harmful as the more aggressive natural oestrogens.


An oestrogen-positive female with breast cancer may typically have five years of tamoxifen followed by three years of an Aromatase Inhibitor. The makers of AI´s have questioned this and, unsurprisingly, there have been studies to show that AI´s can be used much earlier in the treatment pattern. NICE now recommends AI´s for early stage breast cancer too.


Cutting oestrogen production to very low levels is obviously an extreme measure. There are many ways of cutting both natural endogenous, and chemical exogenous oestrogens.


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. 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 (For our article Click here), as is the hormone Melatonin (click here), produced about 90 minutes after falling asleep in a darkened room.


Readers should also look at our article ´Aromatase Inhibitors are there natural alternatives to the drugs?´


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.


There are 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.


Other articles of interest:



Red Clover


´Aromatase Inhibitors are there natural alternatives to the drugs?´

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.

To return to the drug list, click here.

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